LIVE #DavaBreast — 2026 Kona Breast Cancer Summit: the full programme, session slides & faculty View Full Coverage →
Conference Intelligence · Fairmont Orchid, Kona, Hawaii · Aug 18–22, 2026

2026 Kona Breast Cancer Summit

DAVA Oncology's Hawaii breast cancer meeting, reconstructed from the published programme: 29 sessions and 162 podium talks across four days, with 265 captured slides pinned to the talk they came from. Captions are verbatim from the meeting feed.

29
Sessions
162
Podium Talks
265
Slides Captured
75
Faculty
39
Trials Named
75 on the podium · 26 on X

Faculty

Everyone who presented or moderated, A–Z by surname. Portraits come from the speaker's X profile where they have one, otherwise from the session title card DAVA showed before each block. Cards with a handle link straight to that X profile.

Yara AbdouYara Abdou@yabdoumd2 talksTaiwo AdesoyeTaiwo Adesoye@t_adesoyemd2 talks
PAPooja Advani3 talks · chairs 1
Karen AndersonKaren Anderson2 talks
MBMarija Balic2 talks
ABAndrew Brenner2 talks
Adam BrufskyAdam Brufsky@breastoncdoc4 talks · chairs 2Amina ChaudhryAmina Chaudhry@aminachaudhrymd2 talks
Katherine CliftonKatherine Clifton2 talks
Erin CobainErin Cobain2 talks
Alison ConlinAlison Conlin@aliconlinmd2 talks · chairs 1
Massimo CristofanilliMassimo Cristofanilli2 talks · chairs 2
Brian CzernieckiBrian Czerniecki@bczernieckimd2 talks
Oana DanciuOana Danciu2 talks
Ajay DhakalAjay Dhakal@dhakalajay1 talk · chairs 1
JDJames Dickerson2 talks
Fred DirbasFred Dirbas2 talks · chairs 1
Milana DolezalMilana Dolezal2 talks · chairs 1
Leif EllisenLeif Ellisen2 talks · chairs 1
Laura EssermanLaura Esserman3 talks · chairs 2
SGShridar Ganesan2 talks
GGGad Getz2 talks
Antonio GiordanoAntonio Giordano@antgiorda3 talks
KGKarthik Giridhar2 talks
Hadar GoldvaserHadar Goldvaser2 talks
Joshua GruberJoshua Gruber@joshuagruber2 talks · chairs 1
KGKalpna Gupta2 talks
Ariella HankerAriella Hanker@ariellahanker2 talks
Lynn HenryLynn Henry2 talks · chairs 1
Sara HurvitzSara Hurvitz4 talks · chairs 1
Toshi IwaseToshi Iwase2 talks
JJJordan Jackson1 talk · chairs 1
Adriana KahnAdriana Kahn@adrianakahnmd2 talksNimmi KapoorNimmi Kapoor@drnimmikapoor2 talks
HKHolly Knoderer1 talk
Henry KuererHenry Kuerer@henrykuerer2 talks · chairs 1Roberto Leon-FerreRoberto Leon-Ferre@rleonferre2 talks
MLMinetta Liu2 talks
Doris MakariDoris Makari1 talk
AMAshley Matusz-Fisher2 talks
Kelly McCannKelly McCann@drkemccann3 talks · chairs 1
RMRita Mukhtar1 talk
PMPamela Munster2 talks · chairs 1
Kelsey NatsuharaKelsey Natsuhara2 talks
Yelena NovikYelena Novik2 talks
Joyce O'ShaughnessyJoyce O'Shaughnessy@bcjoyceo3 talks · chairs 3Coral OmeneCoral Omene@omene_co2 talks
TPTanmayi Pai2 talks
TPTuya Pal2 talks
Mark PegramMark Pegram6 talks · chairs 3
EPEdith Perez1 talk
Emanuel PetricoinEmanuel Petricoin2 talks
Mary Kathryn PitnerMary Kathryn Pitner1 talk
JRJennifer Rosenbluth2 talks
Arya RoyArya Roy@royaryam2 talks
Anton SafonovAnton Safonov2 talks
Anna SchreiberAnna Schreiber@annaschreibermd2 talksMina SedrakMina Sedrak@minasedrakmd2 talks
Victoria SeewaldtVictoria Seewaldt2 talks
Elena ShagisultanovaElena Shagisultanova2 talks
Priyanka SharmaPriyanka Sharma3 talks
Rebecca ShatskyRebecca Shatsky@dr_rshatsky3 talks · chairs 1
Jenni ShengJenni Sheng2 talks
Dennis SlamonDennis Slamon3 talks · chairs 2
Corey SpeersCorey Speers@cwspeers2 talksShane SteckleinShane Stecklein@shanestecklein3 talksSandra SwainSandra Swain@sandraswainmd3 talks · chairs 1
Shou-Ching TangShou-Ching Tang2 talks
Jessica TaoJessica Tao2 talks
Christos VaklavasChristos Vaklavas4 talks
Marko VelimirovicMarko Velimirovic@marko_velimir2 talks
NVNeha Verma2 talks
Irene WapnirIrene Wapnir@wapnir2 talks
TWTomer Wasserman1 talk
YYYuan Yuan2 talks
39 named on the podium

Trials Presented

Every trial named from the podium or in the programme. The 11 in green have a full KOL Pulse trial profile — click through for the data, the KOL commentary and the regulatory status.

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9 sessions · 44 talks

Wed, Aug 19, 2026

Keynotes

Moderator · Joyce O'Shaughnessy
AM2 of 2 with slides

DAY 1: Keynotes by expert starting soon #DAVABreast

2026 Kona Breast Cancer Summit — Keynotes session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Dr. Laura Esserman and Dr. Dennis Slamon kick off the 2026 #DavaBreast #DavaOnc

2026 Kona Breast Cancer Summit — Keynotes session
VVinay Jain@VinayJaink9vh2026-08-19Source post on X ↗
Target selection in breast cancer: What have we learned?Dennis Slamon

Insightful start to #DAVABreast as Dr. Dennis Slamon of @dgsomucla reviews principles of antibody and ADC targeting in breast cancer. From HER2 to next-generation ADC targets, his talk focused on mechanisms such as ADCC and growth-signal blockade, alongside DESTINY-B01 data showing a 62% ORR and median PFS of 19.4 months.

2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?
[Slide 2] Kaplan-Meier / survival curve — table and text data only
DESTINY-B03: Primary Endpoint: PFS by BICR T-OXA aprs. no (95% (i) 12-me PFS rate, % Progression-Free Survival Probability % BREAST Censor mPFS (investigator): 25.1 mo V 7.2 mo CANCER TOM1 (n. 263) Time, months Patients Still at Risk: Median PFS follow-up fir T-Dike - 15 months (range, 15. and for CM1 - 13.9 norths pange 11.8-15.1) HR, have ration INV. investigator me, month NL not extration NK not reached Cortes A at ak Abstract Lib Presented at ESMO 2021 Amual Meeting September 16-21 2021 Cortes, Jet . ESMO 2021
[Slide 1] Claudin 6 VS. HER2 Normal tissue expression CLDN6 Gene Expression Levels in No " / % HER2 Gene Expression Levels in Normal Tissues (for comparison) Ь BREAST CANCER Ь TORL BIOTHERAPEUTICS CONFIDENTAL INFORMATION DO DISTRIBUTE --- [Slide 3] ARK2 cells stained with h23-7 and 2o anti-human-AF647, Image ID #1, Time: 0 min Time: 5 hours 35 min BREAST CANCER 2026 comes --- [Slide 4] MOAs of therapeutic antibodies in cancer Make the cancer cell more visible to the immune system through antibody-dependent cellular cytotoxicity (ADCC) i.e. rituximab Block growth signals by blocking ligand binding site on the receptor, i.e. cetuximab Block growth signals by altering receptor dimerization, i.e. trastuzumab Block growth signals by blocking ligand. Stop new REAST blood vessel formation by binding VEGF, i.e. CANCER bevacizumab 2016 - Deliver toxic drugs directly to the tumor antibody drug conjugates (ADCs)
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Opening the 2026 #DAVABreast with Dr. Dennis Slamon’s lecture on Target selection in breast cancer. HER2 checks all the boxes

2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?2026 Kona Breast Cancer Summit slide — Dennis Slamon, Target selection in breast cancer: What have we learned?
[Slide 1] 83383 88888 AOncology 2 DAVAOncology g successful drug development _facilitating successful drug development 83888 NA SUMMIT 8 8 8 8 & D 4th SUMMIT ON 88888 BREAST CANCER 8 2026 HAWAII MODERATOR 28888 DAVAOnc of 8 8 8 facilitating successful drug Oncology raful 8 n 8 D AVAOnergy DIAOndogy DAVAOncology DAVAOncology Novel mAb Targets in Breast Cancer: Lessons rom.HER2 - --- [Slide 2] What Makes an Ideal mAb or ADC Target? 1.) Malignant tissue specific expression? a.) Tumor VS normal cells b.) If normal cell expression is present, what tissues are at risk? 2.) Is the target a family member of related proteins? 3.) Is the targeted epitope shared by non-family proteins? 4.) When engaged, is the target internalized 5.) Does it traffic to the correct subcellular organelle
Antonio Giordano, MD PhDAntonio Giordano, MD PhD@antgiorda2026-08-19Source post on X ↗
I-SPY Trial: An example of multi-disciplinary drug developmentLaura Esserman

How can adaptive trials accelerate breast cancer drug development? Dr. Laura J. Esserman of @UCSF highlights I-SPY2.2 and the broader I-SPY platform, with 23 agents tested, 10 graduated and 2,118 patients enrolled. The patient-centered design uses biomarkers, RPS, MRI/biopsy and RCB endpoints to guide treatment switching and maximize RCB 0/1 while limiting unnecessary toxicity. #DAVABreast

I-SPYI-SPY2
2026 Kona Breast Cancer Summit slide — Laura Esserman, I-SPY Trial: An example of multi-disciplinary drug development2026 Kona Breast Cancer Summit slide — Laura Esserman, I-SPY Trial: An example of multi-disciplinary drug development2026 Kona Breast Cancer Summit slide — Laura Esserman, I-SPY Trial: An example of multi-disciplinary drug development2026 Kona Breast Cancer Summit slide — Laura Esserman, I-SPY Trial: An example of multi-disciplinary drug development
[Slide 1] The Platform Trial Multiple agents in parallel from different companies Each agent to be tested is a scalable and replicable process Biomarker rich -- study heterogeneity prospectively, iterative strategy Continuous improvement by design & learning system ------------------------- Master protocol to improve efficiency, speed BREAST CANCER Refine endpoints I-SPY QL - Ь - - ------------------------- I --- [Slide 2] I-SPY2.2 : Adapt treatment to individual response Sequential Multiple Assignment Randomized Trial (SMART) design Maximize the chance of reaching RCB 0/1 for each patient Key features of patient-centered design: - Evaluate new, non std chemo agents in first treatment block, using early endpoints (MRI, Bx) - Minimize toxicity (if predicted pCR surgery; if poor response-> move to next block of therapy - Block B: proven subtype-matched treatments Goal: 90% of patients to RCB 0/1 BREAST CANCER BLOCK A BLOCK B BLOCK c 2026 EXPERIMENTAL Tx BEST BY APS APS RESCUE CHEMO RO - Screen Randomize Surgery I-SPBY QL --- [Slide 3] Endocrine Optimization Protocol (EOP) Common Screen PI: Dr. Jo Chien, UCSF MammaPrint Low MammaPrint High 1 MammaPrint High HR+, HER2- HR+, HER2- All other subtypes SET High, EOP Protocol RPS HR+ Immune neg I SPY 2.2 Protocol 9 arms to date EOP or I SPY 2.2 BREAST EOP Key Eligibility Criteria EOP Key Components CANCER 22.5 cm Primary endpoint: feasibility 2026 HR+/HER2- ~20-80 participants per arm MammaPrint low risk All high risk patients can be on a trial 2025 Quantum ecp eathcore Confidential and Proprietory Allinights neserved. aserved. 76 --- [Slide 4] $ Response-Predictive Subtypes (RPS) RPS developed from ~990 HR+HER2-Immune- I-SPY2 patients across 9 experimental HR+HER2- and control arms (Wolf et al Cancer Cell) Reflects different predicted sensitivity to HR-HER2-Immune- Immune, DNA damage repair deficiency, and HER2-targeting agents HR-HER2 HR+HER2-Immune+ Simplified to focus on predicted 10 and - BREAST anti-HER2 therapy sensitivity CANCER HR-HER2-Immune* Used to inform I-SPY 2 Block B agent HR+HER2+ S5:HER2+HER2orBasal drug assignments/randomization HR-HER2+ S6:HER2+Luminal Perform better than receptor subtypes
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Selective Estrogen Receptor Degrader/Modulator

Moderator · Mark Pegram
AM6 of 8 with slides

Coming up Next: Selective Estrogen Receptor Degrader/Modulator, Moderated by Dr. Mark Pegram #DAVABreast

2026 Kona Breast Cancer Summit — Selective Estrogen Receptor Degrader/Modulator session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Takeaways from the SERENA-6 trial of camizestrant + CDK4/6 inhibitorMassimo Cristofanilli

Can ctDNA catch resistance before it shows on scans? SERENA-6 used ctDNA to detect emergent ESR1m in 1L HR+/HER2- MBC, switching to camizestrant + CDK4/6i. Updated median PFS 16.8 vs 9.2 mo (HR 0.45); PFS2 25.7 vs 19.1 mo. Massimo Cristofanilli, @WeillCornell #DAVABreast

SERENA-6profile
2026 Kona Breast Cancer Summit slide — Massimo Cristofanilli, Takeaways from the SERENA-6 trial of camizestrant + CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Massimo Cristofanilli, Takeaways from the SERENA-6 trial of camizestrant + CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Massimo Cristofanilli, Takeaways from the SERENA-6 trial of camizestrant + CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Massimo Cristofanilli, Takeaways from the SERENA-6 trial of camizestrant + CDK4/6 inhibitor
[Slide 1] SERENA-6: Summary . Start of 1L therapy First PD Second PD Randomisation (accessed by RECIST) accessed by RECIST) (MA Time from rendomisation - TMA Time from rendomisation no second Emergence of disease progression, or death from any objective doesse progression, or death from treatment levse, whichever occurs, from any cause, whichever me resistance Patients on 1L treatment with Al CDK4/6i Al CDK4/6i Continue Al CDK4/6i 2L 3L emergence . 26 mo during 11. without PD -40% patients develop an ESRIm by end of 11' Ongoing (5R1m CEDNA Monitoring SERENA-6 2L 3L in-line witch to camizestrant . continue CORA/SI BREAST CANCER PFS 2026 First PD Second PD HAWAII (accessed by RECIST) (accessed by RECIST) PFS2 Weill Cornell Medicine - - - for addression and references. 100 --- [Slide 2] SERENA-6 study design Phase III, randomized, double-blind, placebo-controlled study (NCT04964934) Camizestrant (75 mg qd) + continuing CDK4/6i Primary endpoint Female/male patients with ER+/HER2-ABC* + placebo for Al PFS by investigator Stratification factors assessment (RECIST v1.1) All patients that have received AI + CDK4/6i Visceral vs non-visceral Secondary endpoints (palbociclib, ribociclib, or ESRfm detection at first test vs at a abemaciclib) as initial R11 subsequent test PFS2** endocrine-based therapy for N=315 Time from initiation of AI * CDK4/6 to ABC for at least 6 months randomization: <18 vs >18 months OS** Palbocidlib vs ribociclib vs abemaciclib BREAST ESR1m detected in ctDNA Safety CANCER with no evidence of disease Continuing AI (anastrozole/ progression letrozole) + CDK4/6i Patient-reported + placebo for camizestrant outcomes Treatment continued until disease progression, unacceptable toxicity, patient withdrawal or death - or permenopas worther, and men received usensing name remaining normone agonest per clinical guidelles "Key secondary endport ce - PFS2, progression-the survive at once Saily lose, R andomized REGIST, response evaluation Vileria in solid uners Weill Cornell Medicine 97 --- [Slide 3] SERENA-6 screening step: patient disposition Patients could enter SERENA-6 at any point during The median time on Al CDK46i at the time of , first-line AI CDK4/6 treatment as long as they had entry into the SERENA-6 screening step was 0000000 received at least 6 months of treatment 14.9 months (IQR: 9-27) Time on first-line Al CDK4/6i I Patients with HR+/HER2-ABC For those not positive for ESR1m at first test, continued testing coincided with routine clinical assessments (every 2-3 months) Switch to camizestrant + Patients who received Patients no longer in 10.00 continued CDK4/6i BREAST 0000000000 21 ESRfm test, ESRIm surveillance when n=3256 screening closed, " 1307 Patients with an Randomised CANCER ESR1m, n=548 patients, n=315 Continue Al CDK4/6i 2026 names ESR1m screening closed when the target number of randomised patients Patients with ESR1m and was reached At this time, 1949 patients were ongoing ESR1m surveillance concurrent disease progression, (no ESR1m detected and no disease progression) n=117/548 (21%) The crude estimated ESRim detection - in SERENA4 - 42% deculated as 548 patients with positive (he number if patents inted for ESRtm (n=3256) mas the number If patients that were ($) organing - surveilance when screening dosed (n-1949). Weill Cornell Medicine to 92 --- [Slide 4] Takeaway messages Feasibility of using ctDNA monitoring to detect ESR1m in endocrine sensitive HR+ MBC Demonstrated the impact of a new treatment strategy: Intercept of molecular progression improves disease control and delays clinical progression and chemotherapy use Continuation of CDK4/6 inhibitor and introduction of SERD BREAST CANCER Improved QoL 2026 Molecular response endpoint validate clinical results HAWAII Weill Cornell Medicine 90
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Therapeutic rationale for imlunestrant with abemaciclib or other agentsKelly McCann
Update on elacestrant trialsMark Pegram

How is elacestrant evolving beyond monotherapy? Dr. Mark Pegram reviews ELEVATE combinations in ER+/HER2- breast cancer. Elacestrant + capivasertib achieved 33.3% ORR, 66.7% CBR24 and 88.9% DCR; median PFS was 10.9 months in ESR1/PIK3CA co-mutated disease. #DAVABreast

ELEVATE
2026 Kona Breast Cancer Summit slide — Mark Pegram, Update on elacestrant trials2026 Kona Breast Cancer Summit slide — Mark Pegram, Update on elacestrant trials2026 Kona Breast Cancer Summit slide — Mark Pegram, Update on elacestrant trials2026 Kona Breast Cancer Summit slide — Mark Pegram, Update on elacestrant trials
[Slide 2] Kaplan-Meier / survival curve — table and text data only
ELEVATE (Elacestrant + Abemaciclib): Progression Free Survival Ela + Abema Elacestrant . abemaciclib 2 Events, Subgroup mPVS, mo(95% Cl 14.3(7.3-16.6) mPFS. months (95% CI) All patients Visceral disease No prior fulvestrant No primary endocrine resistance - - time nadas (PTN ce - Overal - - --- reasize Maturity not reached for PFS (95% Ct) for genomic subgroups (ESR1/PIKICA) BREAST or by prior COKAN exposure CANCER Ela . Abema showed 91.2% DCR, 24.6% ORR, 14.75 mos mDOR Months N Rsk - Elacestrant + abemaciclib showed a consistent PFS benefit across key subgroups Key clinical characteristics Visceral metastases 92% primary ET resistance 15% ESRIM 33% (1023) PIK3CAM 27% Prior COKAIBI 50% Prior Investment 30% REGIONAL COLLOQUIA ON ER+/HER2- BREAST CANCER Plope Ruge, SABCS 2125
[Slide 3] Kaplan-Meier / survival curve — table and text data only
ELEVATE (Elacestrant + Abemaciclib): Progression Free Survival Ela + Abema Elacestrant * abemaciclib Events (%) APFS no(95% a 14.3(7.3-16.6) Subgroup mPFS, months (95% CI) All patients Visceral disease No prior fulvestrant No primary endocrine resistance - - TYPE - 99% 08 notes Drew " 03/20 ARC AND CAMER Maturity not reached for PFS (95% 00 for genomic subgroups (ESRT/PIKICA) BREAST or by prior COKE exposure CANCER Ela . Abema showed 91.2% DCR, 24.6% ORR, 14.75 mos mDOR Months Elacestrant + abemaciclib showed a consistent PFS benefit across key subgroups Key clinical characteristics Visceral metastases 92% primary ET resistance 15% ESRIN 33% (10/23) PIK3CAm 27% Prior COKA 50%, Prior fulvestrant 30% REGIONAL COLLOQUIA ON ER+HER2- BREAST CANCER Hope Ruge SABCS 2025 & DAVA/Oneology
[Slide 1] ELEVATE (Elacestrant + Capivasertib): Overall Response Rate All objective responses occurred in patients whose Elacestrant 345 mg + 90% tumors harbored both ESRTand PIK3CA mutations net Capirasertib 320 mg 50% - % 40% BOR' I Change From 20% - - - - Complete Response 0 0 - PROCER PTENE PROCAR PROCAR 0% Partial Response 3 33.3 States Disease $ 55.6 20% $ $ : I Progressive Disease 11.1 I ORR (95% C0 30.3% (7.5-70.1) I DCR 00.0 I - CBR 24 weeks 66.7 I mDOR, months (95% CI) NR (7.4-NR) 100% BPR #SD RPD - BREAST CANCER Elacestrant 345 mg + capivasertib 320 mg 1 showed 88.9% DCR, 66.7% CBR24, 33.3% ORR, - mDOR has not been reached . . - : - - REGIONAL COLLOQUIA ON ER+/HER2- BREAST CANCER Wassim McHayleh, ASCO 2026 R DAWA/Onoology --- [Slide 4] Phase 3 EMERALD Clinical Trial: Study Design - Deceasivent - Fulvestrent PFS Months - - - withdrawal A ! R - RS 1:31 E I MK) - - - - : BREAST CANCER Key baseline patient and characteristics balanced: nensa Visceral Metastasis 70% Prior Adjuvant Therapy -55-65% Prior Al ->80% Bdard FC. et ak a /Cle Oncol 2022:4028)3246-3256 Prior Fulvestrant -25-30%
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Giredestrant in ER+, HER2- BC: 1st and 2nd line MBCChristos Vaklavas

Journey of Endocrine targeted therapies: Dr. Christos Vaklavas @huntsmancancer discusses the role of giredestrant in HR+/HER2- mBC? He reviews ESR1 biology and persevERA, where median PFS was 33.1 vs 28.2 months with giredestrant + palbociclib vs letrozole + palbociclib (HR 0.89; p=.1553), not meeting significance. #DAVABreast

2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Giredestrant in ER+, HER2- BC: 1st and 2nd line MBC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Giredestrant in ER+, HER2- BC: 1st and 2nd line MBC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Giredestrant in ER+, HER2- BC: 1st and 2nd line MBC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Giredestrant in ER+, HER2- BC: 1st and 2nd line MBC
[Slide 1] mESR1: Clinical Implications SERDs in combination with targeted therapies (evERA trial) 2347 wallinge Entroges/independent relation Entrogen dependent DA dependent Entrages independent - TO - - Migration - Morility Canamical sites Metastasis Noncanenical - I Created in I Ь ## BREAST - CANCER . - . - . line - II : : : : 7 1 1 Combination with ------------------------- - to correctly meaningful I NA - of - - patients with ESMITAL Marth M. at X Giredestrant for Estrogen Receptor-Positive, HER2 Negative Previously Treated Advanced Breast Cancer Results From the Randomized, Phase a KHERA Breast Cancer Study. 200 2024 ax Mayer B. eral. Giredestrant (GRE), an oral selective cestrogen receptor (ER) antagonies and degrader, . everolimes #) - patients (pts) with R-positive, HER2-negative advanced breast cancer ER+, HER2- abC) previously treated with , CDKA/6 inhibitor II: Primary results or the Phase " IVERA BC trial. ESMO 2025 2025. --- [Slide 2] Precedence of SERDs in 1L HR+/Her2- MBC FALCON & PARSIFAL Clinical Trials Fulvestrant Fulvestrant, 16. months Anastrozole, 13.8 months N 230 R Anastrozole N 232 Fulvestrant palbociclib 27.9 Fulvestrant + months Letrozole . 32.8 months BREAST palbociclib CANCER R N - 243 Letrozole + palbociclib N=243 Robertson JFR of a Fulvestrant 500 mg versus anastroable 1 mg for hormone reception positive advanced breast cancer (FALCON) as international randomised double blind, phase Hal. Lancel 2016 Dec 3005 ax 10. 1016/50145 6736(16)32389-3 Robertson JFR of at Fulvestrant Versus Anastrozole in Endocrine Therapy Naive Women with Mormone Receptor Positive Advanced Breast Cancer Final Overall Survival in the Phase " FALCON Trial. JCO 2025 May:43(13) 1539-1545 doc A, et as Extended follow-up of with fulvestrant or introzole for endocrine- sensitive, hormone receptor positive HER2 negative advanced breast cancer in the PARSIFAL trial ESMO Open 2025 Jul 10(7) 105309 doc 10 1016) esmoop 2025 105309. --- [Slide 3] persevERA: giredestrant in 1L HR+/Her2- MBC The Moment of Truth Primary endpoint: INV-PFS Giredestrant Letrozole palbociclib palbocialib n 495 n= 497 100 90 Events n(%) (%) 300(60.6) 323(65.0) " 77.8% 77.3% Median months 33.1 28.2 N (95% CI) (30.2,38.3) (25.0,33.1) 99.7% " Stratified HR 0.89 57.3% $ 41.8% " (95% CI) 40 41.9% Median follow-up N Gredestrant am 52.2 months Fange 0.4-63.5) BREAST - morths Panger 03-42-0 N CANCER 2 - - I . 2 - 0 0 TO 12 14 14 10 Time --- - - - - : - furner NC, - . understand GRE persiciants PALICE - Insurance (LEX) PALBO - - (14) meney - paterial une with estragen receptor positive, REFU- regative locally achanced or metains: trant --- ER. HERO- LAMBO minery mayes or - Provider - 60 - ASDO HAIL 149 --- [Slide 4] persevERA: giredestrant in 1L HR+/Her2- MBC Study Schema Key eligibility criteria: 1L CR-, HDO- LAWDC' Giredestrant 30 mg PO QD Locally confirmed histologic/cytologic . placebo PO QD diagnosis N-992 palbocialib 125 mg PO go Day 1-21 No prior treatment for advanced doease on each 26-day cycle Treatment until PO or SURVIVAL No prior treatment with a SERO 11 unacceptable FOLLOW-UP Deasse recurrence . 12 months from completing prior (necludiuvant tamoxifes/Al Latrazole 2.5 mg PO 00 toxicity placebo PO go Disease recurrence $ 12 months for patients pelbocialib 125 mg PO 00 Day 1-21 receiving tamexter protocol vit) on each 25-day cycle No active cardiac disease or history of cardiec dysfunction BREAST Patients with de nove mBC were capped at 20% CANCER Stratification factors Primary the of Issue Viscers - non visceral 2026 Investigator assessed PFS BNY PFR - RECIST vi.1 Menopousel status Post menopausal in pre menopausal/male Region North America vs Western Curope - - Pacific is other 06, ORR, CBR DoRt safety, PROs (TTD of pan, physical functioning TFI since the and of prior (rec)edjuvant therapy De novo role functioning GHS/QeL) meterials in . 12 months vs . 12 months Turner NO Gendestrant DIFE patecide - - am - - - therapy " patients - with estrogen receptor positive HERJ regative locally advanced - materials breast cancer ER- HERO- LAWBO Primary analysis of the Phase no 147
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Vepdegestrant, an ER PROTAC, for ESR1-mutant breast cancerKelly McCann

Can PROTAC-mediated ER degradation improve outcomes after CDK4/6i? Dr. @DrKEMcCann of @UCSanDiego reviews VERITAC-2: in ESR1-mutated ER+/HER2- advanced breast cancer, vepdegestrant improved median PFS to 5.0 vs 2.1 months with fulvestrant (HR 0.57; p<.001). Grade ≥3 AEs were 23.4% vs 17.6%, with dose reductions or discontinuations remaining uncommon. #DAVABreast

2026 Kona Breast Cancer Summit slide — Kelly McCann, Vepdegestrant, an ER PROTAC, for ESR1-mutant breast cancer2026 Kona Breast Cancer Summit slide — Kelly McCann, Vepdegestrant, an ER PROTAC, for ESR1-mutant breast cancer2026 Kona Breast Cancer Summit slide — Kelly McCann, Vepdegestrant, an ER PROTAC, for ESR1-mutant breast cancer2026 Kona Breast Cancer Summit slide — Kelly McCann, Vepdegestrant, an ER PROTAC, for ESR1-mutant breast cancer
[Slide 2] Kaplan-Meier / survival curve — table and text data only
VERITAC-2: PFS by BICR in Patients With ESR1m Vepdegestrant Fulvestrant - Vepdegestrant — Fulvestrant Median follow-up, months Events, n (%) Median PFS, months 6-month PFS (95% CI): PFS (%) Stratified HR (95% CI) 2-sided P<0.001 BREAST CANCER HAWAII No. at risk Time (Months) Vepdegestrant Fulvestrant - © Copynght - Hamilton (if et at Clin Oncol 13, 2025 (suppl 17, ability (BA1000) Presented by trike Hamiton, MO, - ASCO 2025 Used and adapted with permission
[Slide 1] Mechanism of proteolysis-targeting chimera (PROTAC) Ub Ub E3 ligase Ub Ubiquitin- proteasome 13 ligase Ub system (UPS) recruiter Linker Protein of PROTACs don't have to be small interest molecules, but small molecules are useful Warhead BREAST CANCER drugs because they cross the plasma membrane. Does not have to bind to a 2026 HAWAI ligand site to achieve Fun fact: Some viruses make their own PROTACs. For protein degradation example, HPV16's E6 protein is a PROTAC that recruits E3 ligase to ubiquitinate p53. ACS Med. Chem Left 12(7): 1056-1060 (2021). 159 abmole com/products/arv 471 html --- [Slide 3] VERITAC-2: Safety and Tolerability (All Treated Patients) Overview TEAEs in >10% of Patients in Either Group Vepdegestrant Fulvestrant Vepdegestrant Fulvestrant TEALS, % (n=312) (n=307) n= 312) (a= 307) Any grade 87 81 TEAL, % Any Grade Grade 3/4 Any Grade Grade 3/4 Grade 23 23 18 Fatigue* 27 1 16 1 Serious 10 9 ALT increased 14 1 10 1 Leading to treatment discontinuation 3 1 AST increased 14 1 10 $ Leading to dose reduction 2 NA TRAEs, % Nausea 13 0 9 1 Any grade 57 40 Anemia 12 2 8 3 BREAST Grade 23 8 3 Neutropenia 12 2' 5 1" CANCER QT prolongation Back pain 11 1 7 <1 2026 TEAEs vepdegestrant, 10% fulvestrant, 1% HAWAI A QT interval sub study (n=88) confirmed a mild increase (11. 1 ms) from Arthralgia 11 1 11 0 baseline in mean QT:F, with upper 90% CI (13.7 ms) <20 ms,' indicating no large QT-prolonging effect Decreased appetite 11 <1 5 0 - - - - - - of - - - retrod - energen adverse - TRAE - - - - - - - - - - - - X - - - - - - - - - - - - - - - and - - - - ------------------------- I , I I I / I I I I I I I il I I 2 I I . 2 I I I I I I I 1 I . 1 Hamilton " - - - - 13, 2025 (suppl 17; HAVY BASDOD) Presented by THE Hamiton, MD, in ASCO 2025 Used with - --- [Slide 4] VERITAC-2: Global Phase 3 Trial of Vepdegestrant Key Eligibility Criteria 28-day Treatment Cycles Age >18 years old Primary Endpoints: ER+/HER2- advanced or metastatic breast Vepdegestrant (n=313) PFS by BICR in cancer Prior therapy: 200 mg orally (once daily) - ESR1m population - 1 line of CDK4/6 ET - <1 additional ET Randomization (1:1) - All patients Secondary Endpoints: - Most recent ET for 26 months - No prior SERD leg. fulvestrant, Fulvestrant (n=311) os (key secondary) elacestrant) 500 mg IM CBR and ORR by BICR - - No prior chemotherapy for advanced (days 1 and 15 of cycle 1; day 1 of BREAST or metastatic disease subsequent cycles) AEs CANCER Radiological progression during or after Stratification Factors: 2026 the last line of therapy HAWAII ESRI mutation (yes vs no) Visceral disease yes vs no) Data cutoff date Jan 31,2025 - - - - ONLY Foundaine Medicare - Own - Origned ling - - Clinicatrials gov: NCT05654623 - rependent - - level - dependent - LA - waper - recepter - was pre - Trensforme Pay epairmal - - response - - - - - - - legister Hamilton EP et at Can Oncel 43, 2025 (suppl 17; ability (8A5000) Presented by crea Hamilton, MO, - ASCO 2025 Used with permission
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Ongoing trials with palazestrant in newly diagnosed ER+ MBCElena Shagisultanova

Dr. Elena Shagisultanova of @JeffersonUniv reviews palazestrant, a CNS-penetrant complete ER antagonist and degrader active against wild-type and mutant ER. Early ribociclib combinations showed tolerable safety and no DDIs, with ph III OPERA-02 evaluating 90 mg palazestrant + ribociclib vs letrozole + ribociclib in 1L ER+/HER2- ABC. #DAVABreast

2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Ongoing trials with palazestrant in newly diagnosed ER+ MBC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Ongoing trials with palazestrant in newly diagnosed ER+ MBC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Ongoing trials with palazestrant in newly diagnosed ER+ MBC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Ongoing trials with palazestrant in newly diagnosed ER+ MBC
[Slide 2] Kaplan-Meier / survival curve — table and text data only
Activity observed in overall population and prior CDK4/6i subgroup PFS in all patients and in patients with prior CDK4/6 inhibitor treatment Programision I 2 I . Median PTS. - Median PTS. - - PFS BREAST Time (months) Tabe (nonths) CANCER Number Nueral - Poder - / (SMO Congress 20% Order Certery Poster NOP In the 120 mg palazestrant dose cohort, the median PFS was 15.5 months for all patients and 12.2 months for patients with prior CDK 4/6i-treated ABC. In the 90 mg palazestrant dose cohort, the median PFS was not reached at a follow up time of 10.8 months.
[Slide 1] Endocrine resistance remains a challenge in ER+, HER2- advanced breast cancer (ABC) Standard 1L treatment for ER+, HER2-ABC is an aromatase inhibitor plus CDK4/6 inhibitor. CDK4/61 Trial in 1L ABC PFS vs placebo HR (p) os vs placebo HR (p) palbociclib PALOMA-2 24.8 vs 14.5 0.58 (p<0.001) 53.9 vs 51.2 0.96 (p=0.34) ribociclib MONALEESA-2 25.3 vs 16.0 0.57 (p<0.001) 63.9 vs 51.4 0.76 (p=0.008) abemacidib MONARCH-3 28.1 vs 14.8 0.54 (p<0.001) 66.8 vs 53.7 0.80 (p=0.066) Despite these advances, patients ultimately develop resistance to Al . CDK4/6i therapy A key mechanism of endocrine resistance involves activating mutations BREAST in the ESR1 gene encoding ERa CANCER Mutations occur in the ligand-binding domain (AF2) 2026 - They lead to estrogen-independent constitutive activation of ERa Therapeutic approaches that inhibit both wildtype and mutant ERa in I 1L ABC may help maintain endocrine sensitivity, delay resistance, and 1 improve long-term clinical outcomes. --- [Slide 3] Early Phase Study of Palazestrant in Combination With Ribociclib: OP-1250-003 (NCT05508906) Treatment Related AEs reported in >25% of patients Eligibility: ER-/HER2- ABC with <2 lines or prior ET+)- COK46 - - MONALESSA-P Related TEACH reported and s1 prior lines of chemetherapy for ABC - patients 20mg 1 - I - (N=334) - Grade Grade All Grade Crade All Grade Grade Study population: grades 1 . grades 3 I grades 3 4 72 patents word treated ath other 120 mg or 90 or : $ 13 1 1 7. NO - (9%) and ses) yes) IV 45% 11% mg QD polazestrant at received 600 mg ribecide 1 - Most patients (83%) were postmenopausal women (77%) ( 9 any - 0 12% 2% $ 00 . Prior lines of therapy for ABC I , I (10%) , 0 / TP% 2% ! 63% had prior CDK4/6 - . we - 10% 6 . - (18%) (WM) (25%) 0 IV 31% in 44% had prior AJ 34 , 32% had fulvestrant ( 2% I 0 - 35% 1% on 1 - 15% had prior chemotherapy - , (PM) , 0 - ( 17% 2% $ 22% of at patients had ESRI mutations 21 Formiting - : , - 0 0 29% : on $ I , , 0 - - - Safety: provinged I I 29% PM - - BREAST . The most common reason for treatment Lymphosite - - (5%) (0%) - I 0 me 12% : . CANCER discontinuation was disease progression AST - - - 9 - I 0 MV : 1% No DLTs were observed the MTD was not reached # I I , I 0 2026 Most dose reductions were done for neutropenia any - 2% 1% on No DDI between palazestrant and ribociclib - - as Power - COMO Congress - Deber an less Terminy Poster - The safety profile of palazestrant in combination with ribociclib was consistent with the known safety profile for ribociclib plus endocrine therapy I - --- [Slide 4] OPERA-02: 1L phase 3 trial in combination with ribociclib (NCT07085767) Phase 3 randomized, double blind of palazestrant with ribociclib vs letrozole with ribociclib for ER+, HER2-ABC patients who have not received prior therapy for advanced disease 90 mg palazestrant Key eligibility criteria: + 600 mg ribociclib ER*, HER2- ABC Treatment + letrozole-matching placebo* Any menopausal status until disease Evaluable disease (measurable or 1:5 progression non-measurable) N 1,000 No prior systemic therapy for ABC 2.5 mg letrozole + ribociclib or intolerable No disease recurrence during or within + palazestrant-matching toxicity 12 months of completing adjuvant therapy placebo Stratification Factors: Post-menopausal females vs pre-(peri-menopausal females and males Study Endpoints: BREAST Visceral metastasis yes " no Primary: PFS (Investigator) CANCER De nevo metastatic disease F2 recurrent blease after adjuvant ET Secondary: os (Key), PFS (BIRC) ORR/CBR/DOR Geographic region (BIRC, Investigator): Safety: PK; Health-related PROs
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ELAINE-3: lasofoxifene + abemaciclib vs fulvestrant + abemaciclibJessica Tao

Can ELAINE-3 build on earlier lasofoxifene data? Dr.Jessica Tao of @HopkinsMedicine reviews ELAINE-1, where lasofoxifene showed antitumor activity vs fulvestrant, & ELAINE-2, where lasofoxifene + abemaciclib achieved mPFS of 55.7 weeks with acceptable tolerability. Ph III ELAINE-3 now compares lasofoxifene + abemaciclib vs fulvestrant + abemaciclib after CDK4/6i progression. #DAVABreast

ELAINE-3ELAINE-1ELAINE-2
2026 Kona Breast Cancer Summit slide — Jessica Tao, ELAINE-3: lasofoxifene + abemaciclib vs fulvestrant + abemaciclib2026 Kona Breast Cancer Summit slide — Jessica Tao, ELAINE-3: lasofoxifene + abemaciclib vs fulvestrant + abemaciclib2026 Kona Breast Cancer Summit slide — Jessica Tao, ELAINE-3: lasofoxifene + abemaciclib vs fulvestrant + abemaciclib2026 Kona Breast Cancer Summit slide — Jessica Tao, ELAINE-3: lasofoxifene + abemaciclib vs fulvestrant + abemaciclib
[Slide 2] Kaplan-Meier / survival curve — table and text data only
ELAINE-1: Results JOHNS HOPKINS MEDICINE Median PFS Progression-Free Survival (PFS) LAS: 6.04 mos (2.82-8.04) — Lasofoxifene — Fulvestrant Fulv: 4.04 mos (2.93-6.04) PFS at and 12 months Survival Probability BREAST CANCER FUN LAS 12 months Months #LAS congress Crosses indicate cersoned subjects 1 month . 4 weeks Fulv, revestment LAS, PFS, progression free survival
[Slide 1] Censored Median Progression Free Survival: 55.7 weeks: JOHNS HOPKINS ........ Over Double the PFS of other CDK4/6i combinations post-CDK4/6i 1.0 I Maximum Tumer Response ELAINEZ - - - - 0.7 I I - - as " : 0.3 - Median PFS 55.7 works (13 months) (95% CL - 32 D-NE) I I I I I I 1 I . - - - BREAST . . . 1 : - 12 - - ORR: 56% (95% CL CANCER I 29.0-71.0) Median TTR: 169 days 27 - a : - I I 1 Median DoR: 252 days ORR: 56% 10/18 patients with measurable lesions had confirmed partial responses --- [Slide 3] ELAINE-3 JOHNS HOPKINS & PH3 REGISTRATIONAL TRIAL TO ESTABLISH IMPROVED EFFICACY OF LASOFOXIFENE . ABEMACICLIB COMPARED TO CURRENT SOC COMBINATION Screening (70 and Open Lebol treatment Period no " me) Study Outcomes inj - Primary Endpoint key - Citera Impossion - - **** by BOX - Key Secondary Endpoints . THE . registrar I Secondary Endpoints : E I : Cinical tenet of - . N-ME see BREAST CANCER 2026 I and CLAINS - 5 | - driven - - - - - - 197 Address for Soriz / - Fature Desision - --- [Slide 4] ELAINE-2¹ JOHNS HOPKINS ........ Open-label, phase 2, multicenter, single-arm trial to evaluate the safety and efficacy of LAS combined with Abema in post-CDK4/6i setting Women >18 years with ER+/HER2- mBC with ESR1 mutation(s) identified in circulating tumor DNA (ctDNA) Progressed on one or two lines of ET for mBC (prior Abema allowed) Up to one line of chemotherapy Patients took oral LAS 5 mg/day and Abema 150 mg twice a day (BID) until progression, death, toxicity, or withdrawal Endpoints BREAST Primary Safety and tolerability as assessed by CTCAE (V.5) CANCER Secondary Progression-free survival (PFS) Clinical benefit rate (CBR) Objective response rate (ORR) Duration of response (DoR) Time to response (TTR) 1. Demodaran 5. ASCO 2022 192
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Meta-analysis: improved OS with SERDs vs standard endocrine therapy in MBCHadar Goldvaser

Targeting mTOR/PI3 Kinase/AKT

Moderator · Adam Brufsky
AM6 of 7 with slides
Updated data and ongoing trials with capivasertibMark Pegram

Dr. Mark Pegram reviews evolving capivasertib strategies in HR+/HER2- MBC. In ELEVATE, capivasertib + elacestrant showed ORR 33.3%, CBR ~67% and DCR ~89%, with no new safety signals or PK interaction, supporting an all-oral approach. #DAVABreast

ELEVATE
2026 Kona Breast Cancer Summit slide — Mark Pegram, Updated data and ongoing trials with capivasertib2026 Kona Breast Cancer Summit slide — Mark Pegram, Updated data and ongoing trials with capivasertib2026 Kona Breast Cancer Summit slide — Mark Pegram, Updated data and ongoing trials with capivasertib2026 Kona Breast Cancer Summit slide — Mark Pegram, Updated data and ongoing trials with capivasertib
[Slide 1] Capitello-291: Efficacy Analysis . N Exploratory analysis of PFS in patients by alteration type (Global population) PIRICA starations enly AKTY sheratone any PTEN atterations any - BREAST CANCER 2028 - PERSON Turner et al, NEIM Il 2023, 388(22):2058- 2070. --- [Slide 2] Capivasertib + Elacestrant: Update from ELEVATE - - ASCO, 2026 Best Overall Response at RP2D Elacestrant 345 mg - capivasertb 320 mg: evaluable patients n-9 median follow-up 11.3 months (1.8-15.0) 7. 33.3% 88.9% 66.7% NR Objective response Disease control Cinical benefit Median DoR months (95% CI 7.5-70.1] rate (DCR) rate at 24 WKS 7.4-NR) BEST OVERALL RESPONSE (RECIST v1.1) % CHANGE FROM BASELINE (per patient) E 8 P Complete response 0 0% - - - - - - I BREAST Partial response 3 33.3% PROCAR I PRICAR I PROCAR PROCESS PRICAR 0 CANCER I - 12% $ - 2024 - $ COWER Stable disease 5 55.6% - : 45% Progressive disease 1 11.1% I Median duration of response not yet reached Wassim McHayleh, et al. Journal of Clinical Oncology. 2026;44(suppl 16):Abstract 1098. --- [Slide 3] Mutations in the PI3 Kinase/AKT Pathway are Actionable: CAPItello-291 Phase 3 Trial of Capivasertib + Fulvestrant in Al-Resistant HR+/HER2-MBC Key Eligibility Criteria PFS by Investigator in the AKT Pathway-Altered Population Recurrence while on or <12 months from end of adjuvant Al, or progression while on prior AJ for ABC 109 N 12 lines of prior endocrine therapy for ABC 90 I e I as 51 line of chemotherapy for ABC 70 Prior CDK4/6 allowed (at least 51% required) 00 50 40 30 Capivasertib * Fulvestrant - 355) 20 Capivasertib 400 mg bid* Fulvestrant 500 mg q4w 2 5 $ 18 19 20 21 22:23:24:25:26 R 1:1 Time Placebo + Fulvestrant (n-353) N-708 Placebo bid" BREAST Fulvestrant 500 mg q4w CANCER AKT Pathway-Altered Population C+F (n=155) P+F (n=134) PFS events 121 115 2026 - Dual primary endpoints: PFS by investigator in overall Median PFS, mo (95% CI) 7.3 (5.5-9.0) 3.1 (2.0-3.7) and in AKT pathway altered tumors Adjusted HR (95% CI) 0.50 (0.38-0.65) Secondary endpoints: os, ORR Two-sided P value <0.001 Stratification Factors: Liver mets, prior CDK4/6L region - days of, a - on - 1. - 14. - - - PFS benefit was observed in all key subgroups, as sustiting AKTI, PTEM sheretion including prior use of CDK4/6i and liver metastases pap cogetive furner NC SAICS --- [Slide 4] Ongoing Clinical Trials With Capivasertib (CT.gov) NCT04862663: Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPitello-292) 7. NCT07281833: Phase III Study to Evaluate the Safety, Efficacy, and Impact on Quality of Life of Capivasertib Alongside Standard-of-care Endocrine Treatment in Patients With HR+/HER2- Advanced Breast Cancer and Progression on Prior Endocrine-based Treatment (CAPIcorn) NCT06607757: Capivasertib Plus Fulvestrant vs. Fulvestrant in Primary High-risk Lobular Breast Cancer NCT07426822: Rash & Diarrhea Prophylaxis With Capivasertib NCT05455619: Evexomostat (xanthine oxidase inhibitor) Plus PI3K or AKT Inhibitor and Fulvestrant in Patients BREAST CANCER With a PI3K Alteration and HR+/Her2- Breast Cancer NCT05720260: Immunotherapy, Hormone Therapy, and AKT Inhibitor for Premenopausal ER Positive MBC NCT07343960: A Phase I Study to Investigate the Pharmacokinetics and Safety of Capivasertib in Participants With Moderate Hepatic Impairment NCT06927648: Capivasertib Regulatory Postmarketing Surveillance In Korea
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Ongoing trials with inavolisib in PIK3CA-mutant metastatic breast cancerSandra Swain

Targeting PIK3CA in the first line: Dr. Sandra Swain of @gumedcenter provides an overview of the INAVO program, highlighting INAVO120, where inavolisib + palbociclib + fulvestrant improved median PFS to 17.2 vs 7.3 mo and OS to 34.0 vs 27.0 mo, alongside ongoing INAVO121/122 studies. #DAVABreast

2026 Kona Breast Cancer Summit slide — Sandra Swain, Ongoing trials with inavolisib in PIK3CA-mutant metastatic breast cancer2026 Kona Breast Cancer Summit slide — Sandra Swain, Ongoing trials with inavolisib in PIK3CA-mutant metastatic breast cancer2026 Kona Breast Cancer Summit slide — Sandra Swain, Ongoing trials with inavolisib in PIK3CA-mutant metastatic breast cancer2026 Kona Breast Cancer Summit slide — Sandra Swain, Ongoing trials with inavolisib in PIK3CA-mutant metastatic breast cancer
[Slide 3] Kaplan-Meier / survival curve — table and text data only
INAVO120: Updated PFS Events, n (%) Median, Mo (95% CI) Inavolisib (n = 161) Placebo (n = 164) Hazard ratio: 0.42 (95% Cl: 0.32-0.55) Median follow-up: 34.2 mo PFS (%) Inavolisib BREAST CANCER Placebo Patients at Risk, n Inavolisib Placebo 164 125 95 74 50 34 30 24 21 14 11 10 8 4 2 1 1 1 furner. ASCO 2025. Abstr 1003. thaveri NEJM. 2025;(fpub). Slide credit clinicaloptions.com CCO
[Slide 1] INAVO120: Study Design . 0 International, double-blind, randomized phase III trial Stratified by visceral disease (yes vs no), endocrine resistance (primary vs secondary), region (North America/Western Europe vs Asia vs other) : Inavolisib 9 mg PO QD + Adults with PiK3CA-mutated, HR+/HER2- advanced breast cancer confirmed with Palbociclib 125 mg PO QD D1-21 + central or local ctDNA or local tissue; Fulvestrant 500 mg C1D1/D15 and Q4W measurable disease per RECIST v1.1; (n 161) Until PD or PD during/within 12 mo of completing adjuvant ET; no prior therapy for advanced toxicity Placebo PO QD + BREAST breast cancer; fasting glucose <126 mg/dL Palbociclib 125 mg PO QD D1-21 + CANCER and A1C <6.0%; ECOG PS 0/1 (N 325) Fulvestrant 500 mg C1D1/D15 and Q4W (n 164) Primary endpoint: PFS by INV Enrollment: January 2020 to September 2023 Data cutoff: November 15, 2024 Key secondary endpoints: OS; ORR, BOR, CBR, and DoR by INV; PROs Turner ASCO 2025 Abstr 1003 thavers NEJM. 2025;|Epub]. Side credit clinicaloptions.com CCO --- [Slide 2] INAVO121: Phase 3 Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant in HR+, HER2-, PIK3CA-mut Locally Advanced/mBC post CDK 4/6i Inavolisib . fulvestrant Until PD, PIK3CA mutated, HR+, HER2- LA/mBC toxicity, R Prior CDK4/6 therapy death or 1:1 N 400 predefined LONG-TERM FOLLOW-UP Alpelisib . fulvestrant study end Stratification factors: visceral disease (yes vs. no), prior CDK4/61 therapy (adjuvant vs. metastatic setting) BREAST CANCER Primary endpoint: Secondary endpoints: PFS (BICR-assessed) os PFS2 ORR, BoR, CBR, DoR (all BICR-assessed) Safety and tolerability Fully enrolled --- [Slide 4] INAVO122: Phase 3 Inavolisib + PH FDC SC Ph3 in 1L HER2+, PIK3CA-mutated LA/mBC . Inavolisib HER2+, PIK3CA-mutated PH (IV or SC) . PH FDC SC maintenance Until PD, LA/mBC without prior . taxane toxicity, R treatment in the induction death or advanced setting 1:1 (4-6 cycles) predefined LONG-TERM FOLLOW-UP N=230 per SoC Placebo study end + PH FDC SC maintenance -28 to -1: Central biomarker assessment of HER2 and PIK3CA mutation (pre-screening) BREAST Stratification factors: Response to induction (CR/PR vs. SD); HR status (HR-positive vs. negative); de novo vs. relapsed disease CANCER 2026 Address Primary endpoint: Secondary endpoints: PFS (investigator-assessed) OS, ORR, DoR, PROs, safety, PK
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Gedatolisib, a pan-PI3K and mTORC1/2 inhibitor, with endocrine therapy in HR+/HER2-Adam Brufsky

Can dual PI3K/mTOR inhibition improve outcomes after CDK4/6i? @breastoncdoc of @UPMCHillmanCC reviews VIKTORIA-1: in PIK3CA-WT HR+/HER2- MBC, gedatolisib + palbociclib + fulvestrant achieved mPFS 9.3 vs 2.0 mo with fulvestrant (HR 0.24). #DAVABreast

VIKTORIA-1profile
2026 Kona Breast Cancer Summit slide — Adam Brufsky, Gedatolisib, a pan-PI3K and mTORC1/2 inhibitor, with endocrine therapy in HR+/HER2-2026 Kona Breast Cancer Summit slide — Adam Brufsky, Gedatolisib, a pan-PI3K and mTORC1/2 inhibitor, with endocrine therapy in HR+/HER2-2026 Kona Breast Cancer Summit slide — Adam Brufsky, Gedatolisib, a pan-PI3K and mTORC1/2 inhibitor, with endocrine therapy in HR+/HER2-2026 Kona Breast Cancer Summit slide — Adam Brufsky, Gedatolisib, a pan-PI3K and mTORC1/2 inhibitor, with endocrine therapy in HR+/HER2-
[Slide 2] Kaplan-Meier / survival curve — table and text data only
Primary Endpoint: Progression-Free Survival (BICR) Gedatolisib Triplet vs. Alpelisib + Fulvestrant in VIKTORIA-1 Study 2 Arm 0. Arm E: Gedatolisib . Alpelisib . Palbo Fulv Fulvestrant Median PFS, months (95% CI) Prograssione I Program * 2 worsed Adjusted HR (95% CI) 0.50 (0.37-0.68); P<0.0001 Fulvestrant Apelisit Fulvestant BREAST CANCER DATE Number - Risk Months Code . Patie Public Alpensis Fax 2026 ASCO #ASCO26 ---- - - MC FACP ASCO - APPROVAL MEETING
[Slide 1] The mechanism of gedatolisib and chemical structure creates optimized PK profile Results in lower rate of AEs typically associated with oral Pi3Ka, AKT or mTOR inhibitors¹ Gedatclisib is a100x more potent on live cells than oral single-target inhibitors of the PAM pathway Cycle (180 mg) 100000 (plasma) Enables it to achieve IC50 target inhibition at small fraction of concentration oral drugs require 13000 Effective concentration is >90% less than EC12 for normal cells' Gedatolisib remains above ICsc concentration for up to day 71 Enables infrequent dosing: 3 total doses per 28-day cycle (Days 1,8, 15) vs daily dosing for oral drugs Results in infrequent C... exposure I I I - - - 2000 100 - Occurs only 10-20% as often as oral drugs breat Carls Reduced incidence of disrupted glucose homeostasis I . 24 " # " BREAST 129 - - IV administration avoids first-pass exposure in key organs associated CANCER with AEs (e.g. liver and GI tract) - . The PK profile of IV gedatolisib results In less frequent dosing and Improved tolerability compared with oral, single-target inhibitors of the PAM pathway³⁴ - - : - --- [Slide 3] Pushing Beyond the 6-month PFS Ceiling after CDK4/6 Inhibitors Novel endocrine agents combined with targeted therapies represents the future of ET- based treatment in CDK4/6i-pretreated population 10 (ff $ IT AkTatered 6 4 2 0 - t - - Cevil Certify - - - - - - BREAST M - - - t--- - - - - - I CANCER IMAGE SIGNATURE (MILL) - i ! VICTORIA 2014 - - . Consider - --- [Slide 4] . VIKTORIA-1 Study Design HR+/HER2- Am 0 Gedatolsib - mg Y once - Advanced Breast Cancer - - - . Primary Endpoint Paltociclib 5 1 , Eligibility Criteria 21 - - if PFS (BICR) Pre- 5 postmenopausal women & men Fulvestrant 500 - - - 15 then - - Am D is Arm E Progression on/after CDK46 NSAI Arm E $2 lines of pnor ET for ABC STUDY 2 REST Alpelisib a 3 I I I , Secondary Endpoints Measurable doease, RECIST v1.1 PIK3CA-MT Fulvestrant 500 of - 1. days a bel - - 8 Screening result for PIK3CA status Arm F PFS BICR F n E) No T20M with HBATC >6.4% +6 or T1DM Response Assign Gedinalisib # 2 1 I No prior mTOR) PI3K, or AKTi % I 1 X Safety Fulvestrant 500 - then Qel BREAST No prior chemotherapy for ABC 3 CANCER Direfication Factors - centil ungiver nationalis years STUDY a KISS - ... - UNITED E T E E I I L $ . PIKJCA-WT Region USCanels - NOW) MKC - R / 49 Y. I - I - i 2026 ASCO BASCO29 ---- Sara A - MO. PACP ASCO
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Gedatolisib in PI3K mutant breast cancer: Ongoing trialsSara Hurvitz

What comes next for gedatolisib? Sara Hurvitz of @fredhutch reviews VIKTORIA-1 Study 2 in PIK3CA-mutated HR+/HER2- ABC: the gedatolisib triplet achieved mPFS 11.1 vs 5.6 mo with alpelisib + fulvestrant (HR 0.50; p<.0001). #DAVABreast

VIKTORIA-1profile
2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Gedatolisib in PI3K mutant breast cancer: Ongoing trials2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Gedatolisib in PI3K mutant breast cancer: Ongoing trials2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Gedatolisib in PI3K mutant breast cancer: Ongoing trials
[Slide 1] .......... .......... ......... ......... Gedatolisib Lifecycle Plan 2026-2031: Current and Planned ABC Indications ......... .......... ......................... ......... 2025 2026 2027 2028 2029 2030 2031 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 ......... ......... ---------- CLINICAL DEVELOPMENT ABC (HR+/HER2-) 2L PIK3CA WT (G + F +/-P) VIKTORIA-1 (approved Q3 2026) Commercially Available .......... ......... 2L PIK3CA MT (G+F+/-P) VIKTORIA-1 (pending approval Q2 2027) Commercially Available ......... 4TH SUMMIT ON 1L Endocrine Resistant (G + P + F) VIKTORIA-2 (ER) (potential approval Q4 2029) Commercially Available BREAST CANCER 1L Endocrine Sensitive (G + P + L) VIKTORIA-2 (ES) (potential approval Q1 2031) Commercialization 2026 HAWAII DAVAOneology BREASE CANCES 2L Sub-Q vs. IV (G + F) Phase 1 VIKTORIA-3 (potential approval Q3 '31) Fred Hutch Cancer Center Abbreviations: G, gedatolisib; P, palbociclib; F, fulvestrant; E; subQ, subcutaneous --- [Slide 2] Key Secondary Endpoint: Overall Survival (Interim Analvsis) VIKTORIA-1 Study 2 - N triplet Overall Survival (%) 40 " - " N - THE cutoff Gedatolisib 2026): half os of analysis 2027 nos Adjusted - ass in Ce) the Fulvesinant - 22.8 shit) gedatolisib Fulvestinant 21.1 BREAST CANCER and -Final survival Months 9 - , Number - Number Months Fred Hutch Cancer Center --- [Slide 3] Two Distinct First Line Trials VIKTORIA-2 (PIK3CA mutation or wild-type allowed) Arm A Primary Endpoint Eligibility Criteria 180 TO IV . I $ PFS . off 125 e 21 7. days off Study 1 Fulvestrant Days 18 15. I Endocrine every Indpoints: Resistant 11 05 440 more Arm 8 Ribeciclity ally 21 7 $ Safety Endocrine Status: Pulvestrant: & 15, then and every resistant (R) of (ET) Primary Endpoint Arm c possitive (II) 6 PFS (BICR) +12 BREAST 125 5 Study 2 CANCER Endocrine R Endports Sensitive to os 2026 - - Arm D 21 . days off Safety OIL Fred Mutch Cancer Center 274
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Targeting oncogenic KRAS in CDK4/6 inhibitor-resistant HR+ breast cancerAriella Hanker

So my favorite talk of the millions I saw today at #DAVABreast was @AriellaHanker’s on NF1 mutations driving driving RAS pathway activation in breast cancer and how Daraxsonrasib may overcome this! Fantastic talk and work! #KRAS #BreastCancer #MBC @DAVAOnc

Rebecca Shatsky, MDRebecca Shatsky, MD@Dr_RShatsky2026-08-20Source post on X ↗
PI3K pathway alterations and response to checkpoint inhibitors in mTNBCNeha Verma
Combining tucatinib with PI3K inhibitors in HER2+ BCElena Shagisultanova

Combining HER2 and PI3K pathway inhibition: Elena Shagisultanova of @JeffersonUniv reviews phase Ib tucatinib + alpelisib in HER2+/PIK3CA-mutated MBC. At the MTD, ORR was 56% and CBR 67%, including responses after prior tucatinib and T-DXd. #DAVABreast

2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Combining tucatinib with PI3K inhibitors in HER2+ BC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Combining tucatinib with PI3K inhibitors in HER2+ BC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Combining tucatinib with PI3K inhibitors in HER2+ BC2026 Kona Breast Cancer Summit slide — Elena Shagisultanova, Combining tucatinib with PI3K inhibitors in HER2+ BC
[Slide 1] Conclusions from phase I tucatinib - alpelisib clinical trial The combination of tucatinib and alpelisib had manageable toxicities at DL1 (tucatinib 300mg BID, alpelisib 250mg daily) which is an MTD TEAEs experienced by >50% of patients at DL1 were fatigue, nausea, weight loss, diarrhea, and rash Side effects were manageable with support medications and dose reductions of tucatinib and alpelisib No new safety signal has emerged from this drug combination. The combination showed significant antitumor activity: PR in 5 out of 9 evaluable patients (ORR 56%) and CBR of 67% (PR * SD>6 months) including responses post tucatinib and T-DXd. - Longest time on treatment was >3 years BREAST CANCER and Denna Combined blockade of HER2 and mutated PIK3CA is very promising. However, to make it a clinically viable strategy, we need to decrease toxicity --- [Slide 2] Enrollment and patient characteristics: 6 Data cutoff 12.05.2025 Screened: N=21 Patient characteristics N Screen fail: N=9 Median age (range). years 50 (range 33-66) Median number of lines of MBC therapy 2 (range 1-5) Enrolled: N=12 DL1 N=9; DL2 N=3 Prior HER2-targeted therapies: Trastuzumab, pertuzumab 12 Tucatinib 9 T-DM1 7 Off study: N=12 T-DXd 4 2 for toxicity Margetuximab 2 1 for patient decision 8 for PD Sites of metastatic disease 1 because of study closure Visceral MTS 10 BREAST (continued TUC/ALP/fulv off study) CNS MTS 6 CANCER DL Alpelisib Tucatinib DL2: 3/3 DLTs (diarrhea, mucositis, rash, 3/3 DL2 300mg daily 300mg BID creatinine increase, hypokalemia) 0/3 1/3 2/3 DL1 250mg daily 300mg BID DL1: 3/9 DLTs (diarrhea, fatigue, LFT elevation) DL1 was declared an MTD Fulvestrant was added in all HR+/HER2+ patients in standard dose --- [Slide 3] Alpelisib and tucatinib in HER2+ PIK3CA mutated MBC P MISSIN) Phase lb: Time-to-Event Optimal Interval Bayesian design N=9-19 patients; DLT window of 28 days Study schema: " Fulvestrant 500 mg IM* Enrollment Tucatine 300 mg PO BID" I Further 1 End of Screening cycles study Alpelise 250 no PO faily" Optional numer biopsy Cycle 1 Optional tumor biopsy Optional tumer biopsy Research blood sample Only in HR*/HER2+ patients Research blood sample Research blood sample Doses shown for DL1 Cohort Level Alpelisib Tucatinib Fulvestrant* - . BREAST Dose level -2 CANCER 200mg daily 200mg BID Dose level -1 250mg daily 250mg BID 500mg IM on 2026 MANAGE C1D1 and C1D15. Clinical trial inclusion criteria: Dose level 1 250mg daily 300mg BID and then q28 days HER2+ MBC with activating PIK3CA mutations Post-menopausal, or premenopausal patients on OFS Dose level 2 300mg daily 300mg BID One line of prior TKI for MBC is allowed including tucatinib "Fulvestrant added for patients with HR+/HER2+ MBC Patients with stable or progressing CNS disease not requiring immediate local therapy are included Degistration Adot 13021 ASCO 2024 --- [Slide 4] PIK3CA mutations are common in HER2+ BC HER2 HER3 Dataset Frequency of PIK3CA mutations NeoSphere study' 32% (133 out of 417 cases) MSKCC dataset 34% (86 out of 254 cases) METABRIC 32% (78 out of 247 cases) - - TCGA 29% (34 out of 119 cases) - - Cancer Genome Atlas2 up to 40% - - - - | - p85 p110g i $ POR PEN - I BREAST - INTOR CANCER 2026 PIK3CA mutations; Appear early in the course of the disease Lead to resistance to anti-HER2 monoclonal antiboides and HER2 TKIs Prior attempts to block the pathway: Everolimus: BOLERO-1, BOLERO-2: Buparlisib: PIK-HER2, NeoPhoebe Not biomarker selective, first-generation inhibitors, insufficient efficacy, high toxicity / Gamil 2. Cancer General - Nature 490(7418): 41-70 Minn - 5674-8 . 1 Signaing A Cancer Ass 3645-58 MSKK ME
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

TROP-2-Targeting ADCs

Moderator · Sara Hurvitz
AM5 of 6 with slides

Starting soon: TROP-2-Targeting ADCs; moderated by Dr. Sara Hurvitz (@FredHutch) #DAVABreast

2026 Kona Breast Cancer Summit — TROP-2-Targeting ADCs session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Panel@onnTROP2 directed ADCs in Breast Cancer #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — TROP-2-Targeting ADCs session
[Slide 1] BREAST CANCER SUMMIT DAVA Oncology davaone.com D SUMMIT ON BREAST CANCER 2026 DAVAOncology HAWAII CANCER MODERATOR DAVAOncology facilitating DAVAOncology successful drug development ...facilitating successful drug development & DAVAOnalog Oncology ology Signature blogy® DAVAOncolo AVAO DAVAOncology™ DAVAOncology DAVAOncology™ DAVAOncology™ DAVAOncology™ DAVAGHTS DAVAOrcology DAVAOncology™ DAVAOncology DAVAOncology™ DAVAOncology AVIOnse "AVAOrcedogy" DAVAOnalogy
VVinay Jain@VinayJaink9vh2026-08-19Source post on X ↗
ADC expression/target analysis and the current ADC landscapeEmanuel Petricoin

ADC Target and Response: Pre-treatment TOPO1 and TROP2 did not associate with response. Tumor MHCII did, as did the TOPO1 payload marker SLFN11. Sacituzumab delivers SN-38, which inhibits Topoisomerase I. Emanuel Petricoin from @GeorgeMasonU presented at #DAVABreast

2026 Kona Breast Cancer Summit slide — Emanuel Petricoin, ADC expression/target analysis and the current ADC landscape2026 Kona Breast Cancer Summit slide — Emanuel Petricoin, ADC expression/target analysis and the current ADC landscape2026 Kona Breast Cancer Summit slide — Emanuel Petricoin, ADC expression/target analysis and the current ADC landscape2026 Kona Breast Cancer Summit slide — Emanuel Petricoin, ADC expression/target analysis and the current ADC landscape
[Slide 1] APOLLO APOLL0-5 ADC DRUG TARGET MAPPING LARGEST PAN-TUMOR ADC PROTEIN DRUG TARGET ANALYSIS TO DATE 31 ADC PROTEIN TARGETS CO-QUANTIFIED ANALYZED ALK AXL B7H3 B7H4 MET Claudin18.2 EGFR FOLATE RECEPTOR ALPHA HER2 IGF1R HER3 LIV1 MESOTHELIN MUC-1 NAPI28 4TH SUMMIT ON NECTIN 4 BREAST PSMA CANCER ROR1 TF TROP2 2026 HAWAII CEACAMS A/Oncology" BRENET CANDER CD56 ADAM9 CL166 CADHERIN 6 TIM1 ENPP3 CD70 DELTA-LIKE PROTEIN 3 CLAUDIN 6 ROR2 --- [Slide 2] Breast share of cohort 5%) (20.5%) 46 K % ISHARD ACSTD2 TROP2 Total 34 METT was 7% 10.7% 187% / 5 were APOLLO-5 ADC DRUG TARGET MAPPING AIM NaPi2b/SLC34 Total_[D3V3] IMPLICATIONS AT THE BEDSIDE WHAT ADC TARGETS ARE OVER AND UNDER-EXPRESSED IN ADVANCED STAGE HER2- BREAST CANCER MJC1_Total_ID9O6 22.9% % west 299% 30.1% 30.5% we st 24.4% 1 12 will - wis 36.5% CD166_(ALCAM)_ [ARC1720] 30% 4 6% $ 76 2 a west %1.05 ADAM Total APOLLO 9 R R a O assign dog NPW ......... ......... ......... ........ / ........ ......... .......... ......... 2026 HAWAII GREAST CANCER . 4TH SUMMIT ON BREAST CANCER --- [Slide 3] and a TOPO1 PAYLOAD MARKER DID Sacituzumab delivers SN-38 the active metabolite of irinotecan that inhibits Topoisomerase I. SPONDENCE From predictive biomarker to therapeutic target: the dual role of High SLFN11 promotes: replication catastrophe, inability to SLFN11 in chemotherapy sensitivity recover from DNA damage apoptosis after SN-38 exposure. Tue Feng Yes / Thembes futuan Thang Received Unlike Topo1 expression itself, SLFN11 reflects whether DNA Above damage becomes lethal. SUNIL . belicare to SLFN 11 total of - I The 1 daily comeleted with ON of all I p=0.002 - 45000 effects by - have) possibiliting Ex of physician Do - AIR I - The of and the I la the 35000 - productive - # 19 active to with the . the SLENH tool Requests SLENH Therapoutic BREAST Intensity Value 25000 4th SUMMIT ON - 15000 CANCER 2026 5000 HAWAII DAVAOnenlogy BRENET CANCER Residual Disease YES PCR --- [Slide 4] ......... ......... ......... / But. TUMOR MHCII DID .......... ......... : ......... .......... TUMOR EXPRESSION OF MHCII WERE PREVIOUSLY FOUND TO PREDICT PEMBROLIZUMAB AND DURVALUMAB RESPONSE CLINICAL CANCER RESEARCH CLINICAL IMMUNOTHERAPY Tumor-Specific Major Histocompatibility-II Expression ......... ......... ....... Predicts Benefit to Anti-PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast Cancer Paulo\ MeD - Sanched pro.05 p=0.02 pr0.02 HLA-DR HLA-E total HLA-B total - - 145000 90000 85000 140000 I 80000 I I 60000 70000 65000 ******** 60000 Intensity Value Intensity Value 50000 40000 40000 Intensity Value 45000 4TH SUMMIT ON BREAST 30000 25000 CANCER 20000 : 20000 10000 5000 2026 0 D HAWAII DAVAOneology" BREAST CANCER Disease PORTER PORTES ........ Residual
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
TROP-2 as a mechanism of forming tight-junction based barriers against immune accessLeif Ellisen

TROP2 and immune exclusion in TNBC: Dr. Leif Ellisen @MGHBreastOnc reported higher TROP2 linked to poor outcomes and reduced immune checkpoint blockade response; anti-TROP2 + anti-PD1 synergized in a humanized TROP2 model. #DAVABreast

2026 Kona Breast Cancer Summit slide — Leif Ellisen, TROP-2 as a mechanism of forming tight-junction based barriers against immune access2026 Kona Breast Cancer Summit slide — Leif Ellisen, TROP-2 as a mechanism of forming tight-junction based barriers against immune access2026 Kona Breast Cancer Summit slide — Leif Ellisen, TROP-2 as a mechanism of forming tight-junction based barriers against immune access2026 Kona Breast Cancer Summit slide — Leif Ellisen, TROP-2 as a mechanism of forming tight-junction based barriers against immune access
[Slide 4] Kaplan-Meier / survival curve — table and text data only
Increased TROP2 levels associated with poor outcomes and reduced response to immune checkpoint blockade TNBC Survival by TROP2 expression ICB response by TROP2 expression logrank P = 1.9e-05 PDCD1 TACSTD2 Probability EPCAM (Basal only by PAM50 using all datasets in kmplot.com) 4TH SUMMIT ON BREAST Expression Odd Ratios CANCER low Cohort 1 Cohort2 high HAWAII DAVAOncology BREASY CANCER Cohort 1: RECIST response to combination Pembrolizumab, Time (months) Carboplatin, and Nab-paclitaxel for mTNBC. Number at risk Cohort 2:T cell receptor clonotype expansion post pre-operative low high Pembrolizumab *p<0.05, **p<0.01. Mass General Brigham Mass General Cancer Center
[Slide 1] ......... ......... TROP2 mediates tumor progression via the immune microenvironment ......... ......... ......... ......... In vivo Bogang Wu Immunocompromised Immunocompetent p=0.02 15 ......... ......... ********* ......... A 4T1 Nude BALB/c p=0.0003 p=0.04 Tumor: KO WT Tumor Volume (mm³) C 300 WT n.s. Tumor Volume (mm³) D 150 WT: KO KO p<0.0001 CD3+ cells/total cells (%) 10 ......... ......... TROP2 50 kD 200 100 5 100 50 ACTIN -43 kD 0 0 0 7 11 13 15 17 19 21 8 10 12 15 17 19 21 WT KO WT KO Days Days 4TH SUMMIT ON Margin Core BREAST WT KO CANCER 2026 HAWAII DAVAOncology" BREASY LANCER ........ Wu B et al. J. Immunother. Cancer 2026 Mass General Brigham 111 Mass General Cancer Center --- [Slide 2] TROP2 expression in TNBC recapitulates its physiological role in claudin-mediated tight junction maintenance TROP2/Claudin 7 Interaction 4T1 Syngeneic orthotopic model WT KO MDA-MB468 HCC1806 IgG: TROP2 Claudin7 Input + Merged/DAPI Input + Input + Anti-Trop2: Input + + + + CLAUDIN7 - WT TROP2 ACTIN - - Tumor Gene Expression KO WT ON Cell_cell.contact zone BREAST Tight junction CANCER KO Leukocyte degranulation inflammation pathway Leukocyte mediated cylotoxicity 2026 HAWAII Immune espanse to tumor cell Lymphocyte.costimulation PD1 signaling NK mediated cytotoxicity T cell mediated cytotoxicity Th1.cylotoxic.module Positive regulation of cell kiling 2 1 0 1 2 Normalized Enrichment Score (NES) Mass General Cancer Center TROP2 ICD is dispensable for restoring tight junctions, immune exclusion and tumor progression Extracellular intracellular ECD CD KO+Full Length KO+ECDTM KO+Stuff Transmembrane p=0.035 600 Tumor Volume (mm KO+Stuff 50 p=0.24 p=0.0135 KO+Full Length p<0.0001 . 400 KO+ECDTM Claudin7 40 CLAUDIN7 (% total area) 30 20 200 10 : 0 Name KO+ FL ECDTM Stuff 0 9 13 16 19 21 23 Days after 4T1 injection BREAST CANCER KO+Full Length KO+ECDTM KO+Stuff p=0.009 40 HAWAII CD3' cells/total cells (%) p=0.01 p=0.0059 2026 30 p=0.0036 20 10 - 0 KO+ FL ECDTM Stuff FL ECDTM Stuff Margin Core Mass General Cancer Center --- [Slide 3] --------- Anti-TROP2 synergizes with anti-PD1 for T cell recruitment and activation .......... ......... "Humanized" TROP2 model ......... Vehicle 400 aTROP2 A Total infiltrating CD3+ by IHC B Early activated CD8+ by flow cytometry Tumor Volume (mm³) 300 aPD1 p<0.0001 20 Vehicle ......... p=0.048 p=0.0124 aTROP2+aPD1 100 200 CD3+ cells/total cells (%) aTROP2 p=0.3 p=0.0027 15 p=0.0012 aPD1 TIM3 (%CD8*PD1*) 80 p=0.5013 100 10 aTROP2+aPD1 60 40 0 5 11 14 17 20 23 20 4ᵀᴴ SUMMIT ON BREAST Days post injection (Trop2 KO+hTROP2) 0 0 Margin Core CANCER ANN-TROP2 Vehicle aTROP2 aPD1 2026 HAWAII Input DAVAOncology 96, Anti- BREAST CANCER WT TROP2 TROP2 CLAUDIN7 Actin ACTIN Mass General Brigham ⑉ Mass General Cancer Center
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Sacituzumab govitecan in first line TNBC (ASCENT-03 trial)Kelly McCann
ASCENT-03profile
Sacituzumab govitecan in newly diagnosed or previously treated HR+/HER2- MBC (TROPiCS-02 and ASCENT-07)Joyce O'Shaughnessy

Sacituzumab govitecan in HR+/HER2- MBC: TROPiCS-02 showed SG improved PFS and OS; in ASCENT-07, median BICR PFS was 8.3 vs 8.3 mo and DOR 12.1 vs 9.3 mo, with OS immature. Presented by Dr. Joyce O'Shaughnessy @BCJoyceO, Baylor College of Medicine at #DAVABreast

ASCENT-07TROPiCS-02
2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Sacituzumab govitecan in newly diagnosed or previously treated HR+/HER2- MBC (TROPiCS-02 and ASCENT-07)2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Sacituzumab govitecan in newly diagnosed or previously treated HR+/HER2- MBC (TROPiCS-02 and ASCENT-07)2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Sacituzumab govitecan in newly diagnosed or previously treated HR+/HER2- MBC (TROPiCS-02 and ASCENT-07)2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Sacituzumab govitecan in newly diagnosed or previously treated HR+/HER2- MBC (TROPiCS-02 and ASCENT-07)
[Slide 2] Kaplan-Meier / survival curve — table and text data only
ASCENT-07 (Phase 3): Efficacy, PFS Primary endpoint: PFS by BICR TPC (n = 234) SG (n = 456) TPC (n = 234) Censored in first 4 mo, n (%) Median PFS, mo (95% CI) Started new anti-cancer Stratified HR (95% CI) Probability of progression-f free survival (%) therapy P-value* Received ADC as next 6-month PFS rate, % (95% CI) 71 (66-75) 64 (57-71) Ine treatment 12-month PFS rate, % (95% CI) 40 (35-45) 37 (29-44) PFS among subgroups was generally consistent with the overall population No. risk (events) Time (months) TPC Secondary endpoint: PFS by INV SG (n = 456) TPC (n . 234) 4TH SUMMIT ON Median PFS, mo (95% CI) BREAST CANCER HAWAII BREASY CANCER Probability of progression free survival (%) Stratified HR (95% CI) Nominal P-value* 6-month PFS rate, % (95% CI) 69 (64-73) 58 (51-64) 12-month PFS rate, % (95% CI) Oncology No risk (events) Time (months) TPC Jhaveri KL, et al. SABCS 2025. Abstract GS1-09
[Slide 3] Kaplan-Meier / survival curve — table and text data only
n (%)SG (n=348)TPC (n=203)
Without subsequent anticancer therapy66 (19)43 (21)
With with subsequent anticancer therapy282 (81)160 (79)
ADC91 (32)97 (61)
T-DXd83 (29)66 (41)
SG1 (0.4)29 (18)
Dato-DXd03 (2)
Other ADC8 (3)7 (4)
Chemotherapy238 (84)106 (66)
Targeted therapy65 (23)24 (15)
Endocrine therapy42 (15)24 (15)
Immunotherapy10 (4)3 (2)
All other5 (2)3 (2)
ASCENT-07 (Phase 3): Efficacy, OS and tumor response TPC (n=234) os at primary analysis (27% maturity) ORR, % (95% CI) Stratified OR (95% CI) Best overall response, n (%) Probablity survival of overall (%) TPC (n . 234) Median os, mo (95% CI) NR (NR-NR) NR (19.7-NR) 61% of participants in the TPC group SD ≥ 6 months received an ADC following treatment discontinuation Nominal P-value* Clinical benefit rate, % (95% CI) No at risk [evente] Responders, n Time (months) TPC (n=77) TPC Median (range) time to response, months Subsequent anticancer therapy Median DOR, months (95% CI) TPC (n=203) 4ᵀᴴ SUMMIT ON Any grade Grade 23 Grade 3 # Any grade BREAST Without subsequent anticancer therapy Neutropenia CANCER With with subsequent anticancer therapy Alopecia Nausea ADC Dianhes G-CSF TPC T-DXd Fatigue prophylaxis, n(%) HAWAII Anemia Primary Dato-DXd Constipation Secondary Other ADC Leukopenia Chemotherapy ALT increase TPC Targeted therapy Vomiting Endocrine therapy AST increase Immunotherapy Decreased appetite All other Hand foot syndrome TEAEs', Jhaveri KL, et al. SABCS 2025. Abstract GS1-09
[Slide 1] ASCENT-07 (Phase 3): 1L sacituzumab govitecan VS chemo after ET among HR+/HER2-, advanced/metastatic breast cancer Aim: SG vers TPC among patients with HR+HER2-, locally advanced unresectable or metastatic breast cancer who have received prior ET and are candidates for 1L chemotherapy Locally advanced unresectable or Primary endpoint: Sacituzumab govitecan 10 mg/kg IV metastatic HR+/HER2- BC: Days 1 and 8, every 21 days PFS by BICR No prior chemotherapy for locally N 690 n = 456 Key secondary endpoints: advanced or metastatic HR+/HER2- BC R Measurable disease per RECIST v1.1 2:1 os Treatment of physician's choice Must have at least 1 of the following: ORR by BICR - Progression on ≥ 2 previous lines of ET + (capecitabine, paclitaxel, nab-paclitaxel)ᵇ QOL targeted therapy for mBC* n = 234 Other secondary endpoints SUMMIT ON - Progression <6 mo of starting 1L ET + Treatment continued until disease progression or unacceptable toxicity BREAST CDK4/6i for mBC PFS by INV Stratification factors: CANCER - Recurrence < 24 mo of starting adjuvant ORR by INV ET + CDK4/6i and no longer a candidate Duration of prior CDK4/6i for mBC (none VS â 12 mo vs > 12 mo) DOR by BICR and INV 2026 for additional ET for mBC HER2 IHC (HER2 IHC 0 VS HER2 IHC-low [IHC 1+ or IHC 2+/ISH-]) HAWAII DAVAChalogy SPEASY CANCER Geographic region (US/Canada/UK/EU VS ROW) Safety Jhaveri KL, et al. SABCS 2025. Abstract GS1-09 --- [Slide 4] .......... ......... ......... Sacituzumab Govitecan for HR+ HER2- MBC: ......... ......... ......... .......... ......... ASCENT-07 ......... ......... ......... ......................... Investigator-assessed TPC PFS shorter than BICR-assessed PFS -- Informative censoring by investigator on the TPC arm? .......... ......... Median PFS Investigator Central (BICR) SG 8.4 8.3 4TH SUMMIT ON BREAST TPC 6.4 8.3 CANCER 2026 HAWAII DAVAOncology BREAST CANCER Shorter TPC PFS on investigator assessment augmented PFS difference between the 2 arms
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Saci/pembro/XRT in oligometastatic TNBCAnna Schreiber

De novo oligometastatic TNBC trial concept: At #DAVABreast, Dr. @AnnaSchreiberMD of @CUHemeOnc presented a proposed phase II multimodality trial using systemic therapy, surgery and ablative RT, including SG + pembrolizumab.

2026 Kona Breast Cancer Summit slide — Anna Schreiber, Saci/pembro/XRT in oligometastatic TNBC2026 Kona Breast Cancer Summit slide — Anna Schreiber, Saci/pembro/XRT in oligometastatic TNBC2026 Kona Breast Cancer Summit slide — Anna Schreiber, Saci/pembro/XRT in oligometastatic TNBC2026 Kona Breast Cancer Summit slide — Anna Schreiber, Saci/pembro/XRT in oligometastatic TNBC
[Slide 3] Kaplan-Meier / survival curve — table and text data only
Rationale: Multi-drug neoadjuvant and adjuvant therapy significantly improved survival in the KEYNOTE-522 trial and SG is highly active in mTNBC A Overall Survival According to Treatment Group in the Intention-to-Treat Population Median Progression free Survival This Patients Events included Percentage of Patients Alive and Free SG - Pembrolizumab Percentage of Patients Pembrolizumab-chemotherapy from Disease Progression Chemotherapy+Pembrolizumab patients Stratified hazard ratio for disease progression or death, 0.65 with Stage SG-pembrolizumab Placebo-chemotherapy 4TH SUMMIT ON Chemotherapy+pembrolizumab III disease BREAST CANCER Months No. Risk (no. of events) SG+pembrolizumab HAWAII Months DAVAOncology BREAST CANCER Chemotherapy+ No. at Risk pembrolizumab Pembrolizumab-chemotherapy Placebo-chemotherapy ASCENT-04 Trial, Tolaney Schmid et al, NEJM. 2024. et al, NEJM. 2026.
[Slide 1] .......... ......... ......... ......... ......... - ......... We hypothesize that all three treatment ......... ......... ......... modalities will be needed to eradicate Stage IV de novo oligometastatic disease. Surgery and ......... ......... ablative radiation will ensure there is no viable macroscopic cancer while multi-drug systemic 4TH SUMMIT ON BREAST therapy will eradicate micro-metastatic disease. CANCER 2026 HAWAII DAVAOncology BREAST CANCER ........ --- [Slide 2] --------- ......... ......... ......... ......... .......... ......... ......... .......... ......... We propose a multi-center phase II trial of .......... definitive therapy including sacituzumab govitecan and pembrolizumab in de novo ........ oligometastatic triple-negative breast cancer 4TH SUMMIT ON BREAST CANCER 2026 HAWAII DAVAOncology BREAST CANCER ........ --- [Slide 4] ......... .......... ......... ......... --------- TM CRITERIUM ABRCC Full-Service Contract Research Organization Academic Breast Cancer Consortium © 2025 ......... ......... ......... .......... ......... Trial Schema Step 2 Step 1 Resection of the Systemic primary tumor adjuvant therapy ......... ......... ......... Neoadjuvant At least partial followed by post surgery: induction Stage IV TNBC response to radiotherapy for therapy: initial therapy locoregional Oligometastatic Sacituzumab Primary Endpoint: 2 yr OS control + 1-5 metastatic lesions Govitecan + Secondary Endpoint: 2 yr PFS Carbo+Taxol ablative RT to No CNS disease pembro 8 cycles +pembro x 4 metastatic Treatment naive ......... ......... cycles lesions Any CPS score + AC pembro x4 cycles No response or Registry to follow survival q 6 months progression ........ 4TH SUMMIT ON BREAST End of C1D1 of C1D1 C101 C4D1 SG C7D1 SG . Adjuvant CANCER Enrollment 2 years carbo/taxol of AC Prior to surgery/radiation pembro pembro pembro therapy (EOS) 2026 HAWAII DAVAOncology BREAST CANCER ctDNA monitoring Tumor imaging ........ Statistical assumptions and sample size: Anticipated 2-year OS 60%. Null survival 35% based on all-comer 2-year OS in KEYNOTE-355 pembro arm. Accrual time: 2 years, follow-up time: 2 years. For 80% power with a one-sided alpha - 0.05, N=22 patients. Anticipate 4 participating sites. GILEAD
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
Employing UGT1A1 to determine optimal dose of sacituzumabSandra Swain

UGT1A1 and sacituzumab govitecandosing: Dr. @SandraSwainMD of @gumedcenter reviewed higher toxicity and earlier neutropenia in UGT1A1 poor metabolizers, with testing, G-CSF or 25% dose reduction considered before/with SG. #DAVABreast

2026 Kona Breast Cancer Summit slide — Sandra Swain, Employing UGT1A1 to determine optimal dose of sacituzumab2026 Kona Breast Cancer Summit slide — Sandra Swain, Employing UGT1A1 to determine optimal dose of sacituzumab2026 Kona Breast Cancer Summit slide — Sandra Swain, Employing UGT1A1 to determine optimal dose of sacituzumab2026 Kona Breast Cancer Summit slide — Sandra Swain, Employing UGT1A1 to determine optimal dose of sacituzumab
[Slide 2] Kaplan-Meier / survival curve — table and text data only
GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center Pooled analysis of TROPiCS-02, ASCENT, and IMMU-132-01 PFS and OS by CAVGᵢₐᵇ Quartiles CAVG CAVG LAB 1st Quartile 1st Quartile 2nd Quartie 2nd Quartil 3rd Quartie 3rd Quartile 4th Quartile TRUTT 4th Quartik PFS 4TH SUMMIT ON BREAST CANCER Time (months) Time (months) HAWAII Number at risk Number at risk DAVAOncology BREAST CANCER 1st Qarle72211100 1st Quartile 2nd Quartile 2nd Quartile 3rd Quartile 65 41 34 17 13 10 5 3 2 1 1 0 0 0 0 0 3rd Quartile 4th Quartile 4th Quartile CAVGlab total antibody average concentration Singh et al SABCS 2023, poster P01-04-06
[Slide 1] GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center ASCENT in mTNBC: Toxicity ≥ grade 3 in patients treated with sacituzumab govitecan by UGT1A1 status Table 4. Key treatment-related adverse events of all grades in >20% and of grade >3 in >5% of patients treated with sacituzumab govitecan significantly impacted by UGT1A1 genotype. TRAE2, (%) SG (n 243) *1/*1 wild type in 113) *1/*28 heterozygous (n - 96) *28/*28 homozygous In - 34) All grades Grade > 3 All grades Grade 23 All grades Grade >3 Hematologic Neutropenia 76 (67) 60 (53) 55 (57) 45 (47) 24 (71) 20 (59) Anemia 37 (33) 5 (4) 29(30) 6 (6) 16 (47) 5 (15) Leukopenia 18 (16) 10(9) 13 (14) 9 (9) 8 (24) 5 (15) BREAST Lymphopenia 10(9) (1) (5) (1) 4 (12) (6) CANCER Febrile Neutropenia 3 (3) 3 (3) $ (5) $ (5) 6 (18) 6 (18) 2026 Thrombocytopenia 3 (3) 0 6 (6) 0 4 (12) 4 (12) HAWAII Gastrointestinal Diarrhea 65 (58) 11(10) 57 (59) 9 (9) 21 (62) 5 (15) Rugo et al, npj Breast Cancer 2022;8:98 GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center TROPiCS-02 TEAEs by UGT1A1 status SG (n = 268) *1/*1 *1/*28 *28/*28 ......... Wild-type Heterozygous Homozygous (n = 103) (n = 119) (n = 25) All TEAEs, n (%) 103 (100) 119 (100) 25 (100) Grade > 3, n (%) 69 (67) 89 (75) 23 (92) TEAEs leading to dose SUMMIT ON 26 (25) 49 (41) BREAST reduction, n (%) 10 (40) CANCER TEAEs leading to treatment 70 (68) 76 (64) 19 (76) 2026 interruption, n (%) HAWAII TEAEs leading to treatment 5 (5) 7 (6) 3 (12) discontinuation, n (%) Marme, et al ESMO Breast 2023, Berlin Germany, Poster 194P --- [Slide 3] GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center Pooled safety analysis of TEAEs by UGT1A1 status in ASCENT, TROPiCS-02, TROPHY-U-01, IMMU-132-01 UGT1A1 Genotype* All Patients *1/*1 *1/*28 *28/*28 Safety, n (%) (N = 1063) (n = 416) (n = 420) (n = 112) All TEAEs 1060 (> 99) 415 (> 99) 418 (> 99) 112 (100) Grade 2 3 808 (76) 299 (72) 320 (76) 101 (90) DOMINIT ON AEs leading to dose reduction 205/661 (31) 69/268 (26) 89/270 (33) 30/76 (39) BREAST CANCER AEs leading to interruption 615 (58) 243 (58) 230 (55) 78 (70) 2026 78 (7) HAWAII AEs leading to discontinuation 27 (6) 27 (6) 8 (7) DAVADwalogy "Other genotypes, n = 13; genotype missing/not done, n = 102. "AEs leading to dose reduction not collected in IMMU-132-01; these patients were excluded from total. AE, adverse events; TEAEs. treatment-emergent adverse events; UGT1A1 UDP glucuronosyltransferase family 1 member A1. Rugo et al, ASCO 2024, poster 3029 GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center Pooled safety analysis of toxicities by UGT1A1 status in ASCENT, TROPiCS-02, TROPHY-U-01, IMMU-132-01 ≥ Grade 3 toxicity *1/*1 *1/*28 *28/*28 neutropenia 43% 49% 58% diarrhea 8% 12% 15% anemia 9% 12% 21% FUNMIT ON Febrile neutropenia 6% 5% 14% BREAST CANCER 2026 HAWAI Rugo et al, ASCO 2024, poster 3029 --- [Slide 4] --------- GEORGETOWN Lombardi Comprehensive UNIVERSITY Cancer Center ......... ......... ......... Trodelvy FDA label 6/2026: Warnings and precautions ......... Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia following initiation of .......... TRODELVY. (5.5) --------- The median time to first neutropenia including febrile neutropenia was 9 days in patients homozygous for the UGT1A1*28 allele, 19 days in patients heterozygous for the UGT1A1*28 allele, and 21 days in patients homozygous for the wild-type allele. UGT1A1 Inhibitors or Inducers: Avoid concomitant use. SN-38 is a UGT1A1 substrate. Concomitant 4TH SUMMIT ON BREAST administration of TRODELVY with inducers (carbamazepine) of UGT1A1 may reduce exposure to CANCER SN-38 and inhibitors (indinavir and atazanavir) increase exposure 2026 HAWAII DAVAOecology BREAST CANCER Adapted from FDA Label 6/2026
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Neoadjuvant and Adjuvant HER2+ Breast Cancer

Moderator · Dennis Slamon
AM4 of 4 with slides

Starting soon: Neoadjuvant and Adjuvant HER2+ Breast Cancer; moderated by Dr. Dennis Slamon (@dgsomucla) #DAVABreast

2026 Kona Breast Cancer Summit — Neoadjuvant and Adjuvant HER2+ Breast Cancer session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗

Neoadjuvant and adjuvant on HER2 positive breast cancer #DavaOnc #Davabreast

2026 Kona Breast Cancer Summit — Neoadjuvant and Adjuvant HER2+ Breast Cancer session
[Slide 1] DAVAOncology R DAVAOncology DAVAOncology ...facilitating successful drug development ...facilitating successful drug development ...facilitating successful drug development KONA BREAST CANCER SUMMIT in & DAVA Oncology davaonc.com SUMMIT ON REAST CANCER 2026 HAWAII BREAST CANCER MODERATOR DAVAOncology Oncolog ...facilitating successful drug development ...facilitating DAVAOncology successful drug development cology™ / Oncology drug ology NAOs DAVAOncology™ DAVAOncology DAVAOncology™ DAVAOncology™ DAVAOncology™ DAVAGGY DAVAOrcology DAVAOncology® DAVAOncology DAVAOncology™ DAVAOncology™ VIOnzing WADn-dogy"
VVinay Jain@VinayJaink9vh2026-08-19Source post on X ↗

Dr. @royaryam from @OSUWexMed presents a large HR+/HER2- early BC analysis: among pts receiving adjuvant chemotherapy, ILC had worse OS vs IDC overall (aHR 1.20), while outcomes were similar in low- and high-Oncotype DX groups #DAVABreast

2026 Kona Breast Cancer Summit — Neoadjuvant and Adjuvant HER2+ Breast Cancer session2026 Kona Breast Cancer Summit — Neoadjuvant and Adjuvant HER2+ Breast Cancer session2026 Kona Breast Cancer Summit — Neoadjuvant and Adjuvant HER2+ Breast Cancer session
[Slide 1] Kaplan-Meier / survival curve — table and text data only
Survival Analysis Survival Analysis of ILC VS IDC patients who received adjuvant chemotherapy with Number of Subjects at Risk . Censored Logrank D.K. -- -- 0001 Overall Survival SUMMIT ON BREAST CANCER HAWAII CAREES Time to Death (n months) Histology Type 1. Invasive Ductal Carcinoma 2 Invasive Lebular Carcinoma ILC IDC 5-year OS 10-year os The James THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER
[Slide 2] Survival Analysis Based on Oncotype Dx Scores ILC VS IDC patients who received adjuvant ILC vs IDC patients who received adjuvant chemotherapy & low oncotype chemotherapy & intermediate oncotype With Number of futjerts affers with Number Subjects Use 1.0 Censered 10 Censored Lograna pet Lograns - .. " 11 11 11 I Owner I Owner " 14 #2 #2 :: :: ------------------------- ON - 4007 : 2009 2004 1136 379 / 17419 WAST 10602 - ! - 1065 N - - - 977 - - - - 2403 - - not - BREAST 0 24 43 72 и 120 144 168 : 24 " 72 и 120 144 168 CANCER Time 16 Death in months) Time to Death in months) Histology Type Histology Type 2026 Invaste Durtal massve Liberar invasive Dure Caronoma 2 Ilvasive Lotter HAWAII ILC IDC ILC IDC 5-year os 96.1% (94.7%- 97.1% (96.5%- 5-year OS 96.0% (95.1%- 97.0% (96.8%- 97.2%) 97.6%) 96.6%) 97.3%) 10-year os 88.1% (85.1%- 90.4% (89.2%- 10-year os 87.6% (85.9%- 90.6% (90.0%- 90.5%) 91.5%) 89.1%) 91.2%) The James THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER 146 --- [Slide 3] Association Between Histology Type and Overall Survival Among Patients with Receipt of Adjuvant Chemotherapy Cohorts (Reference aHR (95% CI) P-value IDC)* Overall ILC cohort 1.20 (1.16-1.25) <0.001 ILC W low RS 1.04 (0.80-1.37) 0.76 ILC W intermediate 1.23 (1.06-1.43) 0.008 RS ** SUMMIT ON BREAST ILC W high RS 0.99 (0.86-1.14) 0.91 CANCER ILC W unknown RS 1.22 (1.17-1.27) <0.001 2026 HAWAII *Adjusted for age, race, ethnicity, Charlson-Deyo Score, Clinical T stage, Clinical N stage, grade, radiation and hormone therapies. The James THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER 148
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
T-DXd in patients with residual disease post neoadjuvant therapy (DESTINY-Breast05)Mark Pegram

DESTINY-Breast05 in HER2+ eBC: Dr. Mark Pegram (@StanfordMed) presents T-DXd vs T-DM1 for residual invasive disease post-neoadjuvant therapy. IDFS HR 0.47, 3-yr IDFS 92.4% vs 83.7%; adjudicated ILD 9.6% vs 1.6%. #DAVABreast

DESTINY-Breast05profile
2026 Kona Breast Cancer Summit slide — Mark Pegram, T-DXd in patients with residual disease post neoadjuvant therapy (DESTINY-Breast05)2026 Kona Breast Cancer Summit slide — Mark Pegram, T-DXd in patients with residual disease post neoadjuvant therapy (DESTINY-Breast05)2026 Kona Breast Cancer Summit slide — Mark Pegram, T-DXd in patients with residual disease post neoadjuvant therapy (DESTINY-Breast05)2026 Kona Breast Cancer Summit slide — Mark Pegram, T-DXd in patients with residual disease post neoadjuvant therapy (DESTINY-Breast05)
[Slide 1] Kaplan-Meier / survival curve — table and text data only
T-DXd n 818T-DM1 817
Patients with events, n (%)51 (6.2)102 (12.5)
3-year IDFS, % (95% CI)92.4 (89.7-94.4)83.7 (80.2-86.7)
HR (95 % CI)0.47(0.34-0.66)
DESTINY-Breast05 Study Design: ADJUVANT STUDY A global, multicenter, randomized, open-label, phase 3 trial (NCT04622319) Key Eligibility Criteria T-DXd 5.4 mg/kg IV Q3W Primary endpoint Residual invasive disease in the breast and/or for 14 cycles IDFS axillary lymph nodes after neoadjuvant chemotherapy with HER2-directed therapy (NAT) 40-day safety follow-up Key secondary endpoint High-risk defined as presentation prior to NAT with: DFS Inoperable eBC (cT4,N0-3,M0 or cT1-3,N2-3,M0) Operable eBC (cT1-3,N0-1,MO) with axillary Other secondary endpoints node-positive disease (ypN1-3) after NAT for 14 cycles BMFI Centrally confirmed HER2+ (IHC 3+ or ISH+) eBC DRFI Safety ECOG PS 0 or 1 - SUMMIT ON Concomitant adjuvant ET was allowed per local practices BREAST If administered, RT could be initiated concurrent with study therapy or completed CANCER Stratification factors prior to initiation of study therapy (sequential) per investigator Extent of disease at presentation (inoperable, operable) ILD monitoring program for patients treated with RT HAWAII HER2-targeted NAT (single, dual) All patients had baseline non-contrast, low dose (LD) chest CT during screening CANCER Hormone receptor status (positive, negative) All RT patients (concurrent and sequential) had LD chest CT 6 weeks after start of Post-NAT pathologic nodal status (positive, negative) study therapy. then every 12 weeks while on therapy, and at 40-day follow-up Sequential RT patients had additional LD chest CT after completion of RT prior to start of study therapy Loibl S, et al. N Engl J Med 2026;394:845-857. T-DXd Primary Endpoint: IDFSᵃ Patients with events, n (%) 3-year IDFS, % (95% CI) P value Invasive Disease-Free Survival This trial was not powered to statistically assess difference at time points; 3-year data is exploratory/descriptive in nature T-DXd (n 818) Censor SUMMIT ON BREAST CANCER Time, months Number at Risk: HAWAII DAVA/Cology - CARDER T-DXd 818 788 781 776 771 768 758 753 731 684 634 544 440 380 370 275 218 212 129 92 90 46 14 14 0 0 0 0 53% reduction in the risk of invasive disease recurrence or death for T-DXd compared with T-DM1
[Slide 2] TEAEs in ≥20% of Patients (Either Arm) T-DXd T-DM1 Nausea 71.3 29.3 Constipation 32.0 16.2 Neutrophil count decreased 31.6 14.4 Vomiting 31.0 9.0 White blood cell count decreased 29.7 13.0 Grade 1 Fatigue 29.5 20.2 Radiation pneumonitis 28.8 27.0 Grade 2 Anemia 28.3 17.0 Grade ≥3 AST increased 25.6 50.2 SUMMIT OR BREAST ALT increased 23.7 45.3 CANCER Diarrhea 23.2 8.6 Platelet count decreased 21.2 49.8 2026 HAWAII Decreased appetite 20.0 10.0 Headache 15.8 20.7 Arthralgia 10.3 20.5 80 60 40 20 0 20 40 60 80 Overall Safety Summary T-DXda T-DM1ª (n=806) (n=801) Grade >3 TEAEs, n (%) 408 (50.6) 416 (51.9) Serious TEAEs, n (%) 140 (17.4) 109 (13.6) TEAEs associated with discontinuation, n (%) 144 (17.9) 103 (12.9) TEAEs associated with drug interruptions, n (%) 400 (49.6) 329 (41.1) TEAEs associated with deaths, n (%) 3 (0.4) 5 (0.6) Treatment-related deaths 2 (0.2) 1 (0.1) Treatment duration, median, mo 9.8 9.7 SUMMIT OR Patients completed 14 cycles (%) 72.3 76.3 BREAST ILD (adjudicated), n (%) 77(9.6) 13 (1.6) CANCER Grade >3 ILD 9 (1.1) 0 (0) 2026 Grade 5 ILD 2 (0.3) 0 (0) HAWAII LV dysfunction, n (%) 23 (2.9) 14 (1.7) In the T-DXd arm, causes of death (n=3) were 2 ILD/pneumonitis and respiratory tract infection (adjudicated as not ILD) In the T-DM1 arm, causes of death (n=5) were leiomyosarcoma of the uterus, aneurysm, non-neutropenic sepsis, ovarian cancer, and traumatic pneumothorax --- [Slide 3] .......... ......... ......... SAN ANTONIO CT Requirements for Identifying ILD and BREAST CANCER SYMPOSIUM® Radiation Pneumonitis, as Per Protocol UT Health AACR ......... ......... ........ ......... ......... - - - Mans Cancer Center Z Low-dose, non-contrast CT requirements: ......... ......... ......... Adjuvant RT initiated If sequential RT is administered after Sequential and concurrent Sequential and concurrent randomisation, study treatment should be initiated Chest CT prior to infusion for Chest CT at 40 (+7) days ......... no later than 21 days after last dose of RT Cycles 3, 7 and 11 follow-up 4TH SUMMIT ON BREAST Baseline Sequential only CANCER Chest CT during Additional chest CT after If any signs or symptoms of radiation-induced screening for pneumonitis or drug-induced ILD appeared, completion of radiotherapy 2026 additional chest CT were recommended HAWAII all patients and prior to 1st infusion DAVAOncology BREAST CANCER ........ Adjuvant radiotherapy timing (sequential or concurrent) showed no differences in adjudicated drug-related ILD Similar distributions of any grade adjudicated drug-related ILD events were observed with sequential and concurrent radiotherapy in both treatment arms: (T-DXd: 10.7% and 9.6.% VS T-DM1: 2.6% and 1.0%, respectively) Most patients with drug-related ILD had recovered or were recovering at the data cutoff; in the T-DXd arm, the proportion of patients who had recovered from ILD was higher among those who received concurrent RT compared with sequential RT (69.0% vs 58.8%) --- [Slide 4] MESSAGES: Only at DAVA Kona can you expect to learn mo Hippocrates than oncology 7. DB-05 demonstrates a 53% reduction in the ris invasive disease recurrence or death for T-DX compared with T-DM1 Concomitant radiation + T-DXd does not appe increase the risk of radiation pneumonitis - - th converse is also true Clinicians must do everything possible to avoi 4TH SUMMIT ON 51LDin a curative intent setting BREAST CANCER IIIII - ILD surveillance by high-res, non contrast, lov c 2026 HAWAII thoracic CT should be every bit as vigilant as c DAVAOncology BREAST CANCER MIND YOUR HEAD surveillance by ECHO is for HER2-targeted the Should DB-05 be given after DB-11? - Depends the response?
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-19Source post on X ↗
T-DXd followed by THP as neoadjuvant treatment for HER2+ BC (DESTINY-Breast11)Adam Brufsky

DESTINY-Breast11 in HER2+ early breast cancer: Dr. Adam Brufsky (@breastoncdoc) of @UPMCHillmanCC reviewed DESTINY-Breast11: T-DXd→THP improved pCR vs ddAC→THP(67.3% vs 56.3%), with early EFS data and safety findings. #DAVABreast

DESTINY-Breast11profile
2026 Kona Breast Cancer Summit slide — Adam Brufsky, T-DXd followed by THP as neoadjuvant treatment for HER2+ BC (DESTINY-Breast11)2026 Kona Breast Cancer Summit slide — Adam Brufsky, T-DXd followed by THP as neoadjuvant treatment for HER2+ BC (DESTINY-Breast11)2026 Kona Breast Cancer Summit slide — Adam Brufsky, T-DXd followed by THP as neoadjuvant treatment for HER2+ BC (DESTINY-Breast11)2026 Kona Breast Cancer Summit slide — Adam Brufsky, T-DXd followed by THP as neoadjuvant treatment for HER2+ BC (DESTINY-Breast11)
[Slide 2] Kaplan-Meier / survival curve — table and text data only
Number of patients at riskTimefromrandomization(months)
T-DXd-THP32131531330524822020818914193501420
ddAC-THP32030329628523119918716312472351410
EFS Hazard ratio At data cutoff (March 12, 2025), EFS event maturity was 4.5%; at final cutoff, maturity is predicted to be ~10%* Probability of EFS EFS events: 18/320 EFS events: 11/321 4TH SUMMIT ON BREAST CANCER Number of Time from randomization (months) patients at risk HAWAII T-DXd-THP 321 DAVAOncology™ BREAST CANCER ddAC-THP 320 An early positive trend in EFS was observed, favoring T-DXd-THP vs ddAC-THP The median duration of follow up was 24 3 months with T-DXd-THP and 23.6 months with ddAC-THP "Predicted maturity assumes that the observed EFS hazard ratio continues after data cutoff (March 12, Nadia Harbeck, MD congress DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
[Slide 1] DESTINY-Breast11 study A randomized, global, multicenter, open-label, Phase 3 study ********* (NCT05113251) Data cutoff: March 12, 2025 n=321 T-DXd* THP Recommended Primary endpoint Patient population 4+4 cycles post-neoadjuvant pCR (ypTO/is ypN0) by blinded Previously untreated central review treatment per study HER2+ eBC protocol Secondary endpoints HR-positive or n=320 HR-negative Randomized ddACt THPS Surgery pCR: radiotherapy and pCR (ypTO ypN0) by blinded concomitant trastuzumab * central review 1:1:1 4 + 4 cycles High-risk defined as: pertuzumab for up to 1 year EFS - 2CT3 and N0-3 or No pCR: radiotherapy and Safety cT0-4 and N1-3 T-DM1 for up to 14 cycles Pharmacokinetics and n=286 T-DXd* Inflammatory BC HR-positive: endocrine immunogenicity 8 cycles therapy Invasive disease-free survival Overall survival SUMMIT BREAST Stratification factors Health-related quality of life CANCER HR status: ER and/or Additional outcome The T-DXd alone arm closed on March 13 2024, following PR-positive or negative Independent Data Monitoring Committee recommendation measures 2026 HER2 status: (IHC 3+ or The reasons were multifactorial, including a lower pCR rate, low likelihood Residual cancer burden (RCB) HAWAII DAVADeslogy | ISH+ in the absence of that T-DXd alone would be superior to ddAC-THP. and the timing of surgery IHC 3+ status) High reselution computed tomography chest scans were performed every 4 ***** during treatment Dipneuments - suspected while receiving OKA treatment ⑉ interrupted and tall investigation completed Echocardiogram or multigated acquisition scans .... performed during screening (428 days prior na rendemization), during treatment (43 days before Cycle 5). and at end treatment to ...... with - expection traction might packs - mg/ml CW) institutions noting QTW) pertanati (NC no dose followed by 420 mg GOW) - (00 mg/ml G2W) cyclophosphamide 000 mg/ml Q2W) packase (to ng/et OW) trastuzume a mgkg loading case followed by mgkg performab 1840 loading dose followed by 420 mg G3W) the window for surgery - WORKS following administration the last fine recedent study treatment administered - part the patient's soc the investigation discribion ct clinical tumor viage ER estragen womptor, HC 40. mesitta disease ISM* the positive, N. nodel viage PR progestione receptor, GXW. every - 0M1 instrume antancine, YONG absence of riversive cancer in the treast and asiltory codes no absence of - and cancer in the treast and exitury Nadia Harbeck, MD congress DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author. Permission is required for re-use ********* pCR (ypTO/is ypN0): primary endpoint ITT population+ (primary endpoint) HR-positive HR-negative 16.1% 11.2% (95% CI 3.0, 28.8) Д9.1% 100 (95% CI 4.0, 18.3; P=0.003+) (95% CI 0.2, 17.9) 83.1 80 67.1 67.3 61.4 56.3 52.3 pCR (%)* 60 40 20 SUMMIT ON 216/321 180/320 145/236 123/235 69/83 57/85 BREAST 0 CANCER T-DXd-THP ddAC-THP T-DXd-THP ddAC-THP T-DXd-THP ddAC-THP 2026 HAWAII Neoadjuvant T-DXd-THP demonstrated a statistically significant and I clinically meaningful improvement in pCR vs ddAC-THP Improvement was observed in both the HR-positive and HR-negative subgroups For the ITT population treatment effects - estimated by the difference - PCR with 95% Cia and values based - the stratified Mattinen and Numbers method with strate weighting by sample - - Mantal Hanszel weights) Patients with valid records regarding pCR status for any reason - considered be responders (including but 1 I whom from the staty I Insure death before surgery tack of surgeral specimen, defined not evenuable by the central pathologist) Subgroup analyses ware understand "Dy birded central review, pCR responders were defined " patients who only received information injudy Peatment - least and Dues: and net DCR, two-sided Provide childed the 0.00 prespecified coundary ITT. Nadia Harbeck, MD congress DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author. Permission is required for re-use --- [Slide 3] TEAEs in at least 20% of patients in either arm T-DXd-THP (n=320)* ddAC-THP (n=312)* --------- Overall 98.1 37.5 55.8 98.7 Nausea 64.7 1.9 0.3 51.6 Diarrhea 58.8 5.9 3.2 54.2 Alopecia 47.5 0 0 49.0 Fatigue 41.3 0.6 2.2 54.8 Transaminases increased 34.4 5.0 3.2 33.7 Neutropenia 29.1 13.8 34.6 44.2 ********* 5 29.1 0.3 0 24.4 Constipation 28.8 0.9 0.6 21.2 Vomiting 25.9 1.3 1.6 20.8 Neuropathy peripheral 22.8 1.6 8.7 49.7 Any grade Anemia 18.4 0.3 1.0 27.6 Grade >3 SUMMIT ON Stomatitis BREAST 17.2 4.4 13.1 23.4 CANCER Leukopenial 100 80 60 40 20 0 20 40 60 80 100 Patients experiencing AEs (%) 2026 HAWAI I T-DXd-THP had fewer any-grade and Grade ≥3 hematological and fatigue events than ddAC-THP Aside from nausea, gastrointestinal toxicity was comparable between arms "Safety analyses included at patients - received - loast one tone of any study instructions, grouped term fatigue, authoris - and whergy persuped - transaminations increased expertate transament increased - increased - giverny transferate increased - function twet hepatic function abnormal and - function test recreased, grouped - neutroght count decreased and resultipents typesped - hemogican decreased - Nood - count decreased and - and hematocr decreased. Tgrouped - while blood cell count decreased and europeria TEAC. - emergent adverse event Nadia Harbeck MD congress DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author. Permission is required for re use. --------- Overall safety summary ********* n (%) T-DXd-THP (n=320)* ddAC-THP (n=312)* Any AE 314 (98.1) 308 (98.7) Grade >3 120 (37.5) 174 (55.8) Any serious AE 34 (10.6) 63 (20.2) AE leading to any dose reduction 58 (18.1) 60 (19.2) AE leading to any drug interruption 121 (37.8) 170 (54.5) AE leading to any treatment discontinuation 45 (14.1) 31 (9.9) Any AE with outcome of death1 2 (0.6) 2(0.6) AE of special interest Drug-related adjudicated ILD/pneumonitis 14 (4.4) 16 (5.1) Grade >3 2 (0.6) 6 (1.9) Grade 5 1 (0.3) 1 (0.3) Left ventricular dysfunction 4 (1.3) 19 (6.1) SUMMIT ON Grade >3 1 (0.3) 6 (1.9) BREAST Grade 5 0 0 CANCER AE leading He overa safety profile of T-DXd-THP was fa 11 (3.4) 8(2.6) 2026 HAWAII Grade ≥3 AEs, serious AEs, treatment interruptions, and left ventricular dysfunction I ILD incidence was low and similar in both arms High-reselution computed timography chest scans - performed every ***** during treatment If Dipneumanitis was suspected while receiving . OKA treatment ... interrupted and M investigation completed Echocardiograms W multigated inquisition scare were performed during screening (<28 days prior to randomization). during treatment (4) days before Cycle 5), and at and of treatment to ****** left ventricular ejection fraction Median total treatment curstion incia regiran - 24. months City THPS and 21 0 months ISIAC THP) "Safety analyses included patients who received - one dose any study Treatment DXA THE - death - cause (N+T) preumonts by the dependent LD Adjudication Committee (PATE NAC THP - investigator determined drug-related bacterial encephaits (not), drug-related preumonts adjudicated by the LD Adjudication Committee (n*1), defined - surgery not occuring when 3-6 works after the - cycle of recedurant treatment Nadia Harbeck, MD congress DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author, Permission is required for re-use. --- [Slide 4] T-DXd alone arm: efficacy summary On March 13, 2024, the T-DXd alone arm closed following Independent Data Monitoring Committee recommendation.* Patients who were still receiving T-DXd alone could remain on therapy or immediately switch to local SOC pCR rate EFS 1.0 T- ddAC- 94.4% % DXd THP (95% CI 96.7) (n=2 (n=320) EFS events 15/286 86) Probability of EFS 0.9 93.1% EFS events Primary analysis (95% CI 7. 95.8) 18/320 Switch to local SOC classified as non-pCR Hazard ratio 0.82 pCR 43.0 56.3 (95% CI 0.41. 1.62) At data cutoff (March 12. 2025). A (95% CI) -13.2 (-20.8, -5.4) EFS event maturity was 5.4% 0.8 Prespecified supplementary analysis 0 HOMMIT ON Switch to local SOC not automatically classified as non- 0 3 6 9 12 15 18 21 24 27 30 33 36 39 pCR Number of BREAST patients risk Time from randomization (months) CANCER pCR' 51.4 57.2 T-DXd alone 286 280 276 271 240 208 199 175 134 95 43 14 2 0 4 (95% CI) -5.8 (-13.4, 1.9) ddAC-THP 320 303 296 285 231 199 187 163 124 72 35 14 1 0 2026 HAWAII - T-DXd alone showed inferior but robust pCR compared with the five-agent ddAC-THP EFS data were similar for T-DXd alone and ddAC-THP Treatment effects - extirnated by the difference - PCR with 95% Cts besed on the stratified Mettinen and Nurminan's method with strate weighting by sample - - Mantal weights) Median curstion of blow vp - 24. norths (1 -OXE) : 23.8 months IMAC THP) Analysis - reported the ITT pripulation "The reasons - munifacture including - DCR - line a that are alrane would be superver - BAC THIP and the firming of surgery by timed central - Nadia Harbeck, MD DESTINY-Breast11 ESMO Content of this presentation is copyright and responsibility of the author. Permission is required for re-use Implications for Clinical Practice The size of the primary tumor is important S Under 2 cm, upfront surgery, if node negative, TH X 12, or TDM-1 X 17 Over 2 cm, or clinically N(+), NAT with TCHP (THP X 4 a new option) High risk (non-operable, bulk disease): T-DxD X 4, THP X 4 (why not the other way?) *** SUMIT ON If residual disease after TCHP, TDM-1 X 14 (low risk), T-DxD X 14 (high risk) BREAST CANCER If ER positive, RD, consider neratinib after TDM-1 2026 HAWA CompassHer2-TDM-1 +/- tucantinib (trial ongoing) -
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Zanidatamab in neoadjuvant HER2+ breast cancerTaiwo Adesoye

De-escalating HER2+ EBC: Dr. @T_AdesoyeMD (@UTMDAnderson) presents NeoZanHER, testing chemo-free neoadjuvant zanidatamab. pCR was concentrated in HER2-driven tumors, raising the question of which patients may respond to HER2-targeting alone. #DAVABreast

NeoZanHER
2026 Kona Breast Cancer Summit slide — Taiwo Adesoye, Zanidatamab in neoadjuvant HER2+ breast cancer2026 Kona Breast Cancer Summit slide — Taiwo Adesoye, Zanidatamab in neoadjuvant HER2+ breast cancer2026 Kona Breast Cancer Summit slide — Taiwo Adesoye, Zanidatamab in neoadjuvant HER2+ breast cancer2026 Kona Breast Cancer Summit slide — Taiwo Adesoye, Zanidatamab in neoadjuvant HER2+ breast cancer
[Slide 1] ......... .......... ......... ......... .......... NeoZanHER: Neoadjuvant Zanidatamab in HER2+ Early Stage Breast Cancer ......... ......... ......................... .......... ......... Initial cohort Zanidatamab* ......... ......... .......... Eligibility N 11 20mg/kg IV Q2W X 6 doses HER2+ Breast Cancer Adjuvant Surgery therapy per Any HR status physician's 1-3cm choice ********* ......... ......... cN0 Latter cohort Zanidatamab* N = 9 20mg/kg IV Q2W X 10 doses ........ Screening C1 C2 C3 or C5 C3 or C5 D1 -22 Post-op visit 4TH SUMMIT ON US/MRI US/MRI US/MRI WES/RNAseq BREAST HER2 IHC CANCER / 2026 HAWAII DAVAOncology BREAST CANCER STUDY ENDPOINTS ........ Primary: pathologic complete response (pCR) Secondary: RCB, Radiographic response, Safety/tolerability Exploratory: Tumor-based biomarkers of response * Patients with hormone receptor positive tumors received endocrine therapy at physician's discretion --- [Slide 2] .......... ......................... ......... Significant Tumor Regression Was Observed Early During Treatment .......... ......... ......... ......... ......... Ultrasound (N=20, Pre-/on-treatment) ......... ......... ......... Significant reduction in tumor size (p = 0.0005) Significant reduction in tumor volume (p<0.0001) ......................... .......... Among patients with preoperative US (N=17) 5 with complete radiographic response ........ 3 of 5 achieved pCR 4TH SUMMIT ON BREAST CANCER 2026 HAWAII MRI (N=17, Pre-/on-treatment) DAVAOncology BREAST CANCER ........ Significant reduction in tumor size (p = 0.009) Significant reduction in tumor volume (p=0.0001) --- [Slide 3] pCR was concentrated in HER2-driven tumors p=0.06 ERBB2 NGS status S 14 Of 6 tumors with pCR High-level amplification 0 Gan 12 100% with HER2 IHC 3+ ER882 expression log2(TPM+1) 10 4 with evaluable WES had ERBB2 amp 8 100% PAM50 HER2-enriched 6 Higher ERBB2 mRNA expression in pCR RCB-1/2/3 pCR pCR tumors compared with non-pCR (p=0.06) 0-1+(2) HER2 baseline 2+ (5) 4TH SUMMIT ON 1+(3) BREAST CANCER 2+(5) 2026 HAWAII DAVAOncology BREAST LANDER Post-treatment HER2 downregulation HER2 baseline 3+ (15) 3+(4) observed in residual disease pCR (6) --- [Slide 4] ......... ......... NeoZanHer: What do we still need to learn? ......... ........ ......... ********* Who can receive less Who needs more ......... Can we better predict ......... therapy? therapy? response? Can we identify patients who Can early response help Can we identify biomarkers of ......... may achieve excellent identify patients who may response and resistance? response with zanidatamab benefit from addition of alone? chemotherapy? 4TH SUMMIT ON BREAST CANCER 2026 HAWAII DAVAOncology BREASY CANCER ........ Next steps Expand clinical experience, ongoing translational analyses, longer follow-up
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Hypofractionated radiation before chemoimmunotherapy as neoadjuvant treatmentShane Stecklein

Immunogenic neoadjuvant RT in breast cancer: At #DAVABreast, Dr. Shane Stecklein (@shanestecklein) of @OHCancer reviewed PRECISE, P-RAD and Neo-CheckRay, including increased sTILs after pre-op RT and RT + immune checkpoint blockade.

Neo-CheckRayP-RADPRECISE
2026 Kona Breast Cancer Summit slide — Shane Stecklein, Hypofractionated radiation before chemoimmunotherapy as neoadjuvant treatment2026 Kona Breast Cancer Summit slide — Shane Stecklein, Hypofractionated radiation before chemoimmunotherapy as neoadjuvant treatment2026 Kona Breast Cancer Summit slide — Shane Stecklein, Hypofractionated radiation before chemoimmunotherapy as neoadjuvant treatment
[Slide 1] 2026 KONA 473 ......... ORLANDO HEALTH® BREAST CANCER SUMMIT --------- ......... Trials of Immunogenic Neoadjuvant Radiotherapy in Breast Cancer PRECISE ......... N=20 patients with operable HR+/HER2- breast cancer. Pre-operative (6-8 days before surgery) ......... boost targeting only the primary tumor. 7.5 Gy X 1 (n=10) 2.0 Gy x 5 (n=10) Pre-operative radiation significantly increased median sTILs at time of surgery (P=0.0037). 4TH SUMMIT ON BREAST 2 Gy X 5 7.5 Gy X 1 CANCER 80 80 2026 HAWAII 60 60 DAVAOncology BREAST CANCER sTILs (%) 40 sTILs (%) 40 20 20 0 0 Pre Post Pre Post Shaitelman et al., IJROBP, 2025 --- [Slide 2] 2026 KONA 474 ORLANDO HEALTH® BREAST CANCER SUMMIT ********* Trials of Immunogenic Neoadjuvant Radiotherapy in Breast Cancer TBCRC-053 (P-RAD) --------- N=96 patients with operable node-positive HR+/HER2- HER2- breast cancer. Treatment n=48 triple-negative Top TCI Quartile (%) YPNO (%) n=48 high-risk HR+/HER2- Untreated .......... 15/62 (25%) [Ref] Pembrolizumab Pem 5/16 (31%) 24% Targeted Pem+9Gy 6/16 (38%) 29% Breast RT Pem+24Gy 9/16 (56%)* 33% 4TH SUMMIT ON BREAST Triple 0Gy TNBC Negative CANCER (n=48) Treatment Top TCI Quartile (%) ypNO (%) or Neoadjuvant R 2026 High Risk 3Gy x3 Chemotherapy Untreated 15/62 (25%) [Ref] HAWAII DAVAOncology BREAST CANCER HR+/HER2- HR+ cohort: SCHONEY (n=48) Pem cT1c-4c, wTx12, ACx4 7/16 (44%) 73% cN+, MO 8Gy X 3 Pem+9Gy 12/15 (80%)* 88% WK 0 (C101) 2 8 14 21 24 Pem+24Gy 14/17 (82%)* 79% Gupta et al., SABCS 2025 (HR+/HER2-): Ho et al., ASCO 2026 (TNBC) --- [Slide 3] ......... ......... ORLANDO HEALTH® 2026 KONA 475 ---------- BREAST CANCER SUMMIT --------- .......... ......... ......... Trials of Immunogenic Neoadjuvant Radiotherapy in Breast Cancer Neo-CheckRay ......... ..... - N=147 patients with operable high-risk HR+/HER2- breast cancer. Randomization 1:1:1 (n 147) ......... ......... Received neoadjuvant Tx12-ddACx4 + iSBRT (8 NACT ISBRT NACT SBRT durvalumab NACT ISBRT durvalumab olectumab Gy X 3, delivered at the (No_ICI) (Single_ICI) (Double ICI) n 48 51 48 end of week 4) ± ........ durvalumab ± oleclumab. 4TH SUMMIT ON BREAST Total 416.7% (-0.33.7) PD-L1- PD-L1+ &2% (-29.2-33.3) OR 2.5(0.9-6.6) 60 P=0.059 60 60 OR 1.1.(0.3-41) CANCER 426.6% (8.9-44.2) OR 12.0 (1.4-102.2) A-5.3% (-35.4-24.9) 50 A12.7% (-3.6-29.1) 50 50 OR 0.8 (0.2-3.0) OR 2.1 (0.8-5.5) 324.7%(7.7-41.6) 38.9% pCR. % (95% CI) 40 P=0.133 2026 HAWAII pCR. % (95% CI) pCR,%(95%CI) 40 OR 11.0(1.3-93.0) pCR. % (95% CI) pCR,%(95%CI) 40 36.8% 33.3% 29.4% 28.1% 30% (15.2-58.5) 31.6% (16.4-61.4) DAVAOncology BREAST CANCER 30 (20-46.7) 30 30 (16.9-41.9) (12.5-43.7) (13.6-46.4) (10.7-52.5) 20 16.7% 20 20 ........ (6.1-27.2) 10 10 3.4% 10 (0-10.1) 0 8/48 15/51 16/48 THE 9/32 9/30 7/19 6/19 7/18 0 0 SBRT NACT . . - SBRT NACT . + - SBRT NACT + + - Durvalumab - Durvalumab - . Durvalumab - + Oleclumab - - - Olectumab - - Oleclumab - - - Caluwé et al., Nat Med, 2026
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KAT-6 Inhibitors in HR+ BC

Moderator · Kelly McCann
AM3 of 3 with slides

Starting soon: KAT-6 Inhibitors in HR+ BC; moderated by Dr. Kelly McCann (@DrKEMcCann, @UCLA)#DAVABreast

2026 Kona Breast Cancer Summit — KAT-6 Inhibitors in HR+ BC session
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Prifetastat (KAT6i) and KAT-SIS Ph III overviewDoris Makari

KAT6 inhibition in HR+/HER2− breast cancer: Dr. Doris Makari of @pfizer reviewed investigational prifetrastat + fulvestrant phase 1 data (ORR 37.2%, mPFS 10.7 mo) and KATSIS-1 phase 3 design. #DAVABreast

KAT-SIS
2026 Kona Breast Cancer Summit slide — Doris Makari, Prifetastat (KAT6i) and KAT-SIS Ph III overview2026 Kona Breast Cancer Summit slide — Doris Makari, Prifetastat (KAT6i) and KAT-SIS Ph III overview2026 Kona Breast Cancer Summit slide — Doris Makari, Prifetastat (KAT6i) and KAT-SIS Ph III overview2026 Kona Breast Cancer Summit slide — Doris Makari, Prifetastat (KAT6i) and KAT-SIS Ph III overview
[Slide 1] ......... .......... ......... ......................... Phase 1 Study: Efficacy - Tumor Size Change From Baseline Parts 1B and 2B (Prifetrastat 5 mg QD + Fulvestrant 500 mg) Percent Change in Tumor Size by Patient's Best Response' Combination --------- ......... ....... --------- ......... Most frequent TRAEs PF-07248144 5 mg QD + fulvestrant 500 mg 100 Progressive drease Stable disease 90 Partial (≥20%) (N=43) 80 partial 70 fulvestrant treatment 60 By Preferred Term, *indicates ongoing All grade Grade ≥3 50 .......... --------- ......................... Change from Baseline (Best Response) 40 n (%) of patients with 30 (100.0) 27 20 any adverse event 43 (62.8) 10 o G1: 24 Dysgeusia (55.8) 10 N/A -20 G2: 12 (27.9) -30 -40 Median FU: 16.4m (15.6, 16.7) --------- ......... -50 ORR: 37.2% (23.0, 53.3) G3: 17 -60 Neutropenia 28 (65.1) (39.5) -70 CBR: 55.8% (39.9, 70.9) G4: 3 (7.0) -80 mPFS: 10.7m (5.3, 13.8) -90 -100 Fatigue 19 (44.2) 1 (2.3) Patients Anemia 19 (44.2) 6 (14.0) ******** Percent Change in Tumor Size Over Time by Patient's Best Response' Leukopenia 14 (32.6) 5 (11.6) 140 4ᵀᴴ SUMMIT ON 130 Best Response 120 response Stable disease BREAST 110- disease Complete response Dysgeusia (most G1); no dose reduction or treatment 100 First occurence of CANCER 06 / discontinuation due to dysgeusia 80 70 60 Neutropenia, manageable with dose modifications; no febrile 2026 HAWAII Percent Change from Baseline Sum of Diameters for Target Lesions 50 40 30 DAVAOncology BREAST CANDER neutropenia observed 20 10 0 ........ -10 Discontinuations due to AE: 2 (4.7%) -20 -30 -40 -50 80% dose reduction due to reversible neutropenia (5 3 - 2 -1 mg -60 -70 QD) -80 90 -100 0 50 100 150 200 250 300 350 400 450 500 550 500 Prifetrastat is an investigational compound. Its safety and 0 2026 Pfizer Inc. All rights reserved. 483 Days efficacy have not been established. --- [Slide 2] .......... ......... Phase 1 Study: Efficacy - - Clinical Responses ......... ........ ......... Parts 1B and 2B (Prifetrastat 5 mg QD + Fulvestrant 500 mg) ......... ......... --------- Total 2L* 3L+' PIK3CA/AKT1/ PIK3CA/AKT1/ ESR1 WT ESR1 MT PTEN WT PTEN MT (N=43) (n=23) (n=20) (n=18) (n=24) (n=23) (n=19) Objective response (CR + PR), n (%) 16 (37.2) 7(30.4) 9 (45.0) 6 (33.3) 10 (41.7) 10 (43.5) 6 (31.6) ......... ......... 95% CI* 23.0-53.3 13.2-52.9 23.1-68.5 13.3-59.0 22.1-63.4 23.2-65.5 12.6-56.6 Duration of response, median NE NE 9.2 NE 9.2 NE NE (95% CI'), months (7.2-NE) (NE-NE) (5.8-NE) (12.0-NE) (5.8-NE) (9.2-NE) (5.5-NE) Clinical benefit response (CR + PR + SD >24 weeks), n (%) 24 (55.8) 11 (47.8) 13 (65.0) 10 (55.6) 14 (58.3) 14 (60.9) 10 (52.6) 39.9-70.9 26.8-69.4 40.8-84.6 30.8-78.5 36.6-77.9 38.5-80.3 28.9-75.6 95% CI+ PFS, median 10.7 13.8 10.7 10.9 10.7 13.7 7.3 4TM SUMMIT ON (95% CIˢ), months (5.3-13.8) (3.5-NE) (5.5-13.7) (3.5-NE) (5.3-16.5) (5.6-NE) (2.8-13.8) BREAST CANCER 2026 HAWAII DAVAOncology BREAST CANCER *2L therapy is defined as treatment following 1L CDK4/6i ET. ........ '3L therapy or later includes ET, targeted therapy, and/or chemotherapy in between lines of therapy. 'Clopper-Pearson method used. Brookmeyer and Crowley method used LL=first-line; 2L=second line; 3L==third-line or later; 71=protein kinase B gene 1; CDK4/6i=cyclin-dependent kinase 4/6 inhibitor; Cl=confidence interval; CR=complete response; ESR1=estrogen receptor 1; T=endocrine therapy; MT =mutant; NE=not evaluable; PFS=progression-free survival; PIK3CA=phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PR=partial response; PTEN=phosphatase and tensin homolog: QD=once a day; SD=stable disease; WT=wild-type. Mukohara T. et al. SABCS 2024 Poster P4-10-28 0 2026 Pfizer Inc. All rights reserved. 484 Prifetrastat is an investigational compound. Its safety and efficacy have not been established. --- [Slide 3] ASCO 2026 Data Updated Safety Results in Phase 1 TEAEs The most common TEAEs were dysgeusia (85.9%), neutropenia (68.5%), and anemia (53.3%) The most common grade 3/4 TEAEs were neutropenia (41.3%), anemia (17.4%), and leukopenia (12.0%) There were 2 grade 5 TEAEs, including disease progression (n : 1) and encephalopathy (n # 1), neither of which were treatment related TEAEs reported in >10% of patients by maximum grade Total Total TEAE, (%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 TEAE, (%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 (N=92) (N=92) Any 8 (8.7) 22 (23.9) 54 (58.7) 5(5.4) 2(2.2) 91 (98.9) Diarrhea 17 (18.5) 3(3.3) 0 0 0 20 (21.7) Dysgeusia 62 (67.4) 17 (18.5) 0 0 0 79(85.9) Nausea 14 (15.2) 5(5.4) 0 0 0 19(20.7) Neutropenia* 4 (4.3) 21 (22.8) 32 (34.8) 6(6.5) 0 63 (68.5) Decreased appetite 10(10.9) 5(5.4) 2(2.2) 0 0 17(18.5) Anemia Stomatitis 19 (20.7) 16(17.4) 0 15 (16.3) 0 0 49 (53.3) 1(1.1) 0 0 14 (15.2) 16(17.4) Dizziness Leukopenia' 10 (10.9) 2(2.2) 1 (1.1) 0 0 13(14.1) 5(5.4) 25 (27.2) 11 (12.0) 0 0 41 (44.6) Headache 11 (12.0) 2(2.2) 0 0 0 13(14.1) Fatigue 28 (30.4) 7(7.6) 4(4.3) 0 0 39 (42.4) ALT increased 17 (18.5) 11 (12.0) 2(2.2) 0 0 30(32.6) ECG QT prolonged 9(9.8) 1 (1.1) 1(1.1) 0 0 11(12.0) AST increased 18(19.6) 8(8.7) 2(2.2) 0 0 28 (30.4) Hypocalcemia 10(10.9) 1(1.1) 0 0 0 1(12.0) Thrombocytopenia³ 16(17.4) 7(7.6) 3(3.3) 0 0 26 (28.3) Hypoalbuminemia 8 (8.7) 2(2.2) 0 0 0 10(10.9) TRAEs The most common TRAEs were dysgeusia (84.8% [grade 1, 66.3%; grade 2, 18.5%]), neutropenia (68.5%), and anemia (50.0%) The most common grade 3/4 TRAEs were neutropenia (41.3%), anemia (15.2%), and leukopenia (12.0%) - No grade 5 TRAEs were reported Layman RM et al. Presented at ASCO 2026 May 29 June 2, 2006; Chicago, 11, USA Poster 182 *includes eutrepenia and neutrophil count decreased "includes anemia and hemoglobin decreased "Includes leukopenia and white blood cell count decreased *Includes thrombocytopenia and platelet count decreased AL *alanine aminstransferase; -aspartate aminotramferase; ECG=electrocardiagram, Extreatment emergent adverse event, TRAE=treatment related adverse event e 2024 Pfice - AS rights reserved 485 Prifetrastat is an investigational compound. Its safety and efficacy have not been established. ASCO 2026 Data Updated Safety Results in Phase 1 5 mg QD prifetrastat : fulvestrant 5 mg QD prifetrastat 1 fulvestrant (N=92) (N=92) TRAE, n (%) All grades Grade 23 TRAE, (%) All grades Grade 23 Dysgeusia 78 (84.8) 0 (0) Neutropenia 63 (68.5) 38 (41.3) Grade 2:17 (18.5) Febrile neutropenia 0 (0) 0 (0) Decreased appetite 11 (12.0) 1 (1.1) Dose modifications due to treatment-related neutropenia, n (%) Weight decreased 5(5.4) 1 (1.1) Dose interruptions 31 (33.7) Dose modifications due to treatment-related dysgeusia, n (%) Dose reduction 34 (37.0) Dose interruptions (1.1) Drug discontinuation 1 (1.1) Dose reduction 0 (0) First grade 3/4 neutropenia Drug discontinuation 0 (0) Median time to onset of 0.3 (0.0-3.3) Median time to onset of 4.1 (1.1-77.9) dysgeusia (range), months (range), weeks Median duration of dysgeusia 7.1 (4.8-9.7) Median duration (95% CI), 1.9(1.1-2.1) (95% CI), months* weeks* Dysgeusia was managed with supportive care, including patient education, weight Grade 3/4 neutropenia was reversible and well managed with dose monitoring, and nutrition consultation, as clinically indicated modifications (5-3->2-> 1 mg QD) and supportive care Dysgeusia did not lead to any treatment discontinuations or dose reductions No febrile neutropenia was reported Authors' conclusions: After extended follow-up of the phase 1/2a study, the RP3D of prifetrastat maintained a manageable safety profile when dose modifications and supportive care measures were implemented for AEs such as neutropenia and dysgeusia *Based on Kaplan Meier estimates includes neutropenia and neutraphil count decreased 'First event of grade 1/4 neutropenia per laboratory test results Leyman RM, et at Presented at ASCO 2026 N sadvens event, Circonfidence interval daily - Ovrrcommended phase dose, -treatment related adverse event May 29 June 2, 2026; Chicago, 1, USA Poster 182 0 2834 How - AS rights reserved - Prifetrastat is an investigational compound. Its safety and efficacy have not been established. --- [Slide 4] ......... ......... KATSIS-1 (NCT07062965): Phase 3 Study Design¹,² --------- Phase 3, open-label, randomized, multicenter trial NCT07062965 Currently recruiting Objective: To evaluate the safety and efficacy of prifetrastat + FUL in patients with HR+/HER2- LA/mBC Key Eligibility Criteria ********* >18 years old HR+/HER2- LA/mBC Prifetrastat 5 mg PO (QD C1 D1-28) + Primary Endpoints Prior CDK4/6i + ET in the fulvestrant 500 mg IM (C1 D1 and C1 D15, advanced/metastatic setting or in the PFS' ......... ......... then D1 of each cycle thereafter) adjuvant setting with documented progression during or within 12 months from last dose* R Secondary Endpoints Measurable disease per RECIST v1.1 or 1:1 nonmeasurable bone-only disease Everolimus 10 mg PO (QD continuously OS, OR, DOR,¹ CBR ECOG PS of 0 or 1 N=400 D1-28) + investigator's choice of ET: PK Fulvestrant 500 mg IM (C1 D1-15, then D1 Safety 4ᵀᴴ SUMMIT ON Exclude pts with PIK3CA/AKT/PTEN of each cycle thereafter) BREAST mutations Exemestane 25 mg PO (QD, continuously) CANCER 2026 Stratification Factors HAWAII БРЕНЬТ CANCER Investigator choice of endocrine therapy with everolimus (exemestane or fulvestrant) *Participants are eligible If they previously received CDK4/61 or IT 113 monotherapy or in combination for rechallenge therapy in the advanced or metastatic setting, and have received prior therapy targeting TSRI or Presence of visceral disease (Y or N) BRCA1/2 Per RECIST vi.1 1. Prior line of therapy (1L or 2L) 'By blinded independent central review BACAI/2-breast cancer gene Cocycle ChArdinical benefit rate CDKA/Bincyclin- dependent kinase 4/6 inhibitor; D-day DCR-duration of response ECOG PS-Eastern Cooperative Oncelogy Group performance status; receptor : thereoy EXE resemestare FUL -fulvestrant HER2+human epidermal growth factor receptor 2: receptor M-intramuscularly: breast cancer OR-objective response, OS-owerall survival PFS-progression-free survivel; PKipharmacekineties; PO-by mouth, daily Revandemised RECIST v1 1-Response Evaluation Criteria in Solid Tomors version 11 1. ClinicalTrials gov https://alinicaltriais.gov/stusfy/NCT07062965. Accessed January 26, 2026 2 Kalinsky K, et at SABCS Poster PSS-08-19 Prifetrastat is an investigational compound. Its safety and efficacy have not been established. D 2025 Pfizer inc. AS rights reserved 487
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MEN2312, a KAT6 inhibitorJessica Tao

From KAT6 biology to endocrine resistance: At #DAVABreast, Dr. Jessica Tao of @HopkinsMedicine reviewed MEN2312 in ER+/HER2− breast cancer, including activity in an ESR1-mutant, fulvestrant-resistant model and its phase 1 FIH study.

2026 Kona Breast Cancer Summit slide — Jessica Tao, MEN2312, a KAT6 inhibitor2026 Kona Breast Cancer Summit slide — Jessica Tao, MEN2312, a KAT6 inhibitor2026 Kona Breast Cancer Summit slide — Jessica Tao, MEN2312, a KAT6 inhibitor2026 Kona Breast Cancer Summit slide — Jessica Tao, MEN2312, a KAT6 inhibitor
[Slide 1] ......... JOHNS HOPKINS MEN2312 is a novel, potent, selective KAT6 MEDICINE ......... .......... inhibitor with oral bioavailability ......... MEN2312 showed potent KAT6 inhibitory activity and good MEN2312 showed dose-dependent antiproliferative effect, selectivity over other HAT family members correlated with inhibition of ERα expression ......... Radiometric Ac-CoA Assay HAT selectivity panel ICso (nM) 125 14-day Proliferation Assay KAT6A 5 100 125- KAT6B 10 % Inhibition 75 100 236 ZR-75-1 ......... KAT7 50 CAMA-1 Inhibition % 75 KAT8 1859 25 Cell Line ZR-75-1 CAMA-1 KAT6A KAT5 2533 KAT6A copy number variation 7 50 0 5 4TH SUMMIT ON KAT6B P300 >10000 -25 KAT6A expression (TPM) -35 ~55 25 BREAST KAT7 CBP >10000 0.01 0.1 - 10 100 1000 ICso (nM) 5.5 2.8 c. HAT1 CANCER >10000 ISM5043 conc. (nM) -25 NatD >10000 0.1 1 10 100 1000 10000 ISM5043 conc. (nM) GCN5 >10000 Normalized ERa and H3K23Ac levels 2026 ISM5043 conc. (nM) PCAF >10000 in ZR-75-1 cells after ISM5043 treatment HAWAII DAVAOncology BREAST CANCER 1000 333 111 37 12 4.1 1.4 0.5 110 H3K23Ac 90 Relative band Intensity (%) 70 H3K23Ac/H3 ZR-75-1 H3 EC50 36.81 nM 50 Era/GAPDH Following Menarini's in-licensing agreement, ISM5043 is now named MEN2312 ERa EC50 4.11 nM 30 GAPDH 10 Cai et al. ISM5043, a novel, potent, and selective KAT6 inhibitor for the treatment of ER+/HER2- breast cancer, SABCS 2023 1 10 100 1000 ISM5043 conc. (nM) --- [Slide 2] ......... JOHNS HOPKINS MEDICINE MEN2312 demonstrated robust tumor growth ......... ......... ......... inhibition in ER+ xenograft mouse models ......... ......... MEN2312 treatment overcame ET resistance and showed synergistic effects in an ESR1m, fulvestrant-resistant PDX model (ESR1 Y537S mut) without KAT6 amplification 500 20 ......... ......... TGI (%) 400 Day 28 Vehicle ........ Tumor volume (mm³) 300 44 ns Relative BW change (%) 10 ISM5043, 10 mg/kg, PO, QD 0 fulvestrant, 200 mg/kg, SC, QW 200 ISM5043, 10mg/kg, PO, QD + fulvestrant, 200 mg/kg, SC, QW SUMMIT ON -10 BREAST 100 127 ** CANCER Q=1.21 based on Jin's equation indicating 0 141 ** -20 synergism between ISM5043 and fulvestrant 0 7 14 21 28 0 7 14 21 28 2026 HAWAII Days after treatment start Days after treatment start DAVAOncology CANCER Following Menarini's in-licensing agreement, ISM5043 is now named MEN2312 Stemline Cai et al. ISM5043, a novel, potent, and selective KAT6 inhibitor for the treatment of ER+/HER2- breast cancer, SABCS 2023 A Menarini Group Company --- [Slide 3] ......... JOHNS HOPKINS EDICINE MEN2312 showed strong monotherapy activity ......... in a refractory ER+/HER2-BC PDX model Strong monotherapy activity in refractory ER+, HER2- PDX model derived from liver metastasis from a patient who progressed on multiple prior lines of chemo and ET (incl. letrozole plus palbociclib) 20 600 ISM5043 ISM5043 Vehicle 3mg/kg 10mg/kg TGI (%) 10 Tumor volume (mm³) 400 Day28 83.6 Rleative BW change (%) H3K23Ac 0 67.7 Histone3 200 Vehicle -10 4TH SUMMIT ON BREAST ISM5043, 3mg/kg, QD CANCER 0 -20 ISM5043, 10mg/kg, QD 0 7 14 21 28 0 7 14 21 28 2026 Days after treatment start Days after treatment start HAWAII DAVAOncology BREASY CANCER Following Menarini's in-licensing agreement, ISM5043 is now named MEN2312 Stemline Cai et al. ISM5043, a novel, potent, and selective KAT6 inhibitor for the treatment of ER+/HER2- breast cancer, SABCS 2023 A Menarini Group Company --- [Slide 4] JOHNS HOPKINS DICINE MEN2312 showed strong monotherapy activity ......... in a refractory ER+/HER2-BC PDX model MEN2312 showed favorable in vitro ADME properties and promising PK and safety profiles Studies ISM5043 MEN2312 didn't significantly inhibit ......... Caco-2 permeability (10⁻⁶ cm/s) >2.5 the hERG current in human Kinetic solubility (µg/mL) >60 embryonic kidney cells Metabolic Stability (MMS & HMS ) < 30% Qh in all species In vivo PK: half life (m/r/d/c/p) >4 h No significant adverse findings were observed in cardiovascular, Oral Bioavailability (F%) >90% across preclinical species 4TM SUMMIT ON BREAST CYP inhibition, TDI, CYP Induction Low risk respiratory or neurological functions CANCER hERG >30 µM 2026 Cerep44 0 hits @ 1 µM HAWAII DAVAOncology BREAST CANCER Screening Ames Non-mutagenic DRF toxicology studies MOS - 10 folds in 28-day r/d and 14-day mini-pig DRF Cai et al. ISM5043, a novel, potent, and selective KAT6 inhibitor for the treatment of ER+/HER2 breast cancer, SABCS 2023 Stemline Following Menarini's in licensing agreement, ISM5043 is now named MEN2312 A Menarini Group Company
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OP-3136, KAT6A/B-selective inhibitor in ER+ BCAntonio Giordano

KAT6 inhibition in ER+ BC: Dr. Antonio Giordano (@DanaFarber) presents OP-3136, a first-in-human oral KAT6A/B inhibitor. In monotherapy dose escalation across solid tumors: PR in 3/19 (15.8%), tumor reduction in 13/19 (68%), no DLTs, H3K23ac reduction. #DAVABreast

2026 Kona Breast Cancer Summit slide — Antonio Giordano, OP-3136, KAT6A/B-selective inhibitor in ER+ BC2026 Kona Breast Cancer Summit slide — Antonio Giordano, OP-3136, KAT6A/B-selective inhibitor in ER+ BC2026 Kona Breast Cancer Summit slide — Antonio Giordano, OP-3136, KAT6A/B-selective inhibitor in ER+ BC2026 Kona Breast Cancer Summit slide — Antonio Giordano, OP-3136, KAT6A/B-selective inhibitor in ER+ BC
[Slide 1] ......... ......... - OP-3136-001 study design ......... ......... ......... This phase 1 study includes dose Phase 1 OP-3136-101 study design¹ escalation of OP-3136 as PART 2: DOSE monotherapy (Part 1A) or in PART 1: DOSE ESCALATION Key Eligibility Criteria EXPANSION (Part 1A) combination with fulvestrant (Part PART Monotherapy PART 18 and Part 10 ........ ......... ......................... 1B) and palazestrant (Part 1C), Patients with advanced or followed by dose expansion. metastatic solid tumors In Part 1A (monotherapy), OP- Monotherapy ER+, HER2-ABC, 30 mg PART 1B: and in fulvestrant ......... ......... 3136 was administered orally QD mCRPC, or mNSCLC. 20mg combination in continuous 28-day cycles across 12mg dose multiple dose levels (2-45 mg). (nms) Disease progression on PART or intolerance to standard palazestrant ..... therapies. 3 mg ECOG PS 0-1. SUMMIT ON BREAST OBJECTIVES Primary: Safety and tolerability, RDE Secondary PK, ORR (CR PR). CBR (CR PR CANCER (monotherapy combination) SD 24 weeks). DOR 2026 HAWAII DAVAOncology BREAST LANDER ........ Here we present an analysis from the monotherapy dose-escalation cohort of the study. ABC, advanced breast cancer; BOIN, Bayesian Optimal Interval; CBR, clinical benefit rate: CERAN, complete estrogen receptor antagonist; CR, complete response; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; ER+, estrogen receptor positive; HER2-, human epidermal growth factor receptor negative; KAT6, histone mCRPC, metastatic Dana-Farber Cancer Institute cancer; mNSCLC, metastatic cell cancer; ORR, objective response PK, pharmacokinetics; PR, partial response; QD, RDE, recommended for expansion: SD, disease; selective estrogen determined. 1. --- [Slide 2] ......... ......... - Safety and tolerability There were no dose-limiting toxicities observed across the evaluated dose levels. ......... ......... ......... ......... Most TRAEs were grade 1 or 2; no grade 4 or 5 TRAEs were reported. TRAEs reported in ≥10% of patients (N=32) ********* - The most common TRAEs were dysgeusia, anemia, and neutropenia. TRAE Any grade, n (%) Grade 3, n (%) Dysgeusia* occurred in 26 patients (81%), including 18 with grade 1 (56%) and 8 (25%) with grade 2 events. No patients discontinued Any TRAE 31 (97%) 11: (34%) ......... treatment due to dysgeusia. Dysgeusia* 26 (81%) N/A .......... Neutropenia occurred in 11 patients (34%), including 9 (28%) with Anemia 12 (38%) 2 (6%) grade 3. No grade 4 neutropenia or febrile neutropenia (any grade) Fatigue 12 (38%) 1 (3%) were reported. No patients discontinued treatment due to neutropenia. Neutropenia⁺ Neutropenia was reversible and manageable by dose modifications. 11 (34%) 9 (28%) Nausea 8 (25%) 0 AEs, regardless of causality, leading to dose interruption Platelet count decreased 6 (19%) 0 SUMMIT ON occurred in 14 patients (43.8%), and dose reductions in 8 BREAST ALT increased 4 (12.5%) 0 CANCER patients (25.0%). The most common AE leading to dose Back pain 4 (12.5%) 0 reduction was neutropenia (12.5%). 2026 HAWAII DAVAOncology BREAST CANCER Overall, 21 patients (66%) discontinued treatment. 11 (34%) patients discontinued due to disease progression; 1 (3.1%) ........ discontinued due to grade 3 lower respiratory tract infection, not related to OP-3136; 9 (28%) patients discontinued due to other reasons (physician decision, clinical progression, and withdrawal of consent). *Includes preferred terms 'Dysgeusia' and Disorder. Dana-Farber Cancer Institute Includes preferred terms 'Neutropenia' and decreased. Grade patient and 30 6 mg. and leukopenia ALT. alanine aminotransferase; N/A. not applicable; TRAE. 512 --- [Slide 3] .......... ......... - Efficacy: Radiographic response --------- ......... ********* Computed tomography scans from patients with confirmed partial response Baseline Best response Patient with ER+, HER2-ABC; 4 prior lines for metastatic disease. - OP-3136 20 mg QD. Confirmed PR per RECIST 1.1 at ~20 weeks. 40% tumor reduction from baseline. Remains on treatment at ~30 weeks. ......... ......... Patient with mCRPC; prior apalutamide for metastatic disease. OP-3136 6 mg QD. Confirmed PR per RECIST 1.1 at ~20 weeks. 4TH SUMMIT ON -35% tumor reduction from baseline. BREAST CANCER PSA increased from ~7.0 to ~12.6 ng/mL, followed by decline and stabilization (~5-7 ng/mL). 2026 Remains on treatment at ~38 weeks. HAWAII DAVAOncology BREASY CANCER ........ Representative cases demonstrate confirmed PRs with radiographic tumor reduction. Dana-Farber Cancer Institute ABC, advanced breast cancer, ER+, estrogen receptor-positive; HER2-, human epidermal growth factor receptor 2-negative; mCRPC, metastatic castration-resistant prostate cancer; PR, partial response; 515prostate- specific antigen; QD. once daily; RECIST, Response Evaluation Criteria in Solid Tumors. --- [Slide 4] ......... ......... - Efficacy: Duration of treatment* ......... --------- ********* 2 mg 3 mg 6 mg 12 mg ********* ......... 20 mg ......... ......... 30 mg Treatment ongoing Progressive disease Partial response Advanced breast cancer Metastatic castration-resistant prostate cancer Metastatic non small cell lung cancer 45 mg 4TH SUMMIT ON BREAST I CANCER 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks on treatment 2026 HAWAII DAVAOncology BREAST CANCER ........ Longest duration of treatment is 62 weeks and ongoing; 11 (34%) remain on treatment, including 9 patients with ABC and 2 with mCRPC. Dana-Farber Cancer Institute *Each lane represents 1 patient. Progressive disease (PD) assessment date was used if end of treatment date was missing for patients with PD. Progression by radiographic assessment only. Data out-off 546 2026. ABC, advanced breast cancer, mCRPC, metastatic castration- resistant prostate cancer; mNSCLC, metastatic non-small cell lung cancer.
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Adapting TNBC Treatment Post-Neoadjuvant Therapy

Moderator · Mark Pegram
PM6 of 6 with slides

Coming up: a timely discussion on adapting TNBC treatment after neoadjuvant therapy. Moderated by Mark Pegram, MD, this expert-led session will explore evolving strategies, post-neoadjuvant decision-making, and key clinical considerations shaping care. Stay tuned! #DAVABreast

2026 Kona Breast Cancer Summit — Adapting TNBC Treatment Post-Neoadjuvant Therapy session
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Panel on T-cell repertoire #DavaOnc #Davabreast

2026 Kona Breast Cancer Summit — Adapting TNBC Treatment Post-Neoadjuvant Therapy session
[Slide 1] & & & & DAVAOncology DAVAOncology DAVAOncology & 8 R ...facilitating successful drug development facilitating successful drug development ...facilitating successful drug development & & KONA BREAST CANCER SUMMIT in DAVA Oncology davoonc.com 8 D & ON BREAST CANCER 2026 HAWAII DAVAOncology MODERATOR & DAVAOncology ...focilitating DAVAOncology successful drug development DAVA SUCCE facilitating successful drug development DMAOnalog Oncology cology Oncolog & DAVAOnd DAVAOncology™ DAVA DAVAOscology DAVAOncology® DAVAOncology DAVAOncology DAVAOncology IVAG DAVAOncology DAVAOndogy DAVAOncolo DAVAOncology WAOredogy DIVAOncology DAVAOncology
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Sacituzumab govitecan in mTNBC with residual disease after neoadjuvant therapy: ASCENT-05Mark Pegram

In TNBC with residual invasive disease after neoadjuvant therapy, the risk of recurrence remains substantial. Mark Pegram, MD, from @StanfordMed highlight the rationale and design of ASCENT-05/OptimICE-RD, evaluating sacituzumab govitecan + pembrolizumab in the post-neoadjuvant setting. #DAVABreast

ASCENT-05
2026 Kona Breast Cancer Summit slide — Mark Pegram, Sacituzumab govitecan in mTNBC with residual disease after neoadjuvant therapy: ASCENT-05
[Slide 1] Kaplan-Meier / survival curve — table and text data only
Keynote-522: 75-Month Follow Up Shows Poorer Antibody-Drug Conjugates as Trojan Horses: Overall Survival Outcomes for Non-Responders Yes - Homer, circa 8th century BCE pCR No Percentage of Patients Pembrolizumab-Chemotherapy Responder Placebo Chemotherapy Responder BREAST BREAST Pembrolizumab-Chemotherapy Responder CANCER CANCER Chemotherapy Non- Responder Time, months Siege of Troy (King Agamemnon vs. Achilles) No. at risk Metre Dactylic hexameter STUDY OF ACITUZUMAB GOVITECAN FOR RESIDUAL AFTER NEOADJUVANT CHEMOTHERAPY SURGERY GILEAD ESMO DAVAOncology ASCENT-05 / OptimICE-RD (AFT-65): Phase III, Randomized, Open-label, Study of Adjuvant Sacituzumab Govitecan + Pembrolizumab vs Treatment of Physician's Choice in TNBC Patients with Residual Disease After Neoadjuvant Therapy and Surgery Key Recent Updates to the Protocol Residual invasive TNBC in breast Key Study Endpoints Interval of up to 16 weeks (increased from 12) from surgery to registration and randomization, or positive node(s) after Sacituzumab Govitecan + Pembrolizumab neoadjuvant therapy and surgery during which radiation must have been completed cycles History of cT1,cN1-2 or cT2- Primary SG: 10 mg/kg IV on d and cycles 4, cN0-2 disease IDFS (IBCFS per STEEP v2.0) Radiation must be completed during this time Pembro: 200 mg IV cycles Received at least 6-cycles Secondary (or 18 weeks) of neoadjuvant Patients may not receive 'sandwich' chemo/XRT/chemo Long-term anthracycline- and/or follow up dfs taxane-based chemotherapy Treatment of Physician's Choice 8 cycles with or without an aPD-(L)1 RFS Patients may receive up to 3 doses (up from 2) of pembrolizumab in the post-op setting prior to Pembro: 200 mg IV on of 21 cycles agent or platinum agent Incidence of TEACs and clinical registration and randomization Pembro capecitabine: pembro 200 mg IV on laboratory abnormalities TNBC diagnosis: ER and plus capecitabine 1000 mg/m2 PO BID on d 21-d cycles TTW of QoL based on FACT-B PgR <10% HER2 negative TOI scores ALND strongly recommended for patients with (MICROmets) (still required for patients with BREAST per ASCO/CAP Exploratory Biomarkers BREAST MACROmets) CANCER gBRCA mutants excluded Stratification Factors: CANCER Trop-2. PD-L1 Prior aPD-(L)1 therapy (yes vs no); cap no. at approximately 10% TIL ctDNA ALND not required for patients ypTN0(i+) (nodal irradiation recommended) Treatment for Residual Prior anthracycline based therapy (yes vs no) Exploratory QoLs Disease Completed Pathologic nodal status at the time of surgery (ypNO vs ypN*) FACT-B PRO-CTCAE Windows for follow-up evaluations widened After 24 Weeks Geographic region (US vs East Asia vs RoW) EQ-5D-5L. FCRI-SF STUDY OF SACITUZUMAB GOVITECAN FOR RESIDUAL TNBC ASCO American society cirical ancology amprogramed death two daily pathologists day estrugen AFTER NEGADJUVANT CHEMOTHERAPY & SURGERY GILEAD DAVAOneology" (igand) American Cheese functional assessment cencer Pheracy treast FCRISE fear recurrence BIRCA permine breast tance gene HER2 epidemal youth factor recepter BCFS invoive treas cancer survive invasive tree sunnet N. reavenous os overall survival Perribes PO orally PR propesterone receptor ON quality - RoW the wont RFS recumence the survive SG govtecan STEEP standardized definitions for efficacy endorts TEACA Greatment-oment soverse events, TNBC breast cancer TO - culcome TPC treatment physician's chace TTW us Distes
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I-SPY2.2: Datopotamab deruxtecan + durvalumab in early-stage breast cancerRebecca Shatsky

I-SPY 2.2 data with Dato + Durva showed an overall pCR rate of 50% (53/106), reaching 79% in the Immune+ subtype. @Dr_RShatsky from @UCSanDiego highlighted that >50% of pCRs occurred with Block A alone and >90% by Block B, potentially avoiding taxane/anthracycline exposure. Toxicity was consistent with prior studies. #DAVABreast

I-SPY2
2026 Kona Breast Cancer Summit slide — Rebecca Shatsky, I-SPY2.2: Datopotamab deruxtecan + durvalumab in early-stage breast cancer
[Slide 1] Rationale: Dato + Durva in 1st line mTNBC ASCO 2024 New I-SPY 2.2 Design Features: Multiple Sequential Regimens Called Blocks Preclinical data have BEGONIA: Antitumor responses in 1st line Dato Durva for mTNBC3 demonstrated that Topo-I . inhibitors can enhance Block A Block B Block C Surgery Confirmed ORR: 79% (49/62; 95% CI, 66.8-88.3) antitumor immune Median PFS: 13.8 months; Median DoR: 15.5 months Investigational agents Optimal regimens Adriamycin/Cytoxan pCR and RCB responses and improve the antitumor efficacy of anti- besella without standard based on Response Adriamycin/Cytoxan endpoints chemo across RPS Predictive Subtypes 10 per SOC PD-L1 therapy1 (RPS) and SOC Investigational agents to improve response In the phase 1b/2 BEGONIA study, Dato + Durva had an ORR of 79% in 1st-line ATION ATION BREAST N=62 BREAST CANCER mTNBC³ AFTV CANCER Progressive I Stable disease Parsal I $ DATO-DxD Durva Taxol Carbo PD11 AC PD11 №106 N=66 №26 №20 Screen Randomize Surgery for be stated fue the All patients must Block A Block B Block screen Mammaprint cell High Risk to be №35 №35 eligible Surgery Surgery The The The Efficacy of Block A 0 Efficacy of treatment strategy HR-HER2-Immune-DRD- . spanning Blocks A-C - - Dato + Durva meets the graduation threshold in the Immune+ subtype . Overall rate of pCR: - 53 of 106 (50%) por Response Predictive Subtype N pCR non-pCR* Modeled Rate (95% CI) Threshold P(>Thr) 3% HR+Immune-DRD- 25 0 23 15% 0.00 (0%-7%) inmune DRD HR-Immune-DRD- 23 2 14 13% 15% 0.33 HAMER2 (3%-23%) 0.25 65% immune Immune+ 47 20 11 40% 0.99 (47%-83%) immune+ 24% Immune-DRD+ 11 3 6 40% 0.06 (4%-44%) " IPSA BREAST BREAST CANCER Receptor Subtypes N pCR non-pCR* Modeled Rate (95% CI) Threshold P(>Thr) CANCER HR+ 18% 42 4 29 15% 0.68 (6%-30%) HR- 64 21 25 44% 40% 0.74 (32%-56%) Includes Patients with Biopsy Positive for Invasive Cancer after Block Aor non-pCR or in subsequent blocks 125 0.50 1.00
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T-cell clonal diversity predicts response to neoadjuvant sacituzumab + PARPi in TNBCLeif Ellisen

NeoSTAR A2 data showed that neoadjuvant SG + pembrolizumab achieved pCR in 16/50 patients (32%) after 4 cycles in early TNBC. Dr. Leif Ellisen from @harvardmed highlighted TMB and HR deficiency as predictors of response, while an immune-poor TME was linked to resistance. No new safety signals were observed. #DAVABreast

2026 Kona Breast Cancer Summit slide — Leif Ellisen, T-cell clonal diversity predicts response to neoadjuvant sacituzumab + PARPi in TNBC
[Slide 1] NeoSTAR A2 Primary Objective: pCR with neoadjuvant SG/P RD: Residual disease Results: Primary Endpoint Surgery Study Schema Secondary Objectives: NACT: Neoadjuvant chemotherapy Need for additional NACT Radiographic response (RR) SG: Sacituzumab govitecan No RD suspected 16 pCR after SG/P only Rachel Abelman, Laura Spring, Safety and tolerability (adverse P: Pembrolizumab IBC: Inflammatory breast cancer N= 24 16/50, 32% Aditya Bardia events [AEs] per CTCAE v5.0) 2-year event-free survival (EFS) . 4 cycles of 8 RD Baseline 12 weeks Adjuvant Therapy SG/P N=50 Eligible pts: At 17 RD least T2 and/or SG at starting pCR: 4 cycles of taxane/carboplatin node positive early dose 10mg/kg D1/ with q3w P to complete year* TNBC (non-IBC) D8 and P 200mg per investigator discretion RD suspected (ER-*, PR-, HER2- Surgery 9 pCR after SG/P and per ASCO/CAP D1 of 21-day Additional Neoadjuvant/Adjuvant Additional NACT additional NACT* guidelines) cycle for cycles Therapies, n (%) N= 26 "ER low permitted No pCR: Adjuvant therapy per investigator choice Alkylating agent 5 (10%) "none with anthracycline-containing regimens BREAST BREAST CANCER Anthracycline 5 (10%) No RD suspected CANCER Capecitabine 11 (22%) 2026 Week 12 Imaging Additional NACT Olaparib 1 (2%) RD suspected Research Biopsy per investigator Surgery choice Platinum 49 (98%) Taxane 49 (98%) CMF 1 (2) 2025 ASCO #ASCO25 PRESENTED BY R. Abeiman Phase study of response- guided SG and Pembrolizumab: NeoS1 A2 ASCO CANCER Tumors with pCR post SG/P are enriched Tumor mutation burden is associated with residual disease for a homologous recombination deficiency signature post SG/P + ANACT Whole- exome sequencing Whole-exome sequencing of pre-operative tumor biopsies of pre-operative tumor biopsies 104 Mutational Signature 5G Response - Signature R NR no pathological confirmation of RD R BREAST Total Mutation counts NR no pathological confirmation of RD BREAST p=0.009 CANCER CANCER BRCAZ ATR 103 PIK381 HAWAII No 20 samples Received ANACT
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Profiling TILs in Breast CancerKaren Anderson

Dr. Karen Anderson @MayoClinic discussed lessons from TIL in breast cancer: high baseline TILs (≥50%) predicted higher pCR in both TNBC (70% vs 35%) and HER2+ (60% vs 30%). LightningSeq enables rapid TCR/BCR/HLA profiling to further probe immune biomarkers. #DAVABreast

2026 Kona Breast Cancer Summit slide — Karen Anderson, Profiling TILs in Breast Cancer
[Slide 1] Slide image analysis and computational TIL Predictive Value of Tumor Infiltrating Lymphocytes (pCR) assessments TNBC (High TILs >50%) 70% 11 - TNBC (Low TILs <50%) 35% HER2+ (High TILs >50%) 60% BREAST BREAST CANCER CANCER HER2+ (Low TILs <50%) 30% Clinical Impact: Tumors with high baseline TILs demonstrate significantly higher Pathological Complete Response (pCR) rates when treated with neoadjuvant chemotherapy, highlighting TILs as a crucial predictive biomarker. Sun et at eBiomedicine 2021, TNBC Lightning Seq: High-throughput Bulk Sequencing of BCR, TCR, and HLA TCR repertoires are reproducible and dynamic Targeted PCR and Long Read Bioinformatics Multiplexing Sequencing ADVANTAGES: Adoptive T cell profiling TCR-based replicates Identifying antigen-specific responses 8 hrs 24-48 hrs >4 hrs Turnaround Time Cost Base calling Input RNA Demultiplex Benchtop Read QC XX TCR and HLA BREAST assignment DISADVANTAGES: CANCER BREAST 6.5-11 hrs 6-10 hrs 2-4 hrs CANCER Not paired seq Custom DNA/RNA purification Lightning Seq software & Target antigens HLA and TCR PCR, barcoding, and prep Real-time Data Processing unknown
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Tailoring adjuvant chemotherapy in early stage TNBC based on TIL levelsRoberto Leon-Ferre

Higher TILs were associated with greater pCRand improved iDFS/OS in early TNBC. @rleonferre from @MayoClinic highlighted that stage I TNBC with TILs ≥50% had 5-year RFS, DRFS, and OS ≥90% without chemotherapy, informing the TIL-CHOICE de-escalation trial. #DAVABreast

2026 Kona Breast Cancer Summit slide — Roberto Leon-Ferre, Tailoring adjuvant chemotherapy in early stage TNBC based on TIL levels
[Slide 1] TILs = higher pCR with neoadjuvant chemo +/- ICI TILs = iDFS, DDFS and OS with adjuvant chemo GBG trials (chemo only) NeoPACT (neoadjuvant docetaxel, carbo & pembro) 100% 1.00 80% in D-DFS (probability) 0.75 76% For reference: 60% 0.50 KN-522 pCR rate was 63% 40% and TILE 30% 20 41% - - 0.25 and and BREAST 20% 10 BREAST - 1 CANCER 0% CANCER - 230% <30% - 0 2 3 4 5 6 7 8 9 10 sTILs a Time Since Random Assignment (years) 82% ≥T2, 39% N+, 46% PD-L1+ Biomarkers for tailoring systemic therapy: TILs TIL-rich stage I TNBC may have favorable outcomes without chemotherapy TIL-CHOICE: TIL-Guided Chemotherapy in Stage 1 TNBC Observation . Cohort A Each 10% TIL increment SURGERY pTac, pNo Patient choice' adjuvant I (TILS 275X) for 10% improvement in RFS Adjuvant chemo 13% improvement in DRFS TPC NCCN guidelines) 12% reduction in the risk of death Eligibility Cohort . TMK beery) ) Cohort TAT days SQ Pembro cycles - - vis Est : EXE Chemo cycles' Cohort # SURGERY pCR Observation BREAST TILS RFS 05 Ongoing trials using TILs in stage TNBC BREAST (TILs <75%) LIP No pCR Adjuvant TPC CANCER All 1081 (100%) 77% 82% [80-84] Stage TNBC & CANCER Chemo cycles' TPC for patients [75-79] 85% [83-87] pre TILs >50% had OPTImaL: Netherlands, PI Kok 6 2026 : <30 726 (67%) 73% [70-76] 78% [75-80] [79-84] I Stage 5y RFS, DRFS ETNA: France/Spain, Tumor or cm >30 352 (33%) 85% 87-92] 9 and os >90% Pls: Rassy, Pistilli, Oliveira (n=1081)1 TIL-CHOICE: US, Alliance/ECOG, >50 225 (21%) 90% [91-96] without chemo Pls: Leon-Ferre Klar >75 108 (10%) 92% Study Chair: Roberto Leon-Ferre, MD, Mayo Clinic (Alliance) Study Co-Chair: Natalie Klar, MD, NYU Langone (ECOG-ACRIN) ALLIANCE
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PREDICT-RD: ctDNA surveillance in TNBC with residual diseaseYara Abdou

@YAbdouMD from @UNC presented PREDICT-RD (TBCRC-071): a prospective ctDNA surveillance study in stage II/III TNBC with residual disease (RCB II/III) post-NAT. ctDNA+ patients receive adjuvant Dato-DXd x8 cycles for MRD-only disease before overt recurrence. #DAVABreast

PREDICT-RDTBCRC-071
2026 Kona Breast Cancer Summit slide — Yara Abdou, PREDICT-RD: ctDNA surveillance in TNBC with residual disease
[Slide 1] ctDNA Detection of MRD Predicts Recurrence Rationale A ctDNA-based MRD detection predicts recurrence Event-Free Survival as a Function of RCB in with high sensitivity and specificity patients) Current SOC in stage II/III TNBC: TNBC post NACT neoadjuvant chemotherapy + . pembrolizumab, followed by ctDNA+ status predicts inferior 3-year EFS among adjuvant systemic therapy + RT RCB-II patients (65% vs. 87%, P = 0.044) and RCB- Time (years) III patients (13% vs. 40%, = 0.081) Despite treatment advances, patients with residual disease after BREAST BREAST CANCER therapy, particularly patients with CANCER Detecting MRD is a promising approach to higher residual cancer burden (RCB 2026 * identifying patients at high risk of recurrence after II/III), remain at high risk of recurrence (~35-50%) mostly within is definitive therapy, who may benefit from treatment 12 24 26 the first 3 years after surgery escalation while disease remains curable. Time Months) (Yau et at Lancet 2022) - - - Shecklest PREDICT-RD (TBCRC-071): Study Schema PREDICT-RD (TBCRC-071): Intervention Stage H/III TNBC Adjuvant Follow-up after Prospective, single-arm study in Stage n/ml TNBC Adjuvant Follow-up after Residual disease after NAT systemic therapy treatment which we will enroll 78 patients with Residual disease after NAT systemic therapy treatment RCB 11/111 +/-RT (36 months) stage H/III TNBC and residual RCB H/III +/-RT (36 months) disease (RCB II/III) at the time of Patients with MRD-only disease . Blood draws to Blood draws to surgery, after neoadjuvant therapy. . Blood draws to Blood draws to will then enroll in the therapeutic ctDNA test: Signatera Genome assess ctDNA assess ctDNA assess ctDNA assess ctDNA part of the study, which entails Patients undergo serial ctDNA ctDNA test: Signatera Genome every weeks every 12 weeks every weeks every weeks adjuvant Dato-DXd for eight monitoring after surgery. cycles (6 months) BREAST ctDNA positive BREAST ctDNA positive CANCER CANCER SOC workup Treatment with Dato DXd SOC workup Scan for metastasis Follow up after Scan for metastasis OFF study metastasis No X8 cycles (6 months)* treatment OFF study metastasis metastasis NCT07069595 NCT07069595 PI: Yara Abdou PI: Yara Abdou Blood draws to Blood draws to assess tDNA assess ctDNA every weeks every 12 weeks at any point after two cycles of planned adjuvant therapy or up until two years of follow up
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Surgical Advances

Moderator · Laura Esserman
PM4 of 4 with slides

Coming up: a focused session on surgical advances in breast cancer care. Moderated by Laura Esserman, MD, this expert-led discussion will highlight evolving surgical approaches, innovation, and key considerations shaping contemporary practice. Stay tuned! #DAVABreast

2026 Kona Breast Cancer Summit — Surgical Advances session
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Panel on advances in breast surgery #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Surgical Advances session
[Slide 1] & & D DAVAONCOLOGY ...facilitating successful drug development ...facilit ...facilitating successful drug development .......... ......... D & D KONA ......... .......... BREAST CANCER SUMMIT in DAVA On & ......... D & 4TR SUMMIT ON BREAST CANCER 2026 DAVAOncology HAWAII BREAST CANCER MODERATOR DAVAOncology ...facilitating DAVAOncology successful drug developmer DAAOnolog ...facilitating successful drug development Oncology AVAOncok AOA DAVAOncology™ DAVAOncology DAVAOncology DAVAOncology DAVAOncology™ DAVAC DAVAOrcology™ DAVAOncology® DAVAOncology™ DAVAOncology
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Using biopsy to assess pCR status and avoid surgical resectionHenry Kuerer

A pivotal trial eliminating breast surgery in exceptional responders to NST was presented by @HenryKuerer from @UTMDAnderson: image-guided VACB confirmed no residual disease, and at 5-year follow-up patients had 100% IBTR-free survival and 100% OS/DFS. #DAVABreast

2026 Kona Breast Cancer Summit slide — Henry Kuerer, Using biopsy to assess pCR status and avoid surgical resection
[Slide 1] Kaplan-Meier / survival curve — table and text data only
Pivotal multicenter trial for eliminating breast cancer surgery in exceptional Multicenter trial 2016-0046: Eliminating Breast Cancer Surgery in responders to neoadjuvant systemic therapy NCT02945579 Exceptional Responders With Neoadjuvant Systemic Therapy MD Anderson Cancer Network, UPMC, Mayo Clinic, and Levine Cancer Institute Super Selective Inclusion Criteria Exclusion Criteria Women age ≥40 Prior ipsilateral breast cancer Cohort A1 N = 50 50% HER2+, 50% TN Unicentric TN or HER2+ invasive â 5 cm, Current pregnancy Follow NO/N1 (≤ 4 abnormal axillary nodes on T4/T3 disease rCR/rPR every no No residual initial ultrasound with biopsy if suspicious) disease No Breast Surgery Primary endpoint Clinical progression >20% in the Image-guided (invasive and situ) IBTR free survival BREAST Receiving any clinical chosen NST BREAST HER2+/TN breast or new evidence of nodal biopsy CANCER CANCER Neoadjuvant Tumor must shrink <= 2 cm final breast metastases 12 9G VACB Secondary endpoints systemic Residual Standard Need for bx on f/u HAWAII therapy disease Surgery QoL/Cosmesis imaging Distant metastases invasive and situ) Correlate CTC Lesion must be <2 cm and cDNA after NST clip placed OS/DFS Kuerer HM et al; Lancet Oncology 2022; JAMA ONC 2025 Kuerer et al, Lancet Oncol 2022; JAMA Oncology 2025 RESULTS: Primary outcome IBTR-free survival among patients who did not undergo breast surgery 5-year planned analysis Summary and Conclusions In this first trial in the field, we eliminated breast surgery with careful selection of 100% IBTRFS Probability ipsilateral recurrence free survival patients and rigorous image-guided biopsy to assess pCR after NST Secondary 100% OS/DFS This new treatment approach appears safe and effective as there have been no recurrences at 5-years BREAST BREAST CANCER CANCER Further clinical trials - - already underway- will continue to validate this initial study No Risk Time (months) Korean OPTIMIST & Japanese JCOG 1806 HAWAI SABCS 2026 We owe it to our patients to do these future studies precisely as we outlined to achieve the initial excellent results and set a new-standard Median follow-up 5-years (IQR 4-6 years); Kuerer et al. JAMA Oncology 2025
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The case for not doing contralateral mastectomiesFred Dirbas

New data presented by Frederick M. Dirbas, MD from @StanfordMed :bilateral mastectomy ↓ contralateral cancer 8-fold (97 vs 728–766/36,028) but 20-yr breast cancer mortality unchanged (8.5% vs 9.1% vs 8.5%). Complication RR up to 1.73 with bilateral reconstruction. Frederick M. Dirbas, MD from @StanfordMed #DAVABreast

2026 Kona Breast Cancer Summit slide — Fred Dirbas, The case for not doing contralateral mastectomies
[Slide 1] The operation does exactly what we promise Fifty years of de-escalation Contralateral breast cancers over 20 years, per 36,028 women 766 Mastectomy rate, stage I-III 728 47.6% 42.3% 31.6% 33.3% BREAST 97 CANCER CPM among mastectomy patients Lumpectomy Unilateral Bilateral BREAST CANCER mastectomy mastectomy 2010 2023 Three matched cohorts, 20 years in SEER. An eightfold reduction — unambiguous. Giannakeas V. Lim DW, Narod SA. JAMA Oncol. 2024; 1228-1236 Every other de-escalation happened on randomised evidence. CPM is the only one never Stanford tested in a trial - and the only one moving the other way. MEDICINE Surgery Evolution of breast concer treatment 2010-2023 Ann Surg Oncol. 2026. doi: 11245/s10434-025-19065-2 / NCDB, 1,769,438 patients. Both trends P.S 0.001. Stanford Surgery MEDICINE And it does not do the thing they came for A contralateral cancer is a bad prognostic event Hazard of breast cancer death after CBC Penalty concentrated early Breast cancer mortality at 20 years SEER. Giannakeas 2024 4.00 California registry, age 15-39 2.73 2.01 8.5% 9.1% 8.5% Danish nationwide cohort 2.48 1.36 Swedish cohort, CBC 5 yr 2.30 California registry, age 40-64 2.13 0.37 California registry. age 2 65 1.52 no excess risk 1.5 yr yr 8 yr Interval to CBC BREAST BREAST CANCER CANCER Lumpectomy Unilateral Bilateral Contralateral tumours are found earlier and at lower stage — yet survival is worse. mastectomy mastectomy 5-15% are clonal metastases from the index tumour, not new primaries, not defined by receptor status Same women. Same twenty years. Preventing the second cancer changed nothing. The dangerous ones were never preventable. Giannakeas V, Lim DW, Nared SA JAMA Oncol 2024; 1228-1236 California Cancer Registry 2023 / Donish cohort 2018 / Kim H, JAMA Netw Open 2023 / Klevebring 2015 Stanford Surgery MEDICINE Stanford MEDICINE Surgery
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Insights into the newly approved robotic mastectomyNimmi Kapoor

RCT data comparing robotic vs open nipple-sparing mastectomy was highlighted by @DrNimmiKapoorfrom @dgsomucla: operative time 141.6 vs 83.9 min, SAEs in 3 vs 8 patients, and no device-related SAEs with rNSM. #DAVABreast

2026 Kona Breast Cancer Summit slide — Nimmi Kapoor, Insights into the newly approved robotic mastectomy
[Slide 1] 00 Fig. 3. Oncological procedure. (A) A 35-mm longitudinal skin incision on the mid-axillary line. (B) An access port of the da Vinci SP surgical system placed on the skin incision. (C) Dissection of the breast tissue from major pectoral muscle. (D) Surgical margin of the nipple examined intraoperatively. (E) Dissection of the breast tissue from skin. 00 a 00 . (F) Resected breast tissue via the 35-mm skin incision. & of D 00 R BREAST BREAST CANCER CANCER & & inframammary nipple sparing mastectomy technique (A) Preoperative positioning and marking inframammary folds: (B) inframammary incision; (C) everting skin edges and beginning Bap dissection (D) flap dissection above the mipple with fiberoptic retractor (E) dissection of breast off pectoralis Br. breast tissue; Mj. major pectoral muscle N. nipple muscle axillary breast tail (G) (H) a a 74 patients completed surgery, totaling 65 rNSM and 66 open NSM a 00 B 00 Operative time was longer for rNSM (141.6 versus 83.9 min) 00 No conversions to open Serious adverse events (SAEs) occurred in three 00 Results rNSM and eight open NSM patients, with no device-related SAEs NAC preservation was 100% for rNSM and 98.5% BREAST BREAST for open NSM. CANCER CANCER Identical positive margin rates (six patients in & 8 each) Higher BREAST-Q scores favored rNSM in Fig. 2 Single port placement Fig. 3 Robotic docking with access platform in situ multiple domains.
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Using fluorescent imaging to optimize surgical lumpectomy resectionsIrene Wapnir

Data reported by @wapnir from @StanfordMed shows that pFGS removed tumor left behind after lumpectomy in 27/357 patients; 82% of these had corresponding negative lumpectomy margins, highlighting occult residual disease. #DAVABreast

2026 Kona Breast Cancer Summit slide — Irene Wapnir, Using fluorescent imaging to optimize surgical lumpectomy resections
[Slide 1] Margin Sampling Peglucianine Fluorescent Guided Surgery (pFGS) of the Lumpectomy Cavity Pathologists' assessment of margins is LIMITED Ex-vivo Tumor Cavity a b c d 20% Re-excision lumpectomies for involved margins Majority are FALSE positive PFG-guided Margin Evaluation BREAST Residual cancer in < 40% re- BREAST CANCER 5 micron CANCER excisions 3- 4 mm section IV injection 2-6 hours section prior to surgery SURGERY Per Lumpectomy Cavity Margin Results Per Patient Analysis : Removal of Residual Cancer 46% patients had at least one 10% (35/357) of patients benefitted shaved margin taken N=9 Total of 371 fluorescent margins N=269 7.6% (27/357) pFGS removed tumor left behind after lumpectomy 34 (9.2%) residual cancer 22/27 (82%) from corresponding lumpectomy negative margins 8.5% 15% (9/62) with positive lumpectomy margins converted to negative 11.7% Positive Lump Margin Negative Lump Margin positive positive spared second surgeries BREAST CANCER BREAST CANCER 10 CC average pFGS margin volume resected 2026 N=68 N=25 No differences BREAST-Q breast appearance PROMS between patients +/- pFGS margins taken
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Younger Populations

Moderator · Jordan Jackson
PM3 of 4 with slides

Many women still find their own breast cancers. Victoria Seewald, MD @cityofhope notes 46–47% self-detection and proposes a modified BSE focused less on technique and more on prompt communication and evaluation. #DAVABreast

2026 Kona Breast Cancer Summit — Younger Populations session
[Slide 1] Yes, women find their own breast cancers Interval cancers - need for reporting between screening JOURNAL OF WOMEN'S HEALTH Volume 20, Number 2011 Original Articles Normal Invasive CA Metastasis Mary DOI: Time 0 mos 12 mos Self-Detection Remains a Key Method of Breast Cancer Detection for U.S. Women Normal Invasive CA Metastasis Mara Roth M.D. Joann G. Elmore, M.D. M.P.H. Joyce Yi-Frazier Ph.D.) Lisa M Reisch, Ph.D. Natalia V. Oster M.P.H.) and Diana L Miglioretti, Ph.D.² 0 mos 12 mos Methods: National Health Interview Survey, 361 women survivors diagnosed with breast cancer between 1980 and 2003. Focused qualitative interviews Durham, NC - informal BREAST CANCER Query: How was your breast cancer found? BREAST - 121 women; 51 cancer, 70 no cancer: CANCER Results: Most women survivors (57%) reported a detection method other than "I found a cancer, but no one would listen to me" mammographic examination: most common BSE (25%) or by accident (18%). "Don't have insurance - — afraid of bankruptcy" Conclusions: A large percentage of breast cancers are detected by women "I am too young for mammograms" Modified breast self examination . Takeaways OR give your breast a "high-five" Ribs Chest Wall - Many women find their own breast cancers - 46-57% - Use flat hand, not fingertips Pectoralis - Perhaps modified BSE? - Move breast around muscle Put your bra on, shower, live Ducts Less about technique - more about communication I - Report any lump — no matter how you Nipple - Shanghai study needs to be repeated in US. found it - Call us, text us, email us - we are there BREAST CANCER - We will US in 48 business hours Areola BREAST CANCER Acknowledgements: Funding: - You are not wasting the breast Collecting duct Stephanie Robertson Triangle Susan G. Komen community radiologist's time - no cancer makes Adipose tissue Nora Talbert, M.D. Friends you can count on them happy Adrian Ambrose, M.D. NIH/NCI U54 CA285116 Anne Ford, M.D. NIH/NCI T32 CA221709
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Coming up: a timely session focused on breast cancer in younger populations. Moderated by @HenryKuerer this expert-led discussion will explore unique clinical considerations, emerging challenges, and evolving strategies for younger patients. Stay tuned! #DAVABreast

2026 Kona Breast Cancer Summit — Younger Populations session
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Postpartum breast cancer decision-making with high-risk geneticsVictoria Seewaldt
Targeting increased immune activation in postpartum TNBCNimmi Kapoor

In a multicenterTNBC cohort treated with NAC+IO presented by @DrNimmiKapoor from @dgsomucla, pCR was 76% in women <5 years postpartum vs 66% in nulliparous women; historical young-women NAC-alone pCR was 51%. #DAVABreast

2026 Kona Breast Cancer Summit slide — Nimmi Kapoor, Targeting increased immune activation in postpartum TNBC
[Slide 1] Scope of the Issue JAMA Network Open. 2022 Original investigation Oncology There are more than Breast cancer 6 million Childbearing is more Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah commonly delayed incidence in young pregnancies per year women is increasing Zhenzhen Durg, PIO MPH Solange Bassale MS Serial indial MD. MBA Fraser MSPH Emily Guints, MS. Weston Anderson, SA Motorns PhD MBA in the United States Smith PhD, Pepper PhD - Breast cancer is the leading cause of Up to 50% of YWBC SEER 2,970 women <45 W breast cancer death in women is PPBC ages 20-49 Compared to nulliparous women, those within 5 years of childbirth were associated with: Stal . Stel JAMA EAST Network Open. BREAST Higher rate of distant metastatis 2024 NCER CANCER Original Investigation Public Health Higher rate of breast cancer death Breast Cancer Incidence Among US Women Aged 20 to 49 Years by Race, Stage, and Hormone Receptor Status Sara Murtagh MD fe . Clinical Data: Evaluating pCR in TNBC by Postpartum Status In a multi-center cohort of patients Conclusions pCR rates for TNBC in YWBC W TNBC treated W NAC-IO YWBC rates are increasing, possibly related to delayed 80% pCR was higher in women within 5 childbearing years of childbirth compared to 70% nulliparous women PPBC has an immune rich landscape 60% Clinical findings suggest an improved response to NAC-IO Data unpublished, for SABCS... 50% in PPBC with TNBC 76% 40% Laboratory findings point to prediction response with IO in 66% 51% N-42 EAST 30% N=79 BREAST PPBC in both TNBC and other subtypes NCER CANCER 20% Catart 10% Future studies are needed! YWBC NAC alone Nulliparous NAC+IO (pCR)
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Sexuality and quality of life on aromatase inhibitorsOana Danciu

AI-induced low sexual desire may affect up to 83% of breast cancer survivors receiving AI therapy. Oana C. Danciu, MD from @UICancerCenter, highlights a study testing bupropion as a potential intervention. #DAVABreast

2026 Kona Breast Cancer Summit slide — Oana Danciu, Sexuality and quality of life on aromatase inhibitors
[Slide 1] UI Health Health Background LLINOS Rationale CENTER CANCER CENTER . - Non-adherence to AI therapy is high (20-50%) and strongly correlated with poor survival outcome Al-induced low sexual desire Recognized condition in DSM-IV Bupropion is an aminoketone antidepressant approved for major depressive Measurable using standardized questionnaires such as the Female Sexual Functioning disorder and seasonal affective disorder Index (FSFI) BREAST Prevalence of Al-induced low sexual desire in BC survivors : 83% (3x more among BREAST CANCER CANCER patients receiving AI therapy) Bupropion shown efficacy in pre- and post-menopausal healthy women when it was studied as a repurposed agent; not studied in women on AI therapy Treatment is not well defined with several interventions tried in non-cancer patients Kidwell 2014 Treatment 2011 M Al-Associated Low Sexual Desire Study Schema (n=100) 2-year enrollment and 3-year follow-up UI Health Al-associest ins Low Sexual Desire Index CANCER CENTER Desire Doman Score 8 therapy - Early the Cancer Two questions focused on sexual desire Over the past 4 weeks, how often do you feel sexual desire or interest Change Change class Almost always or always dels) Most times - - option I 1 Sometimes Doman Soore Cesis Commin Score A few times Denect Soone -- Soure Crem Score - Almost never or never - license Over the past 4 weeks how would you rate your level (degree) of sexual desire or interest BREAST Deces - Casis Score BREAST Very high CANCER CANCER I Service years High option i / FSR Gestel Comen Score - Domain Soore - . Moderate Low - (Peans) survice - very low or none - - - Desire Somets Soaring ulated FSFI Desire Domain Score (question 1 score + question 2 score) X 0.6. Range 1.2-6 I care Score <5 = low sexual desire - : hown safety other -
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Elinzanetant/fezolinetant to improve hot flashesMilana Dolezal

Hot flashes can affect more than comfort-up to 40% of patients discontinue endocrine therapy. Milana V. Dolezal, MD from @StanfordMed highlights VMS management as an important component of breast cancer survivorship and treatment adherence. #DAVABreast

2026 Kona Breast Cancer Summit slide — Milana Dolezal, Elinzanetant/fezolinetant to improve hot flashes
[Slide 1] Breast cancer recurrence isn't the only clinically meaningful How can we HELP VMS Abrupt menopause/SUFFERING endpoint (in pre/post menopausal)-Abrupt Compliance KNDy Neurons menopause/SUFFERING Meds Compliance Kisspeptin/Neurokinin B/Dynorphin EMERGING HYPOTHESIS RELATED TO DISCOVERY THAT ESTROGEN-SENSITIVE KNDY NEURONS PROJECTING White TO THE THERMOREGULAT CENTER ALSO REGULATE HYPOTHALAMIC GNRH Black Hypothalamus Hot flashes Preclinical studies demonstrated the role of KNDy Thermoregulatory Center neurons in thermoregulation Up to 40% of patients Efferent neural pathways controlling discontinue MP( defense effectors KNDy neurons are kisspeptin-neurokinin B-dynorphin ET(endocrine containing cells in the hypothalamus Cold sweats therapy) GnRH Vasodiation KNDy neurons project to GnRH nerve terminals and to (Murphy et al Breast the TRC Cancer Res Treat 2012 BREAST Night sweats and Bright JCO 2023, BREAST Signals from skin LH stimulates ovarian estrogen secretion Xin Hu CANCER thermoreoeptors Estrogen CANCER negative Estrogen negative feedback reduces serum LH and THRIVE trial in Black feedback va CARD 0.0 1.0 2.0 3.0 women JNCCN 2025 NK.R neurokinin B and kisspeptin mRNA in KNDy neurons 0.5 1.5 2.5 3.5 4.0 LH (>50% stop ET early) The TRC receives signals from skin thermoreceptors Symptom Severity Score Ovary and then sends signals to modulate heat dissipation AP anternor pitulary ERa. estragen receptor sipha GnRH releasing homene KNDy B-eynerphin LH hormone MnPO - mRNA massenger recorded acid NK3R neurosinn receptor DC aptic chasm TRC, hermoregulatory center SOFT/TEXT Francis PA NEJM 2018 379(2): 122 Murphy et at Breast Cancer Res Treat 2012 Bright JCO 2023, Xin Hu: THRIVE trial in Black women UNCCN 2025 2013;34(3):211-227. EARLY BREAST CANCER (EBC) Hormone receptor (HR)+ HOT FLASHES EARLY BREAST CANCER (EBC) Hormone receptor (HR)+ HOT FLASHES Management with Elinzanetant (a dual neurokinin-targeted therapy NK-1/3 Management with Elinzanetant (a dual neurokinin-targeted therapy NK-1/3 Receptor antagonist) Receptor antagonist) Methods Trial design Results - Mean change from baseline in average daily moderate-to-severe VMS frequency over time OASIS-4 (NCT05587295) multicenter randomized blind placebo-controlied Phase II tial evaluating elinzanetant 120mg for the treatment of VMS associated with ET in women with or high risk of HR+ breast cancer Key Take Aways: Placebo-controlled period Elinzanetant period (blinded) - Elinzanetant significantly reduced . Week FOLLOW amount and severity of Hot flashes/ 2 4 6 8 10 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 SCREENING UP Vasomotor symptoms(VMS) over 0.00 ELINZANETANT ELINZANETANT placebo in women receiving anti- Elinzanetant 120 mg Placebo n=758 estrogen therapy (ET) for Hormone NAMED PLACEBO ELINZANETANT ELINZANETANT receptor (HR+) Breast cancer Results seen w/in 1 mo w/VMS 474 enrolled reduction BREAST pts Supportive quality of life BREAST (95% CI) Limitations; No Ribo CDK CANCER 12 WEEKS 40 WEEKS OPTIONAL 4 WEEKS CANCER DDI/LFT's 2-YEAR improvement and potentially improve Mean change from baseline average daily frequency of VMS EXTENSION ET compliance Stable on ET therapy SAFETY: same as women with natural or surgically induced ASCO ASCO menopause (OASIS 1-3) Switch to elinzanetant - 2025 ASCO #ASCO25 Fatima ASCO
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8 sessions · 46 talks

Thu, Aug 20, 2026

Obesity and Metabolism in Breast Cancer

Moderator · Joyce O'Shaughnessy
AM5 of 7 with slides

Starting Soon: Obesity and Metabolism in Breast Cancer Moderated by @BCJoyceO @TexasOncology #DAVABreast

2026 Kona Breast Cancer Summit — Obesity and Metabolism in Breast Cancer session
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Starting Day 2 with a Panel on obesity and metabolism in breast cancer #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Obesity and Metabolism in Breast Cancer session
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Impact of GLP-1 agonists on therapeutic response in TNBCJoshua Gruber

Can GLP-1R agonists affect response in TNBC? @joshuagruber @StanfordMed linked GLP1Ra/DPP4i use with worse outcomes, GLP1R expression, and survival signaling. Avoidance during neoadjuvant chemoimmunotherapy may be prudent pending confirmation. #DAVABreast

2026 Kona Breast Cancer Summit slide — Joshua Gruber, Impact of GLP-1 agonists on therapeutic response in TNBC2026 Kona Breast Cancer Summit slide — Joshua Gruber, Impact of GLP-1 agonists on therapeutic response in TNBC2026 Kona Breast Cancer Summit slide — Joshua Gruber, Impact of GLP-1 agonists on therapeutic response in TNBC2026 Kona Breast Cancer Summit slide — Joshua Gruber, Impact of GLP-1 agonists on therapeutic response in TNBC
[Slide 1] What happens if a patient takes GLP1Ra (Ozempic, etc.) during Chemoimmunotherapy for TNBC? KN522 Neo-adj. Adjuvant Phase Cycles 1-4 (12 wk) Cycles 5-8(12 wk) Cycles 1-9(27 wk) Carboplatin Doxorubicin Paclitaxel Cyclophosphamide SURGERY Pembrolizumab 200 mg Q3W BREAST Pembrolizumab 200 mg Q3W CANCER 2026 PARAII Pathologic complete response (pCR) rate +/- GLP1Ra UT Southwestern Medical Center --- [Slide 2] . GLP1-RA/DPP4i usage confers worse outcomes . A 100 . 80 Non-GLP1 Drugs (N=46) BREAST Pathologic Complete Response (pCR) Rate (%) GLP1 Drugs (N=26) 63.0 65.0 Non-Diabetic (N=271) 60 40 30.8 CANCER 20 2026 HAWAI 0 Non-GLP1 Drugs GLP1 Drugs Non-Diabetic --- [Slide 3] GLP-1 drugs suppress cytokine secretion from tumor cells Four panels, each plotting cytokine concentration (pg/mL) against semaglutide concentration (0, 5, 10 micromolar): - CCL2/MCP-1 - y-axis 0 to 1000 pg/mL - IL-6 - y-axis 0 to 2.5 pg/mL - VEGF-A - y-axis 0 to 4x10^4 pg/mL - IL-10 - y-axis 0 to 6 pg/mL Each panel marks **** significance for 5 and 10 micromolar semaglutide versus untreated. Source: UT Southwestern Medical Center. Preclinical (tumor-cell) data - not a clinical endpoint. Bar values are not transcribed: they are legible only from the chart itself. --- [Slide 4] GLP1R expression may explain the paradoxical effects on cancer outcomes GLP1 GLP1R GLP1 ? - + 1 cytokines tumor cell macrophage 026 AWAB Conclusions: 1. Avoidance or discontinuation of GLP1 Ra drugs during neoadjuvant chemoimmunotherapy for TNBC may be prudent, pending confirmatory studies. 2. ER+ breast cancers are devoid of GLP1R (GLP1 drugs may be ok)
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Weight management and obesity treatment to combat inflammationJenni Sheng

Weight management matters in breast cancer survivorship. Jenni Sheng, MD at @HopkinsMedicine: ≥5% weight loss improved physical function and reduced pain, better sleep supported behavioral weight loss, and pharmacotherapy augmented lifestyle interventions. #DAVABreast

2026 Kona Breast Cancer Summit slide — Jenni Sheng, Weight management and obesity treatment to combat inflammation2026 Kona Breast Cancer Summit slide — Jenni Sheng, Weight management and obesity treatment to combat inflammation2026 Kona Breast Cancer Summit slide — Jenni Sheng, Weight management and obesity treatment to combat inflammation2026 Kona Breast Cancer Summit slide — Jenni Sheng, Weight management and obesity treatment to combat inflammation
[Slide 1] Nearly 15% shift to a higher BMI category Shifts in BMI Classification WHO/CDC BMI Category BMI (kg/m2) Increase, Overweight to Obese, Normal/Healthy weight 18.5- 24.9 11.4% Overweight 25.0- 29.9 11% 2.90% Increase, Normal/Underweight Obesity Class (Mild) 30.0- 34.9 to Overweight, 2.9% Obesity Class II (Moderate) 35.0- 39.9 30.70% Decrease, Overweight to 5.70% 1.40% Normal/Underweight, 5.7% Obesity Class III (Severe) >40.0 1.40% Decrease, Obese to Normal/Underweight, 1.4% We observed a significant >5% increase Decrease, Obese to in BMI from diagnosis to most recent Overweight, 1.4% follow-up (p = 0.009), particularly Stayed within among those who were overweight at 25.70% ST Normal/Underweight, 25.7% diagnosis (p = 0.003). ER 20.70% Stayed within Overweight, 20.70% 2026 HAWAI Stayed within Obese, 30.70% Goyal et al. Current Oncology 2022 JOHNS HOPKINS THE SIDNEY KIMMEL MEDICINE COMPREHENSIVE CANCER CENTER --- [Slide 2] Better baseline sleep is associated with weight loss --------- Patient Characteristics based on randomization and sleep group POWER-remote Self-Directed Total Poor sleep Better sleep Poor sleep Better sleep Sample Size N = 94 N = 16 N 32 N 12 N 34 Baseline Weight 189.0 202.1 (32.3) 182.6 (27.7) 186.4 (26.2) 189.5 (25.6) Mean (SD) (28.0) % weight chg. from BL to -3.3 (5.7) -4.1 -6.8 -0.9 -0.6 (4.2) BREAST 6mo - Mean (SD) (4.8) (6.5) (2.8) CANCER % weight chg. from BL to -3.5 (7.4) -3.9 -7.5 -1.4 -0.0 (6.1) 2026 Annual 12mo Mean (SD) (7.3) (7.9) (4.3) Sheng et al. Obesity 2025. --- [Slide 3] Cancer, Obesity/Overweight and Insomnia (COIN) 8 weeks 6 months Sleep education alone 30 participants Key eligibility: na POWER-based lifestyle Stage O-III, RANDOMIZE intervention BMI>25, insomnia disorder Cognitive Behavioral Intervention for Insomnia BREAST (CBT-I) CANCER 2026 HAWAII Primary objective: To compare the effects of CBT-I+BWL and EDU+BWL on % weight loss at 3 and 6 months Collaboration with Janelle Coughlin PhD (Associate Director of Center for Behavior and Health) --- [Slide 4] Waterfall plot of weight change at 6 months (n=47) 5 S Nearly three quarters 0 . (72%) of participants were in the SLOW- Change from baseline (%) -5 BWL arm. -10 Of 38 in the SLOW- 4TH SUMMIT ON BWL, approximately REAST CANCER -15 42% attained at least 2026 Study Arm 5% weight loss. HAWAII BREAST CANCER SLOW-BWL FAST-BWL -20 Sheng et al. Clinical Cancer Research. 2026.
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Obesity and HR+ breast cancer: the metabolic-disarray axisCoral Omene

Obesity may shape HR+/HER2− breast cancer through hyperestrogenism, insulin resistance, adipokine dysregulation, inflammation, and immune dysfunction. @Omene_CO @RutgersCancer highlighted FITWISE testing tirzepatide in adjuvant HR+/HER2− BC. #DAVABreast

2026 Kona Breast Cancer Summit slide — Coral Omene, Obesity and HR+ breast cancer: the metabolic-disarray axis2026 Kona Breast Cancer Summit slide — Coral Omene, Obesity and HR+ breast cancer: the metabolic-disarray axis2026 Kona Breast Cancer Summit slide — Coral Omene, Obesity and HR+ breast cancer: the metabolic-disarray axis2026 Kona Breast Cancer Summit slide — Coral Omene, Obesity and HR+ breast cancer: the metabolic-disarray axis
[Slide 1] Obesity and HR+/HER2- Breast Cancer: The Metabolic- Disarray Axis in Early and Metastatic Disease Hormonal/Adipokine Dysregulation 1 Leptin - promotes tumor cell Metabolic Dysregulation proliferation & migration Insulin resistance compensatory Adiponectin (anti-proliferative) loss of hyperinsulinemia tumor suppression 1 7. GF-1R pathway drives Adipokines AMPK INTOR Leptin adiponectin ratio correlates with BC PI3K/AKT/mTOR tumor signating Growth hormones dyaregulation aggressiveness Insurn Type 2 diabetes confers -20-27% - Excess adipose issue 1 aromatase BC-specific mortality activity estrogen Lipid metabolism reprogramming AMPK CDM Estrogen drives HR+ tumor proliferation supports tumor energy demands POT POLI Lipids - Promotion if inmune checkpoints FAO I Energy $ Chronic Inflammation Preas - Suppression of Adipose macrophages - TNF-a. IL-6, immunosurvellance L-18 BREAST Immune Suppression NF-4B activation furnor permissive Alters recruitment and function of immune VAT CANCER microenvironment cells, MDSCs. Macrophages Ligits Low page information Inflammatory cytokines promote Production of immunosuppressive factors TMP + angiogenesis & metastasis NK cell dysfunction - reduced cytotoxicity CRP and IL-6 independently predict BC Increased expression of immune recurrence risk checkpoints DNA damage Lydia Dyck and cycle Lynch, Cancer 2018 RW. Barnabas R Ratigers HEALTH Lancer institute - --- [Slide 2] Schema Enroll 20 Black and 20 Non-Black breast cancer patients may the 5% or more body following criteria Tirzepatide SC inj. weekly for 2 years weight reduction Have HR+/Her2 early-stage breast cancer, (Stage I-III). Safety and BMI, WHR, physical tolerability BMI of 30 kg/m2 or greater, OR a assessments every BMI of 27 kg/m2 or greater with cycle for first 6 cycles, Abdominal 3 year IDFS* one weight-related complication then every 3 cycles for adipose tissue remainder of 2 years, biopsy, QOL 3 year DRFS* Completed definitive treatment then every 6 months for questionnaires, for cure: surgery, endocrine 1st year follow-up at baseline and Correlative and therapy. chemotherapy and radiation as indicated every 6 months exploratory analysis (Necadjuvant or adjuvant). Research bloods, at for 2 years C1, C3 & C6 for first 6 Insurance - - - Eligible for adjuvant endocrine cycles, then every 3 (IDFS) therapy with an aromatase relapie thes survice (DAFS) months thereafter for inhibitor or tamoxifen remainder of 2 years EXPLORATORY: To study metabolomic pathways and immune BREAST Use of avanat suppression, COKAN motor Parg - . cell metabolism, from adipose tissues and CANCER bischosphorate use with Cometa - sloved - per treating blood during the 2-year study. physician choice 2026 HAWAII Labs: CBC, CMP, fasting insulin, fasting blood Bucose, HgbAic total cholesterol LDL. HDL. triglycerides, IGF1, estrogen, testosterone, adiponectin, leptin, CIDNA metabolomics, immune cell metabolism FITWISE RWJBarnabas R Rutgers HEALTH Cancer institute --- [Slide 3] Exploratory: Metabolic Dysregulation Profiling metabolomic and lipidomic changes during tirzepatide treatment - -- Plasma samples (C1,3,6,9,12) BREAST Adipose CANCER biopsy Liquid chromatography- 2026 (C1,6,12) MARAD Extract lipids mass spectrometry lipidomics RWJBarnabas HEALTH R Rutgers Cancer institute --- [Slide 4] Exploratory: Immune Suppression Rationale: Obesity and Immunity Lipids differentially affect immune populations while overall FAs C036 NK cells CD36 CD8 cells promoting an immunosuppressive phenotype. PPAR mTORC1 OxLDL Cholesterol Hypothesis: tirzepatide will TIM3 change immune function in PD1 obesity, possibly through direct Survival but impaired function impeired functional responses Reduced ITNY and prenzyme production Increased checkpoint expression impact on immune cell Metabolic peralysis FAs metabolism, or indirectly through Tregs cells improved metabolic changes in BREAST SREBP CD36 the body. CANCER RORYT IL-17 Immune cell function and 2026 FASN HAWAII metabolism will be explored in ex Cholesterol vivo assays these Inconclusive If I improved survival and orolineration and CDB inhibition induced metastacio RWJBarnabas HEALTH R Rutgers Cancer Institute Lydia Dyck and Lydia Lynch, Cancer Letters 2018
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Incretin mimetics for high-risk early breast cancerJoyce O'Shaughnessy

Dr. @BCJoyceO @TexasOncology reviewed retrospective data suggesting lower breast cancer incidence and improved outcomes with incretin mimetics, while the prospective TRIM-EBC trial is evaluating tirzepatide in patients with high-risk HR+/HER2− early breast cancer. #DAVABreast

2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Incretin mimetics for high-risk early breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Incretin mimetics for high-risk early breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Incretin mimetics for high-risk early breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Incretin mimetics for high-risk early breast cancer
[Slide 1] Absolute Risk Reduction (ARR) in Breast Cancer WHY GLP-1 RECEPTOR AGONISTS Within Matched Dataset (N = 30,528) MAY INFLUENCE BREAST CANCER RISK MI Purpose: To quantify the absolute reduction in the risk of breast cancer associated with prior GLP-1 receptor agonist exposure. There are several reasons to believe GLP-1 receptor agonists could influence cancer risk. REDUCE REDUCE SYSTEMIC EFFECTS ON CELLULAR Measure Estimate 95% Wald CI 1 2 IMPROVE INSULIN RESISTANCE 3 4 BODY WEIGHT AND METABOLIC DYSFUNCTION INFLAMMATION METABOLISM AND TUMOR BIOLOGY No GLP-1 Risk 2.31% (2.07%, 2.55%) With GLP-1 Risk 1.62% (1.42%, 1.82%) Body weight reduction Absolute Risk Reduction (ARR) 0.69% (0.38%, 1.01%) through bariatric surgery reduces breast cancer risk. BREAST BREAST CANCER EVIDENCE: BARIATRIC SURGERY CANCER i Women with prior GLP-1 receptor agonist exposure had an absolute reduction of 0.69% Lower risk of breast cancer improve glucose control, insulin May lower chronic inflammation, Prectinical studies suggest potential in the risk of breast cancer compared with women without exposure. 2026 RR 0.56 direct effects on cellular metabolism sensitivity, and metabolic health- an important contributor (95% CI 0.44-0.71; factors linked to lower cancer risk. to tumor development. proliferation, and tumor microenvironment Conclusion: GLP-1 receptor agonist exposure is associated with an absolute <0.00001) reduction in breast cancer risk in this matched cohort. Int Mol Sci 24:6192, 2023 IAMA 331:38, 2024 Nat Cancer 7:260-271, 2026 Science (1979) 385:258-260, 2024 McDonald E et al. ASCO 2026 . TriNetX RWE Breast Cancer Outcomes with GLP-1 RAs Ongoing Clinical Trials: GLP-1 RAs in Breast Cancer RA - cause mortality - insulin or M TriNetX 68 US EMRs 10 10 0.8 0.5 Obesity or T2DM Prospective Evidence on the Horizon 0.5 0.5 PSM breast cancer Name Insuliner methermouse prognostic factors . NCT/Trial Agent BC Subtype Setting Primary Secondary Design 0.4 3.4 Obesity Pts Endpoint Endpoint Overal T2DM Pts 0.2 0.2 Diagnosis 2006 to NCT06518837 Tirzepatide HR+/HER2- Active >5% weight loss IDFS, DRFS, changes in BMI, FITWISE Trial BC (adjuvant) adjuvant body fat distribution, 00: during treatment, Prospective 2023 metabolic markers, ctDNA; Omene, C. treatment 2 $ 6 1 feasibility metabolomic pathways and Time.y 50% black immune cell metabolism ($) 13 0 945 10-yr followup pts 214 127 105 Insula 457 227 125 14 - BREAST Primary Endpoint: BREAST NCT06517212 Tirzepatide HR+/HER2- High-risk, Metastatic CIDNA clearance, TTR, Prospective CANCER CANCER TRIM-EBC Trial high-risk BC N+ early- disease DFS, Exploratory analysis All cause mortality (O'Shaughnessy stage prevention of metabolic, hormonal and Kelly) and immune cell changes Secondary: RFS Tatum KL et al. JAMA Network OPEN 2026 . --- [Slide 2] Absolute Risk Reduction (ARR) in Breast Cancer WHY GLP-1 RECEPTOR AGONISTS Within Matched Dataset (N = 30,528) MAY INFLUENCE BREAST CANCER RISK MI Purpose: To quantify the absolute reduction in the risk of breast cancer associated with prior GLP-1 receptor agonist exposure. There are several reasons to believe GLP-1 receptor agonists could influence cancer risk. REDUCE REDUCE SYSTEMIC EFFECTS ON CELLULAR Measure Estimate 95% Wald CI 1 2 IMPROVE INSULIN RESISTANCE 3 4 BODY WEIGHT AND METABOLIC DYSFUNCTION INFLAMMATION METABOLISM AND TUMOR BIOLOGY No GLP-1 Risk 2.31% (2.07%, 2.55%) With GLP-1 Risk 1.62% (1.42%, 1.82%) Body weight reduction Absolute Risk Reduction (ARR) 0.69% (0.38%, 1.01%) through bariatric surgery reduces breast cancer risk. BREAST BREAST CANCER EVIDENCE: BARIATRIC SURGERY CANCER i Women with prior GLP-1 receptor agonist exposure had an absolute reduction of 0.69% Lower risk of breast cancer improve glucose control, insulin May lower chronic inflammation, Prectinical studies suggest potential in the risk of breast cancer compared with women without exposure. 2026 RR 0.56 direct effects on cellular metabolism sensitivity, and metabolic health- an important contributor (95% CI 0.44-0.71; factors linked to lower cancer risk. to tumor development. proliferation, and tumor microenvironment Conclusion: GLP-1 receptor agonist exposure is associated with an absolute <0.00001) reduction in breast cancer risk in this matched cohort. Int Mol Sci 24:6192, 2023 IAMA 331:38, 2024 Nat Cancer 7:260-271, 2026 Science (1979) 385:258-260, 2024 McDonald E et al. ASCO 2026 . TriNetX RWE Breast Cancer Outcomes with GLP-1 RAs Ongoing Clinical Trials: GLP-1 RAs in Breast Cancer RA - cause mortality - insulin or M TriNetX 68 US EMRs 10 10 0.8 0.5 Obesity or T2DM Prospective Evidence on the Horizon 0.5 0.5 PSM breast cancer Name Insuliner methermouse prognostic factors . NCT/Trial Agent BC Subtype Setting Primary Secondary Design 0.4 3.4 Obesity Pts Endpoint Endpoint Overal T2DM Pts 0.2 0.2 Diagnosis 2006 to NCT06518837 Tirzepatide HR+/HER2- Active >5% weight loss IDFS, DRFS, changes in BMI, FITWISE Trial BC (adjuvant) adjuvant body fat distribution, 00: during treatment, Prospective 2023 metabolic markers, ctDNA; Omene, C. treatment 2 $ 6 1 feasibility metabolomic pathways and Time.y 50% black immune cell metabolism ($) 13 0 945 10-yr followup pts 214 127 105 Insula 457 227 125 14 - BREAST Primary Endpoint: BREAST NCT06517212 Tirzepatide HR+/HER2- High-risk, Metastatic CIDNA clearance, TTR, Prospective CANCER CANCER TRIM-EBC Trial high-risk BC N+ early- disease DFS, Exploratory analysis All cause mortality (O'Shaughnessy stage prevention of metabolic, hormonal and Kelly) and immune cell changes Secondary: RFS Tatum KL et al. JAMA Network OPEN 2026 . --- [Slide 3] Absolute Risk Reduction (ARR) in Breast Cancer WHY GLP-1 RECEPTOR AGONISTS Within Matched Dataset (N = 30,528) MAY INFLUENCE BREAST CANCER RISK MI Purpose: To quantify the absolute reduction in the risk of breast cancer associated with prior GLP-1 receptor agonist exposure. There are several reasons to believe GLP-1 receptor agonists could influence cancer risk. REDUCE REDUCE SYSTEMIC EFFECTS ON CELLULAR Measure Estimate 95% Wald CI 1 2 IMPROVE INSULIN RESISTANCE 3 4 BODY WEIGHT AND METABOLIC DYSFUNCTION INFLAMMATION METABOLISM AND TUMOR BIOLOGY No GLP-1 Risk 2.31% (2.07%, 2.55%) With GLP-1 Risk 1.62% (1.42%, 1.82%) Body weight reduction Absolute Risk Reduction (ARR) 0.69% (0.38%, 1.01%) through bariatric surgery reduces breast cancer risk. BREAST BREAST CANCER EVIDENCE: BARIATRIC SURGERY CANCER i Women with prior GLP-1 receptor agonist exposure had an absolute reduction of 0.69% Lower risk of breast cancer improve glucose control, insulin May lower chronic inflammation, Prectinical studies suggest potential in the risk of breast cancer compared with women without exposure. 2026 RR 0.56 direct effects on cellular metabolism sensitivity, and metabolic health- an important contributor (95% CI 0.44-0.71; factors linked to lower cancer risk. to tumor development. proliferation, and tumor microenvironment Conclusion: GLP-1 receptor agonist exposure is associated with an absolute <0.00001) reduction in breast cancer risk in this matched cohort. Int Mol Sci 24:6192, 2023 IAMA 331:38, 2024 Nat Cancer 7:260-271, 2026 Science (1979) 385:258-260, 2024 McDonald E et al. ASCO 2026 . TriNetX RWE Breast Cancer Outcomes with GLP-1 RAs Ongoing Clinical Trials: GLP-1 RAs in Breast Cancer RA - cause mortality - insulin or M TriNetX 68 US EMRs 10 10 0.8 0.5 Obesity or T2DM Prospective Evidence on the Horizon 0.5 0.5 PSM breast cancer Name Insuliner methermouse prognostic factors . NCT/Trial Agent BC Subtype Setting Primary Secondary Design 0.4 3.4 Obesity Pts Endpoint Endpoint Overal T2DM Pts 0.2 0.2 Diagnosis 2006 to NCT06518837 Tirzepatide HR+/HER2- Active >5% weight loss IDFS, DRFS, changes in BMI, FITWISE Trial BC (adjuvant) adjuvant body fat distribution, 00: during treatment, Prospective 2023 metabolic markers, ctDNA; Omene, C. treatment 2 $ 6 1 feasibility metabolomic pathways and Time.y 50% black immune cell metabolism ($) 13 0 945 10-yr followup pts 214 127 105 Insula 457 227 125 14 - BREAST Primary Endpoint: BREAST NCT06517212 Tirzepatide HR+/HER2- High-risk, Metastatic CIDNA clearance, TTR, Prospective CANCER CANCER TRIM-EBC Trial high-risk BC N+ early- disease DFS, Exploratory analysis All cause mortality (O'Shaughnessy stage prevention of metabolic, hormonal and Kelly) and immune cell changes Secondary: RFS Tatum KL et al. JAMA Network OPEN 2026 . --- [Slide 4] Absolute Risk Reduction (ARR) in Breast Cancer WHY GLP-1 RECEPTOR AGONISTS Within Matched Dataset (N = 30,528) MAY INFLUENCE BREAST CANCER RISK MI Purpose: To quantify the absolute reduction in the risk of breast cancer associated with prior GLP-1 receptor agonist exposure. There are several reasons to believe GLP-1 receptor agonists could influence cancer risk. REDUCE REDUCE SYSTEMIC EFFECTS ON CELLULAR Measure Estimate 95% Wald CI 1 2 IMPROVE INSULIN RESISTANCE 3 4 BODY WEIGHT AND METABOLIC DYSFUNCTION INFLAMMATION METABOLISM AND TUMOR BIOLOGY No GLP-1 Risk 2.31% (2.07%, 2.55%) With GLP-1 Risk 1.62% (1.42%, 1.82%) Body weight reduction Absolute Risk Reduction (ARR) 0.69% (0.38%, 1.01%) through bariatric surgery reduces breast cancer risk. BREAST BREAST CANCER EVIDENCE: BARIATRIC SURGERY CANCER i Women with prior GLP-1 receptor agonist exposure had an absolute reduction of 0.69% Lower risk of breast cancer improve glucose control, insulin May lower chronic inflammation, Prectinical studies suggest potential in the risk of breast cancer compared with women without exposure. 2026 RR 0.56 direct effects on cellular metabolism sensitivity, and metabolic health- an important contributor (95% CI 0.44-0.71; factors linked to lower cancer risk. to tumor development. proliferation, and tumor microenvironment Conclusion: GLP-1 receptor agonist exposure is associated with an absolute <0.00001) reduction in breast cancer risk in this matched cohort. Int Mol Sci 24:6192, 2023 IAMA 331:38, 2024 Nat Cancer 7:260-271, 2026 Science (1979) 385:258-260, 2024 McDonald E et al. ASCO 2026 . TriNetX RWE Breast Cancer Outcomes with GLP-1 RAs Ongoing Clinical Trials: GLP-1 RAs in Breast Cancer RA - cause mortality - insulin or M TriNetX 68 US EMRs 10 10 0.8 0.5 Obesity or T2DM Prospective Evidence on the Horizon 0.5 0.5 PSM breast cancer Name Insuliner methermouse prognostic factors . NCT/Trial Agent BC Subtype Setting Primary Secondary Design 0.4 3.4 Obesity Pts Endpoint Endpoint Overal T2DM Pts 0.2 0.2 Diagnosis 2006 to NCT06518837 Tirzepatide HR+/HER2- Active >5% weight loss IDFS, DRFS, changes in BMI, FITWISE Trial BC (adjuvant) adjuvant body fat distribution, 00: during treatment, Prospective 2023 metabolic markers, ctDNA; Omene, C. treatment 2 $ 6 1 feasibility metabolomic pathways and Time.y 50% black immune cell metabolism ($) 13 0 945 10-yr followup pts 214 127 105 Insula 457 227 125 14 - BREAST Primary Endpoint: BREAST NCT06517212 Tirzepatide HR+/HER2- High-risk, Metastatic CIDNA clearance, TTR, Prospective CANCER CANCER TRIM-EBC Trial high-risk BC N+ early- disease DFS, Exploratory analysis All cause mortality (O'Shaughnessy stage prevention of metabolic, hormonal and Kelly) and immune cell changes Secondary: RFS Tatum KL et al. JAMA Network OPEN 2026 .
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Targeting the gut microbiome to manage arthralgia on aromatase inhibitorsLynn Henry

Can the gut microbiome help explain Aromatase inhibitor-associated arthralgia? Dr. N. Lynn Henry @umrogelcancer presented preliminary data linking AIMSS with lower relative abundance of "healthy bacteria" and a pilot testing resistant potato starch as a prebiotic. #DAVABreast

2026 Kona Breast Cancer Summit slide — Lynn Henry, Targeting the gut microbiome to manage arthralgia on aromatase inhibitors2026 Kona Breast Cancer Summit slide — Lynn Henry, Targeting the gut microbiome to manage arthralgia on aromatase inhibitors2026 Kona Breast Cancer Summit slide — Lynn Henry, Targeting the gut microbiome to manage arthralgia on aromatase inhibitors2026 Kona Breast Cancer Summit slide — Lynn Henry, Targeting the gut microbiome to manage arthralgia on aromatase inhibitors
[Slide 1] Differences in Relative Abundance of Phyla with AI Therapy 8 Relative Abundance Baseline weeks weeks Bacteroidota Bacillota Verrucomicrobiota Pseudomonadota Actinomycetota Synergistota Fusobacteriota BREAST CANCER Phyla 2026 HAWAII M ROGEL CANCER CENTER MICHIGAN MEDICINE --- [Slide 2] Differences in Relative Abundances of Butyrate Producers by AIMSS status p=0.0583 p=0.0035 p=0.0101 Relative abundance of Bifidobacteria Relative abundance of Blautia Relative abundance of Gordonibacter BREAST CANCER 2026 Continued Al Discontinued AI Continued Al Discontinued AI Continued AJ Discontinued AI Bifidobacteria Blautia Gordonibacter M ROGEL CANCER CENTER MICHIGAN MEDICINE --- [Slide 3] Population Differences . Al-treatment without Al-treatment MSK toxicity without MSK toxicity Al-treatment stopped - due to MSK toxicity Heat Maps Al-treatment stopped BREAST due to MSK toxicity CANCER Network Analysis 2026 Less dense, fewer edges SELITED --- [Slide 4] Next Steps Preliminary data suggests there may be an association between AIMSS development and lower relative abundance of "healthy bacteria" prior to AI initiation Conducting 20 patient pilot study of patients starting AI therapy Treating with resistant potato starch (prebiotic) X 6 mo Assessing change in bacterial composition and production of short chain fatty acids BREAST Exploratory - prevalence of discontinuation of initial AI therapy CANCER by 6 months 2026 MAWAII BCRF - Clinicaltrials.gov NCT07443943 M ROGEL CANCER CENTER MICHIGAN MEDICINE
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Fisetin, a naturally occurring flavonoid to inhibit senescenceMina Sedrak
Hormone Replacement therapy in curable HR+ BCMilana Dolezal

CDK4/6 Inhibitors in ER+ Breast Cancer

Moderator · Massimo Cristofanilli
AM3 of 5 with slides

Starting Now: CDK4/6 Inhibitors in ER+ve Breast Cancer Moderated by Dr. Massimo Cristofanilli @WeillCornell #DAVABreast

2026 Kona Breast Cancer Summit — CDK4/6 Inhibitors in ER+ Breast Cancer session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Panel on CDK4/6 inhibitors #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — CDK4/6 Inhibitors in ER+ Breast Cancer session
[Slide 1] R & DAVAOncology facilitating successful drug development ..facilitating DAVAOncology successful drug development DAVAOncology facilitating successful drug development & & KONA @ BREAST CANCER SUMMIT in & DAVA Oncology davaonc.com D 8 & BREAST CANCER 8 2026 HAWAII & & DAVAOncology ...fecilitating DAVAOncology successful drug development DAVAOncology facilitating successful drug development facilitating successful DAVAOralog ncology ology CO & AOncing DAVAOncology DAVAOncology™ DAVAG DAVAOrcology DAVAOrcology DAVAOncology DAVAOncology DAVAOncology DIVAOralogy AVAOrology DAVAOcodogy DAVAOncology DAVAOncology™ NAOncology DWAOneology DAVAOncology
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PostMONARCH: CDK4/6 inhibition following failure of a CDK4/6 inhibitorPriyanka Sharma

Following CDK4/6i progression, what's next? Dr. Priyanka Sharma @KUMedCenter reviews postMONARCH: switching endocrine therapy + abemaciclib improved PFS; palbociclib after palbociclib did not. Imlunestrant + abemaciclib showed 9.1-mo mPFS in EMBER-3. #DAVABreast

PostMONARCHprofileEMBER-3profile
2026 Kona Breast Cancer Summit slide — Priyanka Sharma, PostMONARCH: CDK4/6 inhibition following failure of a CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Priyanka Sharma, PostMONARCH: CDK4/6 inhibition following failure of a CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Priyanka Sharma, PostMONARCH: CDK4/6 inhibition following failure of a CDK4/6 inhibitor2026 Kona Breast Cancer Summit slide — Priyanka Sharma, PostMONARCH: CDK4/6 inhibition following failure of a CDK4/6 inhibitor
[Slide 3] Kaplan-Meier / survival curve — table and text data only
No PFS improvement with palbociclib + switching ET post-palbociclib: PACE trial Median PFS PFS, mo 6-month PFS: Pts Events P-value Percent alive and progression-free 12-month PFS: FUNNIT BREAST CANCER HAWAII Months since randomization Meyer et al. JCO 2024
[Slide 4] Kaplan-Meier / survival curve — table and text data only
PFS improvement with imlunestrant + abemaciclib: EMBER-3 Patients with prior CDK4/61 treatment informetrant Insurestrant abemacicib imjunestrant Imlunestrant THE abemacicito No. events No. events Median 90% CIL Months Progression-free Survival (%) Median (95% CI). months Time (months) Patients with ESRIm Patients without ESRIM Insurestent 60% prior CDK4/6i No. af events - devers Median Palbo (~ 65%)> Ribo (~ 25%) >Abema (~ <10%) BREAST months nonths CANCER HAWAI Jhaveri et al. NEJM 2024
[Slide 1] Randomized phase III trial of abemaciclib + switching ET post CDK4/6i progression: postMONARCH trial Eligibility Primary Endpoint: Investigator-Assessed PFS HR+, HER2- ABC Abemaciclib + Fulvestrant Secondary Endpoints: Men & Pre/post menopausal women Randomization 1:1 OS, PFS by BICR, ORR, CBR, DCR, DoR, Safety, PK N 368 Prior Therapy: & PRO ABC: Disease progression on CDK4/6i AI as initial therapy Stratification Factors: Adjuvant: Disease recurrence Placebo + Fulvestrant Duration of prior CDK4/6i on/after CDK4/6i ET Visceral metastases No other therapy for ABC Geographic region BREAST CANCER 2026 HAWAII ~59% prior palbo - 60% visceral metastases, 0% prior chemo for MBC Kalinsky et al. JCO 2025 --- [Slide 2] PFS improvement with abemaciclib plus swiching ET post- CDK4/6i: postMONARCH Placebo Fulvestrant N 182) Fulvestrant N 186) M Survice 2 - Events 117 141 N Median (95% Ci) S.O 5.3 months 5.8-3.0) (37-5.6) - HR (95% Ci) 0.73 (0.57 0.95) - nominal 0.02 - - . Packso kin " n hills interaction p-walle ********* Liver 14) J - 09 m . , ' . 2 n. 30 s - a IN (4) 078,036,108 Time (Porths) Bone-Only Disease in - : = " : : : - N 4 No - N - N States 195 Abemacicilb Placebo + Patie 24 271 Fulvestrant Fulvestrant I N - 181 N 185 9 52 ON Pricr COME Duration 163 BREAST % 272 a Grade TRAE', I CANCER 1 (0.6) 0 - COLLS 12 a in (%) I PJ Pricr COKEN 15 Dose reductions due to AE, (%) 55(30) 6(3) 217 45 | 2026 HAWAII M = X Discontinuations Ademacide 25 1 11(6) 0 due AE, (%) 14 11 a 12 214 18 Kalinsky et al. JCO 2025
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Potential use of ctDNA to delay initiation of CDK4/6 therapyMarko Velimirovic

Can ctDNA guide when to escalate therapy in HR+/HER2- breast cancer? @marko_velimir @fredhutch outlines a study of molecular vs radiographic progression, with TSST as the primary endpoint and delayed CDK4/6i aiming to preserve QoL without compromising survival. #DAVABreast

2026 Kona Breast Cancer Summit slide — Marko Velimirovic, Potential use of ctDNA to delay initiation of CDK4/6 therapy2026 Kona Breast Cancer Summit slide — Marko Velimirovic, Potential use of ctDNA to delay initiation of CDK4/6 therapy2026 Kona Breast Cancer Summit slide — Marko Velimirovic, Potential use of ctDNA to delay initiation of CDK4/6 therapy2026 Kona Breast Cancer Summit slide — Marko Velimirovic, Potential use of ctDNA to delay initiation of CDK4/6 therapy
[Slide 1] Background - ctDNA dynamics predicting Radiographic Progression (RP) A Rise in ctDNA tumor fraction under treatment pressure, regardless of treatment modality (cytotoxic chemotherapy targeted agents, combination therapy) can predict RP MAP MAF(%) ctDNA clearance was 100% predictive of freedom from RP Rise in ctDNA from undetectable levels at baseline was predictive of RP Baseline Genomic Radiologic VIDNA Genomic progression was indicative of RP 6 B weeks (4-12 weeks) in advance BREAST CANCER 2026 HAWAII MAR 0 Baseline Restaging bone Issueline decrease Velimirovic et al, JCO-PO 2020 - --- [Slide 2] Background - ctDNA dynamics and outcomes objective SONIA trial demonstrated and I that deferring CDK4/6i to second-line therapy is not Il ' inferior to first-line use of I I CDK4/6i. However, post hoc analysis demonstrated a BREAST difference in OS based on CANCER menopausal status. 2026 HAWAII Wortelboer et al, JAMA Oncology 2026 --- [Slide 3] Switching therapy at molecular VS at radiographic progression? S Inconsistencies in study designs across studies attempting to answer this question Lack of crossover (SERENA-6) BREAST CANCER What is the adequate primary endpoint: PFS2 vs TSST? 2026 HAWAII --- [Slide 4] Study schema- - LOW-RISK GROUP (A) HR+/HER2- ADVANCED BREAST CANCER KEY ELIGIBILITY CRITERIA Postmenopausal women and men ER+ (>10%) HER2- (IHC 0-2+, not amplified by ISH) COKA/SI No prior therapy in metastatic setting ESR1. If recurrent, >1 year of completion of FULVESTRANT CDK4/6 adjuvant endocrine therapy FULVESTRANT CDKA/91 *GEDATOLISIS NEXT TREATMENT Measurable disease per RECIST v1.1 ENDPOINTS No PIK3CA/AKT1/PTEN alterations ORAL SERD * CDK4/91 Cap bone-only disease to 10% ESR1+ PRIMARY Time to Second Subsequent Therapy (TSST) SECONDARY AI Rising CIDNA TF No radiographic PD R os monotherapy PFS per RECIST Time to chemotherapy/ADC Radiographic PD PROs Gol. metrics OFF they cIDNA clearance dynamics ESR Im emergence All CDK4/8 FDG PET SUV delta bone ESR1- FULVESTRANT CDK4/61 only BREAST AI RP FULVESTRANT COKA/SI GEDATOLISIS NEXT TREATMENT CANCER monotherapy ORAL SERD + CDK4/6I 2026 ESR1+ HAWAI : : # = # : Every 12 works 63 00 68 85 85 "
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Phase II palbociclib + tamoxifen as first-line therapy for HR+ MBCOana Danciu

Oana Danciu, MD @UICancerCenter reports phase II data of palbociclib + tamoxifen as 1L therapy in HR+/HER2- MBC achieved ORR 30%, CBR 64%, mPFS 8.7 mo, and 2-y OS 76.5%; the study notes lower PFS vs standard AI + CDK4/6i. #DAVABreast

2026 Kona Breast Cancer Summit slide — Oana Danciu, Phase II palbociclib + tamoxifen as first-line therapy for HR+ MBC2026 Kona Breast Cancer Summit slide — Oana Danciu, Phase II palbociclib + tamoxifen as first-line therapy for HR+ MBC2026 Kona Breast Cancer Summit slide — Oana Danciu, Phase II palbociclib + tamoxifen as first-line therapy for HR+ MBC2026 Kona Breast Cancer Summit slide — Oana Danciu, Phase II palbociclib + tamoxifen as first-line therapy for HR+ MBC
[Slide 3] Kaplan-Meier / survival curve — table and text data only
ParameterEfficacy evaluable patients (N=47)
Objective Response (N)14
CR0
PR14
Objective response rate (%)30
Clinical Benefit
(PR/CR or SD lasting 24 weeks or longer) (N)30
Clinical Benefit rate (%)64
Best Response (N/%)
PR14 (30%)
SD24 (51%)
PD9 (19%)
Median PFS (months)8.7
2-year Overall Survival rate76.5%
Results- Efficacy Summary Parameter Efficacy evaluable patients (N=47) Objective Response (N) Objective response rate (%) Clinical Benefit (PR/CR or SD lasting 24 weeks or longer) (N) Clinical Benefit rate (%) Best Response (N/%) Median PFS (months) 2-year Overall Survival rate
[Slide 1] Study Design and Treatment Plan Non-randomized, single arm, phase II study of Palbociclib in combination with Tamoxifen Sample size : 47 patients Drug Dose Route Schedule Cycle Length Drug administration Palbociclib 125mg Oral Days 1-21 28 days Tamoxifen 20mg Oral Continuous TERMIT - REAST CANCER Treatment continued until disease progression, unacceptable toxicity or patient refusal 2026 HAWAI --- [Slide 2] Patients Demographics S Parameter N % Sex Female 47 100 Race White 31 66 Black or African American 11 23 Asian 1 2 American Indian or Alaska Native 1 2 s Unknown 3 6 Ethnicity Hispanic or Latino 3 6 Non-Hispanic 44 94 ECOG Performance status 0 31 66 1 15 32 2026 HAWAII 3 2 1 2 Menopausal status Post-menopausal 38 81 Pre-menopausal 9 19 --- [Slide 4] Results-Summary of Most Common AEs (all grades) / Toxicity description Toxicity grade (% of patients, highest grade per patient) 1 2 3 4 Total Neutropenia 1 9 33 5 37 Anemia 11 9 2 0 22 Thrombocytopenia 19 1 0 0 20 Lymphocytopenia 4 6 2 0 12 Fatigue 17 20 0 0 37 Nausea 19 6 2 0 27 Infections 6 24 2 0 32 FORMET ON REAST Hot flashes 13 4 0 0 17 CANCER Alopecia 11 1 0 0 12 2026 HAWAI Diarrhea 10 4 2 0 16 Anorexia 8 6 0 0 14 Four patients developed thromboembolic events (1 grade 2,2 grade 3 and 1 grade 4) One patient died while on treatment from POD; Nine Palbociclib dose reductions, due to neutropenia
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Biomarkers to predict resistance to CDK4/6 inhibitorsAnton Safonov
Biomarkers for CDK4/6 resistance from preclinical analysesToshi Iwase

Updates in Adjuvant Trials in ER+ Breast Cancer - I

Moderator · Sandra Swain
AM5 of 7 with slides

Starting Soon: Updates in Adjuvant Trials in ER+ve Breast Cancer Moderated by Dr. Sandra Swain @Georgetown #DAVABreast

2026 Kona Breast Cancer Summit — Updates in Adjuvant Trials in ER+ Breast Cancer - I session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Panel on adjuvant therapy in ER+ve BC #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Updates in Adjuvant Trials in ER+ Breast Cancer - I session
[Slide 1] ...facilitating successful drug development ...facilitating successful drug development ...facilitating successful drug development KONA BREAST CANCER SUMMIT in www DAVA Oncology davaonc.com & "SUMMIT ON BREAST D CANCER 2026 HAWAII CANCER MODERATOR & DAVAOncology facilitating DAVAOncology successful drug development DA ...facilitating successful drug development ..facilitation DiVAOnalog ncology ology 8 S DAVAOno AVAQ DAVAOncology™ DAVAOncology DAVAOncology DAVAOncology™ DAVAG DAVAOrcology DAVAOrcology® DAVAOncology™ DAVAOncology® DAVAOncology™ MAOncology™ DAVAOnalogy DAVA DAVAOncology ,
VVinay Jain@VinayJaink9vh2026-08-20Source post on X ↗
Abemaciclib dose optimization approaches in early stage breast cancerAntonio Giordano
Update on the lidERA trial of giredestrant as adjuvant therapyAdam Brufsky

Dr. Adam Brufsky @breastoncdoc @UPMCHillmanCC reviews lidERA: adjuvant giredestrant reduced the risk of invasive disease recurrence or death by 30% vs SOC endocrine therapy in ER+/HER2− early breast cancer, with IDFS benefit across key prespecified subgroups. #DAVABreast

lidERAprofile
2026 Kona Breast Cancer Summit slide — Adam Brufsky, Update on the lidERA trial of giredestrant as adjuvant therapy2026 Kona Breast Cancer Summit slide — Adam Brufsky, Update on the lidERA trial of giredestrant as adjuvant therapy2026 Kona Breast Cancer Summit slide — Adam Brufsky, Update on the lidERA trial of giredestrant as adjuvant therapy2026 Kona Breast Cancer Summit slide — Adam Brufsky, Update on the lidERA trial of giredestrant as adjuvant therapy
[Slide 2] Kaplan-Meier / survival curve — table and text data only
lidERA fined Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM Primary endpoint: IDFS UT Health AACR Giredestrant SOC ET Events, n (%) 140(6.7) Stratified HR IDFS 2 FUNNIT DE BREAST Time (months) CANCER No. risk Giredestrant SOC Median follow-up: 32.3 months HAWAI Statistically significant and clinically meaningful improvement in IDFS: Giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with SOC ET Data culeff August 1. 2025 Median follow-up up. 32 months - the presentant am and 12 1 months - the SOC ET arm mainium follow-up 46 months and 46.3 months, respectively Logirank (2) wood) - boundary for IDFS interm analysis - 0217 sided) Al, 4/07/2004 inhibitor CL confidence interval; ET. endocrine therapy HR, hazard noc OFS invisive disease free survives soc. standard-of-care Presented by Aditya L Bardia, MD This presentation the intellectual property the Contact for permission reprint and/or distribute
[Slide 1] SAN ANTONIO lidERA Breast Cancer study design BREAST CANCER SYMPOSIUM - Health AAGR A global, randomized, open-label, multicenter Phase III trial At least 5-year treatment duration 5-year follow-up Key eligibility criteria Participants with ER+, negative early breast cancer N 4170 Stage I-III disease (anatomical) Giredestrant (30 mg PO QD) pN0 and pT > 1 cm with Grade 3, or Ki67 2 20% R Long-term or high score on genomic assay," or pT4N0 1:1 follow-up Node-positive SOC ET Pre- or post-menopausal? Tamox/fen/anastrozole/etrozole/evemestane Breast cancer surgery within 12 months (Neo)adjuvant chemotherapy if indicated Stratification factors Primary endpoint Risk: Medium-1 vs high-risk Stage I-III breast cancer IDFS (excluding second primary non-breast cancer) Region USA/Canada/Western Europe vs Asia-Pacific vs RoW Key secondary endpoints Previous chemotherapy: No vs yes DFS, DRFI, IDFS (including second primary non-breast invasive cancer with exception of BREAST Menopausal status: Pre-menopausal vs post-menopausal non-melanoma skin cancers and in situ carcinomas of any site), LRRFI, OS, safety CANCER Giredestrant is currently also being investigated in combination with abomaciclib in the adjuvant setting (lidERA Breast Cancer substudy 1) 2026 Enrollment August 2021 to September 2023 Up to 12 WORKS of CT COKES were allowed ER+ was defined as . 1% positive cells by immunahistochemistry OncotypeDw 25 or high-risk Mammaprint HAWAII menopausal patients on aromatase inhibitors or giredestrant had to receive ovarian function suppression with an approved uteinizing homore- releasing hormone agentst Medium - DND and primary furner on with high-rist biologic features (Grade or K067 20% or high score on genoric essay or available) and pN1 with OW risk biologic features Grade 1/2 and K67 . 20% and - 45 on and low score on assay if available) High nak pT4 or pN2 or (N) and INT with high-nsk biologic features (Grade 3. or KET 20% or turnor -5 on or high score on genomic essay If available) COKA/SI, cyclin-dependent kindse 4/6 inhibitor, OFS. - Yes survival ORFI distant recurrence free interval, ER+ estrogen receptor positive ET endoctine therapy OFS, - damate free survival LRRFI locoregional recurrence free interval os overall survival PO. orazy. QD once daily R. randomization Row rest of the world soc standard-of-care ClinicalTrals gov number NCT04961996 Adapted from Geyer CE, of ASCO TPS616) with permission Presented by: Aditya L Bardia, MD. This presentation the intellectual property of the presenter Contact for permission reprint and/or distribute --- [Slide 3] lidERA fireast Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM IDFS in key subgroups 5 Health AACR Patients, " Total, n Giredestrant HR (95% CD) 4170 2006 s All patients 2084 0.70(0.57.087) Age group, years $45 906 472 434 0.81(0.50,1.33) +45 30 55 1355 660 695 0.54(0.36,0.90) 1118 567 551 0.77 (0.53, 1.13) 45 791 385 406 0.82(0.49,1.36) Region Asia- Pacific 1068 544 544 0.70(0.44,1.12) Latin America/Afica/tasiom Europe 1317 680 637 0.68(0.51,0.92) USA/Canada/Western Europe 1765 560 905 0.68(0.44,1.04) Menopausal status Pre-menopausal 1680 541 539 0.65(0.44,0.95) Post-menopausal 2490 1243 1247 0.73(0.56,0.95) AJCC stage at surgery" 537 254 263 0.89(0.42,1.90) I I 1963 1013 950 0.58(0.39,0.85) " 1643 799 544 0.74(0.56,0.98) Risk High 2895 1448 1447 0.69(0.55,0.88) Medium 1275 636 639 0.74(0.42,1.31) NUMBER OR Previous chemotherapy No 787 392 395 0.63(0.33,1.21) BREAST Yes 3383 1692 1691 0.71(0.57,0.90) CANCER 02 0.4 04 DA 10 12 14 16 18 20 Giredestrant better soc ET batter 2026 / MAWAII personner IDFS benefit was consistent across key prespecified subgroups Data cutoff August 5. 2025 HR estimates are unstratified Median follow up or 12 months in the giredestrant arm and 32 months in - soc ET ann, maximum follow- - 40. months and 46 months respectively One patient had Stage desase ISOC ET arm): 26 had unknown Stage (18 in the giredestrant arm and eight the SOCIT am) AJCC American Joint Committee on Cancer, CI, confidence interval ET endocrine herapy HR, hazard ratio OFS, invasive disease tree survival soc, standand-of Presented by Aditya L Bandia, MD. This : a . the property of the presenter Contact for permission to reprint distribute 13 --- [Slide 4] lidERA I Cancer SAN ANTONIO BREAST CANCER SYMPOSIUM AE overview (safety-evaluable population) Health AAGR - Common TEAEs (> 7.5% of patients in either arm at any grade) Selected AEs Giredestrant Giredestrant n - 2060 SOC ET n 2074 n= n 2060 2074 Arthralgia 1.5/46.5 45.3/1.8 Patients, n (%) with treatment discontinuations due to AEs Hot flush 0.3/27.1 28/03 Headache 0.1/152 13.1/0.1 Musculoskeletal disorders 38 (1.8) 92 (4.4) Fatigue Arthralgias (PT) 32(1.6) 76 (3.7) Insomnia Vasomotor disorders 2(<0.1) 18(0.9) Nausea COVID-19 Hot flush (PT) 1(<0.1) 16(0.8) Asthenia Giredestrant M n= 2060 n=2074 Back pain Radiation skin injury Patients, n (%) with treatment discontinuations due to AEs Hypertension G2 G3-4 G1 G2 G3-4 Urinary tract infection 15 Bradycardiat 0 64 2 0 Cough (0.7) (3.1) LA (<0.1) BREAST Diarrhea Giredestrant soc IT Venous Thromboembolic 12 2 3 7 7 CANCER Pain in extremity G1-2 events (0.6) (<0.1) (0.1) (0.3) (0.3) Constipation G3-4 2026 -60 40 30 -20 -10 0 to 20 30 40 50 Patients (%) Data cutatt August 8. 2025 Assessed as medical concepts using grouped terms, at other AEs by medical concept were comparable between arms, including four patients per arm (0.2%) who experienced photopsia G2 events occurred in 7 gatients 13 resolved four patients discontinued treatment and the events resolved G3 only At. adverse event IT. endocrine therapy G. grade PT. preferred term; soc, standard-of-care TEAE treatment treatment-emergent emergent adverse event, Presented by Aditya L Bardia, MD. This presentation - the intellectual property of the presenter Contact for permission to reprint and/or distribute
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Trials with elacestrant in early-stage ER+ breast cancerAdriana Kahn

From neoadjuvant to ctDNA-guided adjuvant therapy, @AdrianaKahnMD @YaleCancer reviews elacestrant in early ER+/HER2- BC: ELIPSE reduced Ki67 by 52.9%, while ELEGANT and CATE are evaluating adjuvant use in high-risk and ctDNA-positive disease. #DAVABreast

ELEGANTELIPSE
2026 Kona Breast Cancer Summit slide — Adriana Kahn, Trials with elacestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Adriana Kahn, Trials with elacestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Adriana Kahn, Trials with elacestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Adriana Kahn, Trials with elacestrant in early-stage ER+ breast cancer
[Slide 1] Early-Stage Setting SOLTI-ELIPSE: neoadjuvant elacestrant for node-negative ER- positive HER2-negative breast cancer ELEGANT trial: adjuvant elacestrant vs SOC endocrine therapy for high-risk ER-positive HER2-negative breast cancer CATE (TBCRC-064): adjuvant elacestrant for ctDNA positive high-risk ER-positive HER2-negative breast cancer after completion of adjuvant endocrine therapy BREAST CANCER 2026 HAWAII YaleNewHavenHealth Yalemm Smilow Cancer Hospital --- [Slide 2] SOLTI-ELIPSE: Elacestrant in Women with Estrogen Receptor- Positive and HER2-Negative Early Breast Cancer: Results from the Preoperative Window-of-Opportunity ELIPSE Trial Key eligibility criteria (N=24) 28 days (+/- 2 days) Post-menopausal women Histologically confirmed, operable invasive breast Elacestrant 1-28 days Screening 400 mg orally Surgery** carcinoma Once daily End of Study T1c (>15 mm) -T3 by ultrasound cN0, cMO ER-positive (21%)* Mandatory pre- treatment biopsy OR anchival tissue HER2-negative* Locally assessed Ki67>10% BREAST Mandatory post- ER, estrogen receptor treatment sample CANCER 2026 As per local assessment and based on ASCO/CAP guidelines Primary Complete Cell Cycle Arrest (CCCA) Tumor biopsy is taken if surgery cannot be performed on Endpoint (centralized Ki6752.7%) day 28(+/- days) YaleNewHavenHealth Yalemm Vidal et al, CCR 2025 Smilow Cancer Hospital Clinicaltrials.gov: NCT04797728 --- [Slide 3] ELEGANT: Elacestrant versus standard endocrine therapy in women and men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study Patient Population PHASE 3 Node-positive, ER+/HER2- eBC with Elacestrant PHASE 3 OBJECTIVES high recurrence risk who 345 mg" QD Primary: Evaluate IBCFS received between 2-5 years of SOC ET : CDK4/6i R Key secondary: Evaluate DRFS and OS LHRH agonist will be 1:1 Secondary: Evaluate IDFS', safety, Continue ET' PROs-QoL and PK administered for Anastrozole mg DD Letrozole 2.5 mg QD. pre/perimenopausal Exemestane 25 mg QD or Tamoxifen 20 mg QD Exploratory: Evaluate cfNA and bone health women and men. N=4220 5 years STRATIFICATION FACTORS BREAST Menopausal status (pre/perimenopausal vs post-menopausal and men) CANCER Prior CDK4/6i treatment in the adjuvant setting (yes vs no) 2026 Time since curative surgery (s4 years vs >4 years) Bardia et al. J Clin Oncol 44, 2026 YaleNewHavenHealth Yale (suppl 16; abstr TPS1153) Smilow Cancer Hospital Clinicaltrials.gov: NCT06492616 --- [Slide 4] A single arm phase-II trial of circulating tumor DNA-guided adjuvant therapy with elacestrant in adults with hormone receptor positive HER2 negative breast cancers at risk for late recurrence (CATE, TBCRC-064) S The recurrence risk in ER-positive breast cancer remains persistently elevated as far as 20 years from diagnosis There is increasing evidence that circulating tumor DNA is a sensitive and specific assay for predicting distant recurrence This trial is the first study to investigate ctDNA positivity in patients at risk for late recurrence who are already off ON BREAST endocrine therapy CANCER 2026 HAWAII YaleNewHavenHealth Yale Courtesy of study PI: Smilow Cancer Hospital Mariya Rozenblit
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Trials with imlunestrant in early-stage ER+ breast cancerJoyce O'Shaughnessy

Joyce O’Shaughnessy, MD @BCJoyceO @TexasOncology reviews imlunestrant in ER+/HER2− early breast cancer, highlighting biomarker findings from EMBER-2 and the ongoing EMBER-4 trial assessing adjuvant use after 2-5 years of endocrine therapy. #DAVABreast

EMBER-2EMBER-4
2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Trials with imlunestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Trials with imlunestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Trials with imlunestrant in early-stage ER+ breast cancer2026 Kona Breast Cancer Summit slide — Joyce O'Shaughnessy, Trials with imlunestrant in early-stage ER+ breast cancer
[Slide 1] Kaplan-Meier / survival curve — table and text data only
EMBER-3 SAN ANTONIO Updated PFS BREAST CANCER SYMPOSIUM Imlunestrant VS SOC ET in Patients With ESR1m THesis AACR Imlunestrant SOC ET No. of events Progression-free Survival (%) Median (95% CI) Nominal p-value* = 0.0007 infunestrant SOCET BREAST CANCER Time (months) No at msk HAWAII Jhaveri K et al. Ann Oncol 2026
[Slide 2] Study Design EMBER-2: A Phase 1. Open-Label, Randomized Study in Postmenopausal Women With Stage I-III ER+, HER2- EBC Imlunestrant 800 mg Primary Endpoint . QD POx2 weeks Initial (n=28) Change in ER expression between pretreatment and posttreatment turnor samples randomization Postmenopausal 1:1 women with Imlunestrant 400 mg Stage I-III, ER+, -15 days QD POx2 weeks Surgical resection or HER2- EBC (n=30) posttreatment biopsy (N=87) Ad hoc nonrandom Imlunestrant 200 mg assignment QD POx2 weeks (n=28) Stratification factors: BC subtype, IDC vs. ILC vs. Other Day 1 Day 15 BREAST CANCER PD sample: Pretreatment tumor tissue PD sample: Not collected PD sample: Posttreatment tumor tissue PK sample: Not collected PK sample: Pre and post-dose blood PK sample: Pre and post-dose blood sample at first dose sample at steady state 2026 HAWAII Patients were nonrandomy assigned " the 200-mg cohort, which was included in EMBER 2 after protocol amendment 00 evaluate the PD effects of dose reduction option "One out of the 87 patients was never I BC-Breast Cancer EBC=Eaty Breast Cancer, ER=Estrogen Receptor HER2=Human Epidermal Growth Factor Receptor 2. IDC=Invasive Ductal Carcinoma ILC-Invasive Lobular Carcinoma QD=Once . Day PO-Phamacodynamics PO-by mouth Never P. et et al . City Cancer Pas 2024 30(23) 5304-5313 --- [Slide 3] EMBER-4 (NCT05514054) Study Design ember-4 A Randomized, Open-Label, Phase 3 Study of Adjuvant Imlunestrant vs Standard CLINICAL TRIAL Adjuvant Endocrine Therapy in Patients who have Previously Received 2 to 5 years of Adjuvant Endocrine Therapy for ER+, HER2- Early Breast Cancer with an Increased Risk of Recurrence Imlunestrant Primary Objective: 400 mg PO QD ER+/HER2- EBC patients who have IDFS, excl 2nd non-breast primary (5 years) received 2-5 years of adjuvant ET* Key Secondary Objectives: with an increased risk of R 1:1 N 8000 Distant relapse-free survival recurrence based on clinical- Investigator's choice ET Overall survival pathological risk features IDFS, incl 2nd non-breast Tamoxifen or Alb primary (5 years) Patient-reported outcomes N2 or N3 BREAST FPI October 2022 N1 and T3/T4 or grade 3 or T2 and grade 2 CANCER First results Q4 2027 or Q1 2028 NO and T3/T4 or T2 and grade 3 2026 Prior adjuvant therapy with a COKAN or PARP inhibitor is permited Excluded " month consecutive gap in ET or I completed or discontinued ET> 6 months prior to screening "GriRH Agenist is required in men and menopausal women receiving interestant or At and a given - the investigator . discretion in patients receiving tamoxifon per standard practice Clinical Trials gov --- [Slide 4] preEMBER (NCT07287098, J2J-MC-JZLL): A Phase 2, Open-label Study Evaluating Imlunestrant in Premenopausal Women With ER+, HER2- Breast Cancer1,2 Premenopausal women with ER+, HER2-BC Stage 1. III disease Early-stage, resected, invasive breast cancer without evidence of Ki-67 >10%, per local assessment distant metastasis Scheduled for curative surgery or agrees to on-treatment biopsy Undergone definitive locoregional therapy of the primary index breast tumor(s) Received at least 4.5 years of adjuvant ET, or at least 2 years of adjuvant ET with no further OFS planned Cohort 1: Window of Opportunity Cohort 2: Ovarian Safety Assessment Imlunestrant Imlunestrant Pre-treatment R 2:1 1:1:1 tumor Imlunestrant Goserelin Primary Surgical N=300 N=300 Resection or Biopsy Tamoxifen sample BREAST Tamoxifen CANCER 6 months 2026 28 Days MAWAII Primary endpoint: change from baseline in Ki-67 expression Primary endpoint: rate of symptomatic ovarian cysts a Secondary endpoint: change from baseline in ER/PR expression; safety Secondary endpoint: rate of complex ovarian cysts; safety 1. hitps: govistudy/NCT07287098 (Accessed February 5, 2026) 2. Data an the Clinical Protocol Amentment (4)
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Adjuvant switching on SERD: insights on ELEGANT and EMBER-4Ajay Dhakal

Can switching adjuvant ET to a SERD improve outcomes in high-risk ER+/HER2- EBC? @DhakalAjay @WilmotCancer compares ELEGANT and EMBER4, evaluating elacestrant and imlunestrant after prior adjuvant ET with invasive disease outcomes as key endpoints. #DAVABreast

ELEGANTEMBER-4
2026 Kona Breast Cancer Summit slide — Ajay Dhakal, Adjuvant switching on SERD: insights on ELEGANT and EMBER-42026 Kona Breast Cancer Summit slide — Ajay Dhakal, Adjuvant switching on SERD: insights on ELEGANT and EMBER-42026 Kona Breast Cancer Summit slide — Ajay Dhakal, Adjuvant switching on SERD: insights on ELEGANT and EMBER-42026 Kona Breast Cancer Summit slide — Ajay Dhakal, Adjuvant switching on SERD: insights on ELEGANT and EMBER-4
[Slide 1] Elacestrant (Emerald Trial) Elacestrant Inclusion Criteria 400 mg orally daily Men and postmenopausal women with N=477 advanced/metastatic breast cancer PD or Primary Endpoints." withdrawal PFS in all patients ER-positive,* HER2-negative criterion PFS in mESRI Progressed or relapsed on or after 1 or 2 lines R Follow-up Key Secondary of endocrine therapy for advanced disease, Endpoints: one of which was given in combination with 1:1 investigator's choice (SOC): os in all patients CDK4/61 Fulvestrant os in mESRI $1 line of chemotherapy for advanced disease Anastrozole ECOG PS 0 or 1 Letrozole Exemestane Stratification Factors: SRI mutation status* Prior treatment with fulvestrant Presence of visceral metastases BREAST CANCER 2026 HAWAII EMERALD Trail. Bidard et. al. J Clin Oncol 40, 3246-3256(2022) NCI Cancer Center 2026 KONA Breast Cancer Summit UR WILMOT MEDICINE CANCER INSTITUTE --- [Slide 2] Imlunestrant (EMBER 3 Trial) EMBER-3: A Phase 3, Randomized, Open-Label Study in Patients With ER+/HER2- ABC (NCT04975308) Primary Endpoints Men and women (with any menopausal PFS by investigator assessment as per status) aged a18 years with Arm A RECIST. v1.1 ER+/HER2-ABC Imlunestrant Monotherapy Arm A vs Arm 8 in patients with ESRI 400 mg QD PO mutations Prior therapy: Arm A vs Arm B in all patients Adjuvant Recurrence on or within 12 Arm C vs Arm A in all patients/ months of completion of AI alone or in combination with a CDK4/6 inhibitor Secondary Endpoints ABC Progression on first-line AI alone Arm B Overall survival (key endpoint) or in combination with a CDK4/6 RICEIP Standard of Care* For at the 3 groups as mentioned under the inhibitor (N=874) (Fulvestrant 500 mg M°or primary endpoint No other previous therapy for ABC Exemestane 25 mg QD PO) PFS assessed by BICR Overall response rate Stratification factors Clinical benefit rate Previous CDK4/6 inhibitor treatment Duration of response Yes/No Arm & Safety - Visceral metastases: Yes/No BREAST Imlunestr 400 mg Geographic region East Asia/North QD PO Abemaciclib Exploratory Endpoints CANCER America or Western Europe/Others 150 mg BID PO PFS & overall survival Please refer to Appendix for Patient Disposition Arm c is Arm B in all patients' 2026 EMBER3 Trial. Jhaveri et. al. N Engl J Med 2025;392:1189-1202. Slide provided by Eli Lilly NCI Cancer Center 2026 KONA Breast Cancer Summit UR WILMOT MEDICINE CANCER INSTITUTE --- [Slide 3] The Idea of the Switch Strategy is Attractive New SERD x 5years Adjuvant ER+ HER2- Breast 2-5 years of ET Cancer Patients Continue the same ET X 5 years Enriching the study population for the ESR1 mutation favoring SERD Biases affecting the selection of patients and potentially reported tolerance: 1. for patient to the BREAST 2. Novelty bias: CANCER esp. for patients with intolerance to current 31 2026 More likely to enroll, ?more likely to like the new drug MAWAII NCI Cancer Center 2026 KONA Breast Cancer Summit se UR WILMOT MEDICINE CANCER INSTTTUTE --- [Slide 4] ELEGANT EMBER 4 Endpoints Primary: Primary: IBCFS IDFS (Excluding Non-breast Second primary) Secondary: Secondary: DRFS DRFS OS OS IDFS (Including non-breast second primary) IDFS (Including non-breast second primary) Safety endpoints Safety endpoints Population Gotten 2-5 years of ET in adj settings Gotten 2-3 years of ET in adj settings High Risk: High Risk: a.24 positive axillary lymph nodes OR a. >4 ipsilateral positive LN b. 1 - 3 positive axillary lymph nodes AND one of the b. 1-3 ipsilateral positive LN and one of the following following: criteria must also be present: i. Histologic grade 3 disease i. Histologic grade 3 disease ii. Tumor size >5 cm ii. Tumor size 2 5 cm iii. High genomic risk (identified by Oncotype, iii. Tumor size >2 cm but <5 cm and histologic Grade MammaPrint, EndoPredict, PAM50). 2 BREAST c. no positive LN and one of the following criteria CANCER must also be present: 2026 i. tumor size >5 cm MAWAI ii. tumor size >2 cm but <5 cm and histologic Grade 3 N 4220 (anticipated accrual in few months) 8000 (completed accrual) NCI 2026 KONA Breast Cancer Summit UR WILMOT MEDICINE CANCER INSTITUTE
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Adjuvant CDK4/6 inhibition + endocrine therapy for older womenYelena Novik
SWOG 2206: Neoadjuvant chemoimmunotherapy in ER+/HER2- selected by MammaPrintErin Cobain

Who may benefit from neoadjuvant chemoimmunotherapy in HR+/HER2- BC? Erin Cobain, MD @UMRogelCancer reviews MammaPrint High 2 tumors and SWOG S2206, randomizing stage II-III disease to AC-T ± durvalumab, with IDFS as the primary endpoint. #DAVABreast

SWOG S2206
2026 Kona Breast Cancer Summit slide — Erin Cobain, SWOG 2206: Neoadjuvant chemoimmunotherapy in ER+/HER2- selected by MammaPrint2026 Kona Breast Cancer Summit slide — Erin Cobain, SWOG 2206: Neoadjuvant chemoimmunotherapy in ER+/HER2- selected by MammaPrint2026 Kona Breast Cancer Summit slide — Erin Cobain, SWOG 2206: Neoadjuvant chemoimmunotherapy in ER+/HER2- selected by MammaPrint2026 Kona Breast Cancer Summit slide — Erin Cobain, SWOG 2206: Neoadjuvant chemoimmunotherapy in ER+/HER2- selected by MammaPrint
[Slide 1] A Potential Role for Neoadjuvant Chemo-Immunotherapy in HR-Positive, Early-Stage Breast Cancer Surgery 100 90 Investigator's - I 50 Weekly Paclitaxel 12 Adramycin/Cyclophosphamide G2W or GIV) Choice ET Macebo Arm HR+ HER2- Invasive 70 Ductal Carcinoma Pembrolizumab Q3W Pembro Q3W 9 T1c-T2. cN1-cN2 OR 1:1 Randomization 8 I POR. 60 KEYNOTE-756 A 8.5 (4.2-12.8)* 50 P=0.00005 40 T3-T4. cN0-cN2 Investigator's ! 24.3% AND Weekly Pacitaxel X 12 Choice ET 50 Atriamyoin/Cyolophosphamide (G/W or QTW) 15.6% Grade 3 Placebo Q3W Placebo Q3W x9 R 154/835 10 100/643 Cardoso et al. ESMO. 2023. 0 ypTarTis YPNO Surgery 50 i Investigator's : 40 Weekly Paclitaxe X 12 Adiamycin/Cyrclophosphamide - G(W) Choice ET FURNEY HR+ HER2- BC REAST T1c-T2/cN1-cN2 Nivolumab Q2W or Q3W Nivo Q3W 9 Checkmate7FL OR CANCER T3-T4, or cN0-cN2 1:1 Randomization AND pca to less) # 30 20 grade 3 or grade 2 Investigator's - 2026 I 10 24.5 with ER 1-10% Weekly Packtaxel 12 Adnamyon/Cyciophosphamade g/w or G(W) Choice ET 13.8 Placebo Q2W or Q3W Placebo Q3W , 0 Loi et al. ESMO. 2023. miTT --- [Slide 2] MammaPrint High 2 and Neoadjuvant Immunotherapy I-SPY2 trials demonstrated improved rates of pCR when immune checkpoint inhibitors were administered as a component of neoadjuvant systemic therapy in MP High 2 tumors pCR% in NACT (control) versus 10 containing arms MP High 1 MP High 2 Immunotherapy (IO) arm NACT 10 A NACT 10 A Pembrolizumab 13% 18% 5% 21% 61% 40% Pembrolizumab SD-101 10% 17% 7% 21% 45% 24% Durvalumab Olaparib 9% 10% 1% 22% 66% 44% TEMMIT ON BREAST CANCER 2026 HAWAII Nanda et al., JAMA Oncol, 2020; Wolf et al., Cancer Res, 2022; Pusztai et al., Cancer Cell 2021 --- [Slide 3] 70-gene MammaPrint Test: Implications for CT and ET Decisions HIGH RISK LOW RISK -1 0 1 -1.0 -0.8 0.57 0.4 -0.2 0.0 +0.2 +0.355 +0.6 +0.8 +1.0 HIGH 2 (H2) HIGH 1 (H1) LOW ULTRALOW -1.000 to -0.570 0.569 to 0.000 +0.001 to +0.355 +0.356 to +1.000 NEO(ADJUVANT) CT BENEFIT NO NEO(ADJUVANT) CT BENEFIT ET BENEFIT 0-5 YEARS SOME WITH INCREASED SENSITIVITY NO INCREASED EXTENDED ET ET BENEFIT <5 YEARS SUMMIT ON TO IMMUNOTHERARPY, SENSITIVITY TO BENEFIT UP TO 10 BREAST PARP INHIBITOR, IMMUNOTHERARPY, PARP YEARS PLATINUM INHIBITOR, PLATINUM CANCER 2026 MINDACT 170-1, CHAWAII Knauer, NBRST, STO-3,1-SPY2 Knauer, NBRST STO-3,1-SPY2 NAME 842. IDEAL MINDACT STO-3 References: Knauer (Breast Cancer Res Treat 2010), NBRST (Whitworth, Am Surg Oncol 2022), STO-3 (van't Veer, Breast Cancer Res Treat, 2017, Esserman, JAMA Onc 2017), I-SPY2 (https: lwww. ispytrials orgli-spy-platform/l-spy2 Pusztal, Cancer Cell 2021). MINDACT (Piccart, Lancet Oncol, 2021; Lopes Cardozo, JCO, 2022). NSABP-842 (Rastogi, ASCO 2021), A IDEAL (Liefers, SABCS 2022) --- [Slide 4] Clinical Stage II-III Hormone Receptor Positive, HER2-Negative SWOG S2206 Schema Breast Cancer W Patients Consent to MammaPrint Testing, SOC MammaPrint Testing Available and High 2 (score -0.57 to -1) Discussion of Potential Participation in the Trial Physician and Patient Discuss Randomization STEP 1 Registration (Screening) and W MammaPrint Testing STEP 1 Registration Study Chairs: MammaPrint High 2 MammaPrint High 1 Erin Cobain, MD (score -0.57 to -1) or Low Risk Lajos Pusztai, MD, D Phil ......... Primary objective: IDFS STEP 2: Randomization Not Eligible for Study 4TH SUMMIT ON S Secondary objectives: BREAST - pCR 1:1 CANCER - QoL Arm 1: SOC Chemotherapy (AC-T) Arm 2: SOC Chemotherapy (AC-T) + Durvalumab 2026 HAWAII DAVAOncology BREAST CANCER SOC Surgery, Radiation (if indicated), Endocrine Therapy (+/- Targeted Therapy) Follow Up Period: 10 years
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Advanced HER2+ Breast Cancer

Moderator · Milana Dolezal
AM4 of 8 with slides

Coming up at #DAVABreast: Advanced HER2+ Breast Cancer, moderated by Dr. Milana Dolezal @StanfordMed. Looking forward to a focused discussion on the rapidly evolving treatment landscape and emerging strategies across HER2+ disease.

2026 Kona Breast Cancer Summit — Advanced HER2+ Breast Cancer session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Panel on advances on HER2+ve MBC #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Advanced HER2+ Breast Cancer session
VVinay Jain@VinayJaink9vh2026-08-20Source post on X ↗
First line T-DXd for newly diagnosed HER2+ MBC (DESTINY-Breast09)Amina Chaudhry

Dr. @AminaChaudhryMD @StanfordMed: In 1L HER2+ mBC, DESTINY-Breast09 showed longer PFS with T-DXd+P vs THP; 53% achieved CR/deep PR. The discussion highlighted treatment duration, induction/maintenance, sequencing and biomarker-guided personalization. #DAVABreast

DESTINY-Breast09profile
2026 Kona Breast Cancer Summit slide — Amina Chaudhry, First line T-DXd for newly diagnosed HER2+ MBC (DESTINY-Breast09)2026 Kona Breast Cancer Summit slide — Amina Chaudhry, First line T-DXd for newly diagnosed HER2+ MBC (DESTINY-Breast09)2026 Kona Breast Cancer Summit slide — Amina Chaudhry, First line T-DXd for newly diagnosed HER2+ MBC (DESTINY-Breast09)2026 Kona Breast Cancer Summit slide — Amina Chaudhry, First line T-DXd for newly diagnosed HER2+ MBC (DESTINY-Breast09)
[Slide 4] Kaplan-Meier / survival curve — table and text data only
DESTINY-Breast 09: TDX-d + Pertuzumab prolongs PFS compared to THP in First Line HER2+ Metastatic breast cancer A Progression-free Survival Median Progression-free Survival Trastuzumab deruxtecan+ Patients pertuzumab Percentage of Patients Trastuzumab Deruxtecan+ Pertuzumab THP THP Hazard ratio for disease progression or death, 0.56 P<0.00001 (prespecified P-value boundary for SUMMIT ON superiority, 0.00043) BREAST CANCER Month No. at Risk Trastuzumab HAWAII deruxtecan+ pertuzumab THP Initial treatment with T-DXd and pertuzumab showed 13.8 mo improvement in PFS compared with standard THP (28.8 mo vs 18.7 mo) Tolaney S et al. NEJM 2026 Feb 5 DB09 outcomes shared at ASCO 2025 Don't know about T-DXd alone, still waiting for the results of that arm
[Slide 1] Stanford Key Studies Informing First-line Selection Three ongoing studies informing first line selection and sequencing SAPPHO DEMETHER DB-GUIDE De novo HER2+ MBC HER2+ unresectable / MBC HR+/HER2+ MBC Sequential, non-cross-resistant Short T-DXd induction T-DXd + pertuzumab induction HER2-directed therapy THP + T-DXd + T-DM1 + tucatinib T-DXd x 6 cycles T-DXd + P X 18-24 cycles + PHESGO maintenance SUMMIT ON + HP + tucatinib + HP + ET + palbociclib BREAST + T-DXd retreatment CANCER 2026 HAWAII Can treatment intensification Can we limit T-DXd exposure Can we optimize sequencing lead to durable disease control? white maintaining efficacy? and preserve T-DXd for later? How do we balance the remarkable benefit with long-term treatment burden? --- [Slide 2] DESTINY-Breast09 Response characteristics: T-DXd + P arm CR Deep PR* PR (<80%) SD/PD (n=58) (n=141) (n=127) (n=51) Time to best response 8.4 [5.6. 11.1] 9.6 [6.8. 11.0] 1.5 [1.4. 2.0] NA (median, mo) [95% CI] Duration of best response NC [35.1, NC] 39.2 [35.3, NC] 34 8 [22.8, NC] NA (median, mo) [95% CI] 80% of patients (ITT) Patients remaining in best response, % [95% CI] achieved maximal 12 mo 94.8 [84.8, 98.3] 91.3 [85.1, 95.0] 78 9 [70.1, 85.3] NA tumor reduction by 24 mo 85.0 [72.1, 92.3] 78.9 [70.4, 85 2] 60 4 [50.0, 69.3] NA 24 months Total treatment duration, (median, mo) [range]b 28 0 [4 8-44 5] 25 4 [3.4-42.7] 20 6 [2 8-41 8] 4.4 [0.3-37.2] SUMMET ON BREAST PFS at 24 mo, % [95% CI] 85. 1 [72 2, 92.3] 80.0 [71.7. 86.1] 64 3 [54.3, 72.8] 35 5 [21.1, 50.2] CANCER 2026 HAWAII Importantly, median time to best response was 8.4 mo for CR and 9.6 mo for deep PR At 2 years, over 80% of patients were free from progression or death, so even a deep partial response prognostically holds a very favorable meaning The shrinkage of the disease didn't just occur initially, but it deepened over time You can see that the nadir, the maximum shrinkage of disease was approximately at 1 year Park YH, et al. ASCO 2026. Abstract 1021 --- [Slide 3] Among 377 patients that received T- DXd +P in DB-09 00 Response Categories Over half of patients (n=377) (53%) achieved CR or Deep PR SD/PD CR 13.5% 15.4% PR (<80%) SUMMIT OK BREAST 33.7% Deep PR (≥80%)* CANCER 37.4% a 2026 HAWAII Park YH, et al. ASCO 2026. Abstract 1021.
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
T-DXd rechallenge and mitigation of ILDKelsey Natsuhara
Tucatinib + T-DM1: Updated data from the HER2CLIMB-02 trialAlison Conlin

Dr. @AliConlinMD @providence : In HER2CLIMB-02, adding tucatinib to T-DM1 improved PFS in HER2+ mBC (9.5 vs 7.4 mo) and in patients with CNS disease (7.8 vs 5.7 mo), but not OS, with added GI toxicity including elevated LFTs and diarrhea. #DAVABreast

HER2CLIMB-02profile
2026 Kona Breast Cancer Summit slide — Alison Conlin, Tucatinib + T-DM1: Updated data from the HER2CLIMB-02 trial2026 Kona Breast Cancer Summit slide — Alison Conlin, Tucatinib + T-DM1: Updated data from the HER2CLIMB-02 trial2026 Kona Breast Cancer Summit slide — Alison Conlin, Tucatinib + T-DM1: Updated data from the HER2CLIMB-02 trial2026 Kona Breast Cancer Summit slide — Alison Conlin, Tucatinib + T-DM1: Updated data from the HER2CLIMB-02 trial
[Slide 2] Kaplan-Meier / survival curve — table and text data only
HER2CLIMB02: Overall Survival T-DM1 tucatinib T-DM1 placebo Patients who have discontinued or never received study treatment, n (%) Patients who received 21 subsequent anticancer systemic therapy (%)* Median subsequent lines of therapies (range) Subsequent therapies, n (%)* T-DXd Chemotherapy' Trastuzumab Tucatinib Events Median os (95% a) T-DM1 tucatinib give FUMMIT ON BREAST T-DM1 placebo CANCER 38.0 months (31.5-NR) os Probability (%) DAVADrestagy HAWAII T-DM1 tucatinib T-DM1 + placebo Time From Randomization, Months Patients at risk T-DM1 Tucatinib T-DM1 Placebo Hurvitz et al, Ann of Onc, March 2026
[Slide 3] Kaplan-Meier / survival curve — table and text data only
HER2CLIMB02 PFS in CNS Patients Events Median PFS (95% CI) T-DM1 tucatinib 7.8 months (6.7-10.0) 5.7 months (4.6-7.5) PFS Probability (%) T-DM1 placebo SIGNATURE ON BREAST T-DM1 + tucatinib CANCER T-DM1 + placebo HAWAII Time From Randomization, Months Patients at risk T-DM1 Tucatinib 99 T-DM1 Placebo 105 Hurvitz et al, Ann of Onc, March 2026
[Slide 4] Kaplan-Meier / survival curve — table and text data only
HER2CLIMB02 Progression Free Survival Events Median PFS (95% a) T-DM1 tucatinib 9.5 months (7.4-10.9) T-DM1 placebo 7.4 months (5.6-8.1) PFS Probability (%) SUMMET ON BREAST T-DM1 + tucatinib CANCER T-DM1 placebo HAWAII Time From Randomization, Months Patients at risk T-DM1 Tucatinib T-DM1 Placebo ISD Hurvitz et al, Ann of Onc, March 2026
[Slide 1] HER2CLIMB02: Most Common TEAEs 100 90 Grade 1-2 Grade >3 T-DM1 Tucatinib 80 T-DM1 Placebo 70 3.5 Percentage (%) 60 2.1 4.8 50 6.1 40 3.0 0.9 17 1.3 0.4 0.9 0.4 30 61.9 0.9 51.9 16.5 0.9 2.1 "SUMMIT ON 47.3 16.5 38.2 09 0.9 0.4 BREAST 20 42.8 26 0.4 34.3 35.1 2.1 2.6 34.6 33.8 32.9 32.6 0 CANCER 25.7 10 18.1 21.8 25.9 15.1 19.4 19.3 22.9 23.0 24.9 16.7 14.6 14.6 2026 HAWAII 0 Nausea \ Faligue Vomiting AST increased ALT increased Headache Epistaxis Decreased appetito Constipation Pyrexia Anthralgia Most common (>5%) grade ≥3 TEAEs (T-DM1 + tucatinib vs T-DM1 + placebo): ALT increased (16.5% vs 2.6%), AST increased (16.5% vs 2.6%), anemia (8.2% vs 4.7%), thrombocytopenia (7.4% vs 2.1%), and fatigue (6.1% vs 3.0%) Hurvitz et al, Ann of Onc, March 2026
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
HER2-CLIMB 05: Tucatinib maintenanceMary Kathryn Pitner
EmpowHER 303: zanidatamab in metastatic HER2+ breast cancerMark Pegram
EmpowHER 303
ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial designMarko Velimirovic

Dr. @marko_velimir @fredhutch presents a phase II chemotherapy-sparing strategy for HR+/HER2+ advanced breast cancer using ET + CDK4/6i + trastuzumab + HER2 TKI, with FES PET selection and 3-week ctDNA response assessment. #DAVABreast

PATINAprofile
2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design
[Slide 4] Kaplan-Meier / survival curve — table and text data only
Chemotherapy-sparing regimen in HR+/HER2+ mBC? PERTAIN study Trastuzumab Pertuzumab Plus Trastuzumab Trastuzumab Arm Arm Events, No. (%) Median PFS. months Trastuzumab A. months Event-Free Probability (%) Pertuzumab Median JUMMIT ON BREAST CANCER HAWAII Pertuzumab plus trastuzumab arm Trastuzumab arm Progression-Free Survival (months) No. risk Pertuzumab plus trastuzumab arm Trastuzumab arm Rimawi et al, JCO 2018
[Slide 1] Key outcomes Delay the use of chemotherapy and ADCs in selected patients with luminal HR+/HER2+ advanced breast cancer by leveraging highly effective therapies targeting both ER and HER2 signaling Improve tolerability, reduce treatment-related toxicities BREAST CANCER 2026 HAWAII Validate clinical utility of FES PET as a biomarker of response to endocrine therapy in HR+/HER2+ advanced breast cancer --- [Slide 2] Study design Phase II, single-arm study HR+/HER2+ ADVANCED BREAST CANCER KEY ELIGIBILITY CRITERIA SCREENING LEAD-IN TREATMENT EARLY MOLECULAR RESPONSE PRIMARY ENDPOINT ER+ (>10%) Landmark PFS AT 3 WEEKS FES-PET-positive (SUVmax >1.8 in >80% lesions) CONTINUE SECONDARY ENDPOINTS HER2+ (IHC 3+ or 2+ and amplified by ISH) FESPET ctDNA stable or TREATMENT PROs/QoL De novo unresectable, locally advanced or ET (AI/SERD) decreasing UNTIL PROGRESSION Time to chemotherapy/ADC metastatic disease CDK4/6i OS If recurrent, >1 year of completion of curative Trastuzumab BRAIN MRI ORR, CBR, DOR SUMMIT ON therapy for early-stage primary breast cancer HER2 TKI ctDNA rising OFF STUDY BREAST CNS-PFS (RANO-BM) Measurable disease per RECIST v1.1 CANCER Molecular response to therapy CNS involvement at baseline is allowed if Response to subsequent lines 2026 asymptomatic or treated BASELINE ctDNA of therapy HAWAII ECOG PS <3 Anticipated landmark PFS at 24 months >50% --- [Slide 3] Background: [18F] FES PET Predicting response to endocrine 8.00 therapy beyond ER% staining from a single site tissue biopsy Heterogeneous vs homogeneous FES uptake - median PFS in the heterogeneous VS. homogeneous FES uptake in HR+ BREAST CANCER metastatic breast cancer: 5.5 VS. 21.6 0.00 months, HR 5.4, p < 0.001 2026 HAWAI DAVAOres/ogy FES PET strongly predictive of PFS using a threshold of SUVmax > 1.8 Estrogen Receptor- targeted imaging Linden et al, ASCO 2025
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Dr. @marko_velimir @fredhutch presents a phase II chemotherapy-sparing strategy for HR+/HER2+ advanced breast cancer using ET + CDK4/6i + trastuzumab + HER2 TKI, with FES PET selection and 3-week ctDNA response assessment. #DAVABreast

PATINAprofile
2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design2026 Kona Breast Cancer Summit slide — Marko Velimirovic, ER+/PR+/HER2 triple+ MBC: Update from PATINA and new trial design
[Slide 4] Kaplan-Meier / survival curve — table and text data only
Chemotherapy-sparing regimen in HR+/HER2+ mBC? PERTAIN study Trastuzumab Pertuzumab Plus Trastuzumab Trastuzumab Arm Arm Events, No. (%) Median PFS. months Trastuzumab A. months Event-Free Probability (%) Pertuzumab Median JUMMIT ON BREAST CANCER HAWAII Pertuzumab plus trastuzumab arm Trastuzumab arm Progression-Free Survival (months) No. risk Pertuzumab plus trastuzumab arm Trastuzumab arm Rimawi et al, JCO 2018
[Slide 1] Key outcomes Delay the use of chemotherapy and ADCs in selected patients with luminal HR+/HER2+ advanced breast cancer by leveraging highly effective therapies targeting both ER and HER2 signaling Improve tolerability, reduce treatment-related toxicities BREAST CANCER 2026 HAWAII Validate clinical utility of FES PET as a biomarker of response to endocrine therapy in HR+/HER2+ advanced breast cancer --- [Slide 2] Study design Phase II, single-arm study HR+/HER2+ ADVANCED BREAST CANCER KEY ELIGIBILITY CRITERIA SCREENING LEAD-IN TREATMENT EARLY MOLECULAR RESPONSE PRIMARY ENDPOINT ER+ (>10%) Landmark PFS AT 3 WEEKS FES-PET-positive (SUVmax >1.8 in >80% lesions) CONTINUE SECONDARY ENDPOINTS HER2+ (IHC 3+ or 2+ and amplified by ISH) FESPET ctDNA stable or TREATMENT PROs/QoL De novo unresectable, locally advanced or ET (AI/SERD) decreasing UNTIL PROGRESSION Time to chemotherapy/ADC metastatic disease CDK4/6i OS If recurrent, >1 year of completion of curative Trastuzumab BRAIN MRI ORR, CBR, DOR SUMMIT ON therapy for early-stage primary breast cancer HER2 TKI ctDNA rising OFF STUDY BREAST CNS-PFS (RANO-BM) Measurable disease per RECIST v1.1 CANCER Molecular response to therapy CNS involvement at baseline is allowed if Response to subsequent lines 2026 asymptomatic or treated BASELINE ctDNA of therapy HAWAII ECOG PS <3 Anticipated landmark PFS at 24 months >50% --- [Slide 3] Background: [18F] FES PET Predicting response to endocrine 8.00 therapy beyond ER% staining from a single site tissue biopsy Heterogeneous vs homogeneous FES uptake - median PFS in the heterogeneous VS. homogeneous FES uptake in HR+ BREAST CANCER metastatic breast cancer: 5.5 VS. 21.6 0.00 months, HR 5.4, p < 0.001 2026 HAWAI DAVAOres/ogy FES PET strongly predictive of PFS using a threshold of SUVmax > 1.8 Estrogen Receptor- targeted imaging Linden et al, ASCO 2025
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
Curative-intent SBRT + surgery for de novo HER2+ with up to five sitesShane Stecklein
De-escalating dose or fewer drugs in older patients with HER2+ BCYelena Novik

Dr. Yelena Novik of @nyulangone reviews escalation/de-escalation in early HER2+ breast cancer, including chemotherapy-sparing approaches and the potential role of imaging, ctDNA dynamics and HER2DX in guiding treatment. #DAVABreast

2026 Kona Breast Cancer Summit slide — Yelena Novik, De-escalating dose or fewer drugs in older patients with HER2+ BC2026 Kona Breast Cancer Summit slide — Yelena Novik, De-escalating dose or fewer drugs in older patients with HER2+ BC2026 Kona Breast Cancer Summit slide — Yelena Novik, De-escalating dose or fewer drugs in older patients with HER2+ BC2026 Kona Breast Cancer Summit slide — Yelena Novik, De-escalating dose or fewer drugs in older patients with HER2+ BC
[Slide 1] GUIDING THERAPY De escalation: omit toxic chemotherapy : anthracycline, platinum Escalate/ innovate DB 11/DB 05 Guide de scalation Imaging ( Phergain) ON BREAST Ct DNA CANCER 2026 Her DX HAWAII BAVACHESANDY ****** --- [Slide 2] DE ESCALATE: ********* Japanese trial RESPECT enrolled women aged 70-80 years with stage I-IIIA HER2+ Patients were randomly assigned to receive adjuvant T monotherapy or T plus chemotherapy. 275 patients with a mean age of 73.5 years, mean follow-up of 4.1 years. Non inferiority for Tmonotherapy was not met; however, the difference in 3-year restricted mean survival time between arms was less than 1 month. SUMMIT BREAST CANCER The 3-year RFS was 92.4% (95% CI, 86.3-95.8) with T versus 95.3% (89.7-97.8) with Tplus 2026 chemotherapy. T HAWAII he 3-year OS was 97.2% (91.2-99.1) in the monotherapy group and 96.6% (89.5-98.9) in the combination group. The toxicity profile and health-related quality of life outcomes favored trastuzumab monotherapy, supporting its potential use in selected older patients. --- [Slide 3] a) 8 a) HOW TO GUIDE THERAPY a a) a) CHOICES a) of Her 2 DX : genomic assay validated ctDNA dynamics 75% relative reduction achieved after 2 cycles et Ct DNA clearance strong correlation with pcr SUMMET ON BREAST CANCER 2026 HAWAII --- [Slide 4] PHERGAIN DE PET-guided, response-adapted approach using dual HER2 blockade ESCALATE ??? 356 patients with HER2-positive, stage I-IIIA, operable invasive breast cancer (tumor size ≥1.5 cm and at least one PET- NO CHEMO evaluable lesion) were randomly assigned in a 1:4 ratio. Group A received standard neoadjuvant therapy TCHP Group B received HP plus endocrine therapy (ET). Treatment in Group B was guided by FDG-PET response after two cycles and by pCR)at surgery. "SUMMET ON Patients without a PET response or without a pCR were BREAST escalated to CT. The PET-guided, pCR-adapted approach CANCER demonstrated a strong 3-year iDFS rate of 94.8% in Group B. 2026 HAWAII median follow-up of 5.6 years, the 5-year iDFS rate was 89.5% in Group B overall and 92.4% among patients who did not receive CT. Chemotherapy was omitted in approximately one- third of patients and delayed in others based on response.
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Novel ADCs: Session I

Moderator · Dennis Slamon
AM5 of 6 with slides

Starting soon: Novel ADCs: Session I, moderated by Dr. Dennis Slamon @dgsomucla. A focused look at emerging antibody–drug conjugates, novel targets and payloads, and how the next generation of ADCs may reshape breast cancer treatment. #DAVABreast

2026 Kona Breast Cancer Summit — Novel ADCs: Session I session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Panel on novel ADCs #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Novel ADCs: Session I session
[Slide 1] & & & & & & DAVAOncology facilitating successful drug development facilitating DAVAOncology successful drug development focilitating DAVAOncology successful drug development & 8 KONA BREAST CANCER SUMMIT in B & DAVA Oncology duvoonc.com & 8 BREAST 8 CANCER 2026 HAWAN MODERATOR & 8 of & DAVAOncology Justitufing DAVAOncology successful drug development DAVAOncology - drug Gratumer successful drug development DIVAOnalog cology ology & 8 DAVAOnat for DAVAOncology DAVAOncology™ AVA DAVIOcology DAVAOsology DAVADocology DAVAOraskogy DAVAOncology DAVAOscology Mecory DAV&ONOOGY DAVAOncology DIAOnodogy
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Dato-DXd with or without immunotherapy vs chemoimmunotherapyPriyanka Sharma

Dr. Priyanka Sharma @KUMedCenter on evolving ADC strategies in TNBC: • TROPION-Breast02: Dato-DXd PFS 10.8 vs 5.6 mo; OS 23.7 vs 18.7 mo vs chemo • ASCENT-04: SG + pembro PFS 11.2 vs 7.8 mo vs chemo + pembro in PD-L1+ TNBC • BEGONIA Arm 7: Dato-DXd + durvalumab showed mPFS 13.8 mo in 1L unresectable locally a/m TNBC • I-SPY2.2: Dato-DXd + durvalumab achieved 43% pCR in TNBC, with activity enriched in the immune+ subtype • Phase III trials are testing whether ADC + IO can replace or reduce conventional polychemotherapy + IO in early-stage TNBC #DAVABreast

ASCENT-04I-SPY2TROPION-Breast02
2026 Kona Breast Cancer Summit slide — Priyanka Sharma, Dato-DXd with or without immunotherapy vs chemoimmunotherapy2026 Kona Breast Cancer Summit slide — Priyanka Sharma, Dato-DXd with or without immunotherapy vs chemoimmunotherapy2026 Kona Breast Cancer Summit slide — Priyanka Sharma, Dato-DXd with or without immunotherapy vs chemoimmunotherapy2026 Kona Breast Cancer Summit slide — Priyanka Sharma, Dato-DXd with or without immunotherapy vs chemoimmunotherapy
[Slide 3] Kaplan-Meier / survival curve — table and text data only
ASCENT-04/KEYNOTE-D19 SG + Pembro* Previously untreated, inoperable, locally advanced, or metastatic TNBC SG: 10 mg/kg IV on d 1 and 8 of 21-d cycles Pembro: 200 mg IV on di 1 of 21-d cycles Treated until PD-L1+ (CPS >10, IHC 22C3 assay) BICR-verified disease Long-term >6 months since treatment in the curative setting progression or follow-up Prior anti-PD-(L)1 agent allowed in the curative setting Physician's Choice of Chemotherapy unacceptable toxicity PD-L1 and TNBC status centrally confirmed Pembro Primary endpoint: PFS by BICR per RECIST v1.1 Stratified by geographic location (US/Canada/Western Europe vs rest of world), Secondary endpoints: OS, ORR, DOR by BICR, safety, QOL de nove vs recurrent disease within 6-12 months from completion of treatment in the curative setting vs recurrent disease >12 months from completion of DO Penders treatment in the curative setting and prior exposure to anti-PO-(L)-1 theropy Number PFS events Median PFS, mo (95% CI) treatfied - (PSN (1) same -month PES note, N (95% C) 12 month PFS 195% 08 - SUMMIT ON Pregression I 2 Overat E I BREAST CANCER so Pembro Chemo Pembre Number of 05 events Median os, me 195% 0) HAWAII No. risk Time (months) No. at risk Time (months) 10 Fembre 50 Pembre Cheme Fembre Chemo Pembro Cross over allowed : apx 80% of patients from Chemo arm crossed over to SG upon progression Tolaney SM, et at ASCO2025 Presentation LBA109
[Slide 4] Kaplan-Meier / survival curve — table and text data only
Number atrisk
Dato-DXd323265191150116845641242010510
ICC3211911076446291916861000
TROPION-Breast02: PFS by BICR Dato-DXd ICC 12-mo rate: PFS events, n (%) 18-mo rate: P value Probability of PFS Median PFS (95% CI) BREAST ORR: 62% vs 29% CANCER Number at risk Time from randomization (months) Dato-DXd HAWAII ICC Dato-DXd demonstrated a statistically significant and clinically meaningful improvement in PFS compared with ICC, reducing the risk of progression or death by 43% Dent RA, et al. ESMO 2025 1BA21
[Slide 1] Rates of pCR after datopotamab deruxtecan (Dato) plus durvalumab: Results from the I-SPY2.2 trial EARLY ESCALATION EARLY ESCALATION AFTV AFTV O 0.0 DATO-DxD + Durva 0-0-0 Taxol t Carbo + PD1i AC + PD1i O N=106 64 25 25 Screen Randomize preRCB premicis Surgery Block A Block B Block C All patients must screen Mammaprint High Risk 42 39 to be eligible Surgery Surgery Response Predictive Subtype N pCR non-pCR* Modeled Rate (95% CI) Threshold P(>Thr) 3% HR+Immune-DRD- 25 O 23 15% 0.00 pCR (0%-7%) BREAST 13% HR-Immune-DRD- 23 2 14 15% 0.33 TNBC (n=64)=43% CANCER (3%-23%) 65% Immune+ 47 20 11 40% 0.99 HR+ (n=42)=18% 2026 (47%-83%) HAWAII 24% (includes treatment on Immune-DRD+ 11 3 6 40% 0.06 (4%-44%) Block B/C for some pts) Receptor Subtypes N pCR non-pCR* Modeled Rate (95% CI) Threshold P(>Thr) HR+ 42 4 29 18% 15% 0.68 Graduation (6%-30%) 44% HR- 64 21 25 40% 0.74 threshold for PCR (32%-56%) met only in immune+ subtype Shatsky RA et al. Nature medicine 2024 --- [Slide 2] Datopotamab deruxtecan (Dato-DXd) + durvalumab as first-line treatment for unresectable locally advanced/metastatic TNBC: Updated Arm 7 results from phase Ib/II BEGONIA study congress ESMO Study Design BEGONIA Arm 7: Dato-DXd + Durvalumab Eligibility criteria Treatment arms Part f Part expansion aged Antitumour Responses in 1L a/mTNBC Median PFS: 13.8 months 10th Freor Confirmed ORR was 79% (49/62; 95% CI, 66.8-88.3) with 6 CR and 43 PR Arm Date-OX# mg/kg | organ D I patients 100 Antitumour responses were observed regardless of PD-L1 expression level as OTW PO assessed by 2 separate PD-L1 assays and scoring methods 50 ON - - TOPO PER Characteristic N=62 Best change from baseline lession 0 Dato-DXd D Age, median (range), years 53 (31-74) -50 SUMMIT ON No prior treatment n (%) 26 (42) M High BREAST Low Prior treatments for early-stage disease, n (%) 100 # CANCER Radiotherapy 30 (48) Cytotoxic chemotherapy 33 (53) PD-L1 expression SP263 PD-L1 TAP 10% cutoff 2026 22C3 PD-L1 CPS 10 cutoff HAWAII Taxane 26 (42) DAYA Dreslogy - Anthracycline 29 (47) Progressive disease Stable onease Not evaluate Partial response Complete response Platinum compound 9 (15) - " Hormonal therapy 10 (16) - - Targeted therapy 1 (2) - area importe Data Feb 2023 Visceral metastases, (%) 37 (60) Lymph node metastases n (%) 42 (68) PD-L1 expression, n (%) High (TAP >10%) (11) Low (TAP <10%) 54 (87) Unknown/Missing 1 (2) Schmid P et of ESMO 2023, Abstract # 379MO
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ADCs in breast cancer: biomarker requirements and balancing efficacy and toxicityShou-Ching Tang
Ongoing trials with sacituzumab tirumotecan in TNBC and HR+/HER2- BCAdam Brufsky

Dr. Adam Brufsky (@breastoncdoc) @UPMCHillmanCC on future TROP2 ADCs: Sac-TMT trials, ADC+ICI activity in PD-L1–negative TNBC, TROP2/TOP1-mediated resistance, and potential cross-resistance with sequential topo-I ADCs are informing future combination and sequencing strategies. #DAVABreast

2026 Kona Breast Cancer Summit slide — Adam Brufsky, Ongoing trials with sacituzumab tirumotecan in TNBC and HR+/HER2- BC2026 Kona Breast Cancer Summit slide — Adam Brufsky, Ongoing trials with sacituzumab tirumotecan in TNBC and HR+/HER2- BC2026 Kona Breast Cancer Summit slide — Adam Brufsky, Ongoing trials with sacituzumab tirumotecan in TNBC and HR+/HER2- BC2026 Kona Breast Cancer Summit slide — Adam Brufsky, Ongoing trials with sacituzumab tirumotecan in TNBC and HR+/HER2- BC
[Slide 4] Kaplan-Meier / survival curve — table and text data only
All patients (N 41)
PFS events, n (%)20 (48.8)
Median PFS, months (95% CI)13.4 (9.9, 18.2)
12-month PFS rate (95% CI), %64.6 (45.0, 78.7)
Progression-Free Survival PFS benefits were observed regardless of PD-L1 expression. All patients PD-L1 CPS <10 PFS events, n (%) PFS events, n (%) Median PFS, months (95% CI) Median PFS, months (95% CI) 12-month PFS rate (95% CI), % 12-month PFS rate (95% CI). % Progression Free Survival (%) Progression Free Survival (%) mPFS: 13.1 mo mPFS: 13.4 mo SUMMIT ON BREAST Censer Censor Sac-TMT Sac-TMT CANCER Time in Months Time in Months HAWAII Number of subjects at risk (Events) Number of subjects at risk (Events) Sac-TMT Sac-TMT 2025 ASCO #ASCO25 FRE SENTED BY Professor Yongmei Yin ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reune, contact permissions@as.org KNOWLEDGE CONQUERS CANCER
[Slide 1] Retrospective Data About Sequential Use of Topo1i ADCs HR+/HER2-low MBC (n=56) HR-/HER2-low MBC (n=28) ADC1 (SG) IntTx ADC2 (T-DXd) ADC1 (SG) Intix ADC2 (T-DXd) A. 23 C. 25-1 1 IntTx 1 23- IntTx 1 21- 19- InfTx 2 21- IntTx 2 19- SG T-DXd Participants 17- 15- IntTx 3 Participants 17- X Toxicity 15- 13- X Toxicity 13- 11- 9- Still on Therapy 11- 10 7- 7- 5- 5- 3- 3- 1- 20 10 0 10 20 10 20 20 10 0 10 20 10 20 (n=24, 42.9%) Time on treatment (months) (n=25, 89.3%) Time on treatment (months) DUMMIT ON BREAST B. ADC1 (T-DXd) IntTx ADC2 (SG) D. ADC1 (T-DXd) InfTx ADC2 (SG) CANCER IntTx 1 34 IntTx 2 T-DXd SG Participants IntTx 1 Participants 1- 2026 HAWAII IntTx 3 20 10 o 10 20 10 20 CARDER 17- X 15- Toxicity Time on treatment (months) . Still on Therapy 9- 20 10 0 10 20 10 20 (n=32, 57.1%) Time on treatment (months) (n=3, 10.7%) Huppert LA et al. NPJ Breast Cancer. 2025;11(1):34. --- [Slide 2] Implications of Resistance Mechanisms for ADC Sequencing PreWildstypent TOP1 E418KK TACSTD2/TROP2 T256R TROP2-targeted Sacituzumab ADC Govitecan No Response TROP2 T256R TROP2 mutation TROP2 #: Intracefular B Non-TROP2- Response targeted ADC SN TOPI E418K TOP1 Endosome TOP1i payload ADC BREAST No Response CANCER N TOP1 mutation 2026 CHAWAII TOP1 Inhibition Altered TROP2 Localization & Non-TOP11- Failed SN38/TOP1 Binding Response dsDNA breaks Binding payload ADC ADC, antibody-drug conjugate; TACSTD2, tumor associated calcium signal transducer 2: TOP1i, topoisomerase I inhibitor; TROP2, trophoblast cell-surface antigen 2. Coates JT, et al. Cancer Discov. 2021;11(10):2436-2445 --- [Slide 3] ********* ......... / ........ Is There a Role for ICI in PDL1-Neg When Combined With ADC? ********* ********* / DIAMOND (Ph 2): Dato-DXd plus durvalumab in 1st line mTNBC (87% PDL1-negative) Dato-DXd +/- durvalumab in PD-L1- mTNBC Median PFS 13.8 months Median 100 DoR 15.5 months Previously untreated, Dato-DXd / locally advanced Objective Response rate 79% 50 inoperable or BREAST change beseine form Beat lesion torget (%) 5 $ metastatic TNBC 1:1 0 PD-L1- (CPS <10) No prior neoadj/adj IO N=140 -50 # within 6 mo CANCER H High 1. Low Dato-DXd + 2026 HAWAII -100 U Unknown/Missing # Stratification Factors: DAVACreshogy durvalumab ession De novo OR DFI≤12 mo OR PD-L1 SP263 PD-L1 TAP 10% cutoff DFI>12 mo 22C3 PD-L1 CPS 10 cutoff Progressive disease Stable disease Not natuable Partix response Complete response NCT06954480 PI Peter Schmid ...... Schmid P et al. ESMO Virtual Plenary. Abstract VP1-2025.
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Emiltatug ledadotin (XMT-1660), an anti-B7H4 ADC for HER2-low/negative BCChristos Vaklavas

“In the making of ADCs, get the recipe right.” Dr. Christos Vaklavas @huntsmancancer reviews Phase I/Ib development of XMT-1660 (emiltatug ledadotin), a novel B7-H4–directed dolasynthen ADC, highlighting early clinical activity and a favorable adverse-event profile. #DAVABreast

2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Emiltatug ledadotin (XMT-1660), an anti-B7H4 ADC for HER2-low/negative BC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Emiltatug ledadotin (XMT-1660), an anti-B7H4 ADC for HER2-low/negative BC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Emiltatug ledadotin (XMT-1660), an anti-B7H4 ADC for HER2-low/negative BC2026 Kona Breast Cancer Summit slide — Christos Vaklavas, Emiltatug ledadotin (XMT-1660), an anti-B7H4 ADC for HER2-low/negative BC
[Slide 1] BG-C9074 (B7-H4 targeting ADC) Association between B7-H4 expression & activity. uORR in B7-H4 subgroups in OC uORR in B7-H4 subgroups in TNBC across all dose levels across all dose levels 37-H4 TC< cutoff B7-H4 TC ≥ cutoff 87-H4 TC cutoff B7-H4 TC 2 cutoff 60% 60% 50% 47.8% 50% 46.2% 46.2% 41.2% 42.4% 38.9% 40% 35.7% 40% 37.5% 30% 30% 20% 20% 10% 10% 0.0% 0.0% SUBMIT ON 0% BREAST 0% All comer n=18 n=33 n=28 n=23 All comer n=3 n=13 n=3 n=13 CANCER (B7-H4 evaluable; (B7-H4 evaluable; n=51) 25% cutoff 50% cutoff n=16) 25% cutoff 50% cutoff 2026 HAWAII In OC, responses were observed across all levels of B7-H4 expression In TNBC, most enrolled patients had high B7-H4 expression, and all responses occurred in this subgroup Xu B, of al. First-In-human study of BG-C9074 (B7-H4-targeting ADC) in advanced solid tumors: dose escalation and safety expansion. J Clin Oncol. Volume 43, Number 16_ suppl June 2025 494 --- [Slide 2] XMT-1660 (Emiltatug Ledadotin) Phase I/lb. Adverse Events. Total (N=141) Any treatment related adverse event (TRAE) 117 (83.0%) AST/ALT/ALP increase Grade 3 TRAE 52 (36.9%) 44%/17% (G3) Treatment-related serious adverse event (SAE) 8 (5.7%) TRAE leading to treatment discontinuation 5(3.5%) TRAE leading to dose reduction 23 (16.3%) Pyrexia 11%/1% (G3) TRAE leading to dose delay 33 (23.4%) Proteinuria, 40%/14% (G3) SUMMIT ON TRAE leading to death 0 BREAST CANCER Most common TRAEs were transient AST increase, generally asymptomatic and reversible proteinuria, generally low-grade fatigue and nausea 2026 HAWAII Reasons for discontinuation: proteinuria (G3), infusion related reaction (G3), nephrotic syndrome in the presence of gout flare (G3), cystitis hemorrhagic Anemia 17%/6% (G3) Fatigue, 33% (G2), pain in extremity (G2) Thrombocytopenia 11%/1% (G3) No dose-limiting treatment-related neuropathy, neutropenia, ocular toxicity, ILD, or thrombocytopenia observed in this data set Nausea, 31%,1% (G3) Hamilton EP, et al. Initial phase 1 dose escalation data for emiltatug ledadotin (Emi-Le), a novel B7-H4-directed dolasynthen antibody-drug conjugate. J Clin Oncol. 2025;43(suppl 16):3009. 492 doi:10.1200/JCO.2025.43.16_suppl.3009. --- [Slide 3] XMT-1660 (Emiltatug Ledadotin) What is the Novelty? T-cell exhaustion GlycoConnect: Enzymatic remodeling of a glycan at N297 T-regs Recruitment of TAMs XMT-1660 followed by metal-free click-conjugation of cytotoxic payload Fleximer had OH OH -35 toot 1-2 toot T-cell OH OH'O 8-10 OH O 0-1 OHO HN HN HN HN ? O HN HN N297 HO HN B7-H4 NH NH NH S. O ... OMeO OMe Me HN SUMMIT ON HN BREAST 5 12 0 H2N O 0 COOH CANCER 3-5 Cancer Auristatin F- 2026 HAWAII Cell PD-L1 hydroxypropylamide HPA Tumor Progression Immune Evasion AF AF-HPA Created in https://BioRender.com Bever L, et at Generation of DAR1 Antibody-Drug Conjugates for Ultrapotent Payloads Using Tailored GlycoConnect Technology. Bioconjug Chem 2023 Mar 15;34(3):538-548 doc 10 1021/acs bioconjchem.2c00611 489 Toader D. et at. Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer. Mol Cancer Ther. 2023 Sep 5,22(9)999-1012 doc 10.1158/1535-7163.MCT-22-0786 Yurkovetskiy A, et . Dolaflexin: A Novel Antibody-Drug Conjugate Platform Featuring High Drug Loading and a Controlled Bystander Effect. Mol Cancer Ther 2021 May;20(5):885-895. doc 10.1158/1535-7163.MCT-20-0166 --- [Slide 4] ........ ADCs: Getting the Recipe Right Like a Baklava ......... - BAKLAVA 900 g Life 8202 THINKEAN NEMENT NUMMIT ON BREAST CANCER 2026 HAWAII 1. <1% of an ADC targets the tumor 2. Main disposition of an ADC is from target independent uptake in normal tissues 3. Free payload may reach cytotoxic concentrations in plasma 4. Mechanisms operational in the naked mAb, still relevant to the ADC (with added toxicity from linker- payload) CoSmbo Disconnectbetween prectinical studies and clinical observations Nov 1;14(11):2089-2108. doi: 10.1158/2159-8290.CD-24-0708. Tsao LC. et a Effective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd). Nat Commun 2025 Apr 2;16(1):3167. doi: 10.1038/s41467-025- 58266-8. 488 Pictures shamelessly stolen and without credit from the Internet
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Bulumtatug fuvedotin, an anti-Nectin-4 ADC for breast and other solid tumorsRebecca Shatsky

Dr. Rebecca Shatsky (@Dr_RShatsky) @UCSanDiego reviews bulumtatug fuvedotin (9MW2821), a Nectin-4 ADC with DAR 4, site-specific conjugation and a protease-cleavable MMAE payload, being evaluated in TNBC post–topo-I ADC exposure and across other solid tumors. #DAVABreast

2026 Kona Breast Cancer Summit slide — Rebecca Shatsky, Bulumtatug fuvedotin, an anti-Nectin-4 ADC for breast and other solid tumors2026 Kona Breast Cancer Summit slide — Rebecca Shatsky, Bulumtatug fuvedotin, an anti-Nectin-4 ADC for breast and other solid tumors2026 Kona Breast Cancer Summit slide — Rebecca Shatsky, Bulumtatug fuvedotin, an anti-Nectin-4 ADC for breast and other solid tumors2026 Kona Breast Cancer Summit slide — Rebecca Shatsky, Bulumtatug fuvedotin, an anti-Nectin-4 ADC for breast and other solid tumors
[Slide 1] Bulumtatug Fuvedotin Phase 1/1b in Solid Tumors: Adverse Events Annals of Oncology J. Zhang et al. Table 2. Common (>20%) treatment-related adverse events Preferred term n (%) All patients (N - 274) 1.25mg/kg (N = 254) 1.5 mg/kg (N = 16) All grades Grade 3 All grades >Grade 3 All grades Grade 3 WBC count decreased 152 (55.5) 72 (26.3) 139 (54.7) 66 (26.0) 12 (75.0) 6 (37.5) Neutrophil count decreased 141 (51.5) 85 (31.0) 130 (51.2) 79 (31.1) 10 (62.5) 6 (37.5) Anemia 132 (48.2) 24 (8.8) 121 (47.6) 22 (8.7) 10 (62.5) 2 (12.5) AST increased 131 (47.8) 10 (3.6) 122 (48.0) 9(3.5) 8 (50.0) 1 (6.3) ALT increased 107 (39.1) 7 (2.6) 98 (38.6) 6 (2.4) 8 (50.0) 1 (6.3) Peripheral sensory neuropathy" 104 (38.0) 14 (5.1) 96 (37.8) 13 (5.1) 6.(37.5) 1 (6.3) Asthenia 100 (36.5) 12 (4.4) 91 (35.8) 11 (4.3) 9 (56.3) 1 (6.3) EAST Decreased appetite 94 (34.3) 4 (1.5) 84 (33.1) 4(1.6) 9 (56.3) 0 (0.0) NCER Rash 85 (31.2) 14 (5.1) 79 (31.1) 13 (5.1) 4 (25.0) 1 (6.3) Nausea 84 (30.7) 1 (0.4) 73(28.7) 1 (0.4) 8 (50.0) 0 (0.0) 2026 Platelet count decreased 79 (28.8) 14 (5.1) 73 (28.7) 11 (4.3) 6 (37.5) 3 (18.8) HAWAII Hyperglycemia 79 (28.8) 4 (1.5) 71 (28.0) 4(1.6) 8 (50.0) 0 (0.0) Alopecia 73 (26.6) 0 (0.0) 66 (26.0) 0 (0.0) 5 (31.3) 0 (0.0) Hypertriglyceridemia 69 (25.2) 6 (2.2) 64 (25.2) 6 (2.4) 5 (31.3) 0 (0.0) Vomiting 64 (23.4) 3 (1.1) 59 (23.2) 3 (1.2) 5 (31.3) 0 (0.0) Constipation 63 (23.0) 0 (0.0) 61 (24.0) 0 (0.0) 2 (12.5) 0 (0.0) Weight decreased 61 (22.3) 2 (0.7) 55 (21.7) 0 (0.0) 6 (37.5) 2 (12.5) Pruritus 56 (20.4) 2 (0.7) 54 (21.3) 2 (0.8) 2 (12.5) 0 (0.0) ALT, alanine transaminase; AST, aspartate aminotransferase; WBC, white blood cell. "includes: hypoesthesia, peripheral sensory neuropathy, peripheral neuropathy J. Zhang et. al, Annals of Oncology, August 2025 --- [Slide 2] Bulumtatug Fuvedotin Phase 1/1b in Solid Tumors: TNBC Cohort Duration of Response Best Overall Response D + All D 100 1.00 no 60 0.75 40 "SUMMIT ON BREAST Remaining (%) in response 0.50 Change from baseline (%) 20 CANCER BOR CA 2026 0 PR HAWAII SD -20 PD 0.25 % -00 0.00 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Months -00 -100 J. Zhang et. al, Annals of Oncology, August 2025 --- [Slide 3] - / ********* Bulumtatug Fuvedotin / Linker-Payload IDM Valine-citrulline PABC MMAE Drug antibody ratio=4 / Y Nectin-4 target Circulation in B Antigen A binding and SUMMIT ON DAR = 4 Blood Internalization BREAST CANCER Protease cleavable MMAE 2026 HAWAII Onestogy Linking strategy: . B Site specific conjugation D Apoptosis Tumor Cell C Drug Release --- [Slide 4] High Nectin-4 expression is associated with tumor growth and progression Nectin-4 Nectin-4 is expressed at low Nectin-4 overexpression ********* levels in a small proportion of is associated with tumor Cancer cell normal tissues: progression: High expression of Nectin-4 Tonsils Esophagus 70-74% Trachea, VOTA Esophagus & Nasopharynx Lung 68% Promoting tumor Promoting proliferation angiogenesis Breast 58-64% Liver 68% Modulation of tumor Promoting Stomach 60% immunity lymphangiogenesis Embryonic & Kidney 36-48% Placental tissues 026 Promoting epithelial- Gall AWAII mesenchymal transition 63% Bladder Skin Bladder 60-90% Cervix 67-90% Tumor progression Adapted from: https://doi org/10 1016/) breast 2024 103838 D et al. 2024 Front Oncol 2024 Mar 28 1354543 PMID: 38606099 Wong et of, 2025 Wang, rufei et of The Breast, Volume 79, 103838 Challito- Eid et at, 2016, Poviove et at, 2013; M-Robet et of, 2017; Siddharth et of, 2017; Zeindler et al. 2019,
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AKTX-101: a TROP2 ADC with a payload targeting RNA splicing disruptionSara Hurvitz

AKTX-101 is a differentiated TROP2 ADC with a PH1 payload targeting the SF3B1 spliceosome complex to disrupt RNA splicing. Preclinical models show activity in topo-I-, T-DXd- and trastuzumab-resistant breast cancer; Phase I initiation is projected for mid-2027: Dr. Sara Hurvitz @fredhutch #DAVABreast

2026 Kona Breast Cancer Summit slide — Sara Hurvitz, AKTX-101: a TROP2 ADC with a payload targeting RNA splicing disruption2026 Kona Breast Cancer Summit slide — Sara Hurvitz, AKTX-101: a TROP2 ADC with a payload targeting RNA splicing disruption2026 Kona Breast Cancer Summit slide — Sara Hurvitz, AKTX-101: a TROP2 ADC with a payload targeting RNA splicing disruption2026 Kona Breast Cancer Summit slide — Sara Hurvitz, AKTX-101: a TROP2 ADC with a payload targeting RNA splicing disruption
[Slide 1] AKTX-101 Path to Clinic: Projected Phase 1 Initiation By Mid-2027 Activity 2026 2027 IND / CTA Supportive Prectinical Enabling Activities Studies GLP Toxicology CMC Scale Up (Preclinical) IND/CTA Timeline Pre-IND Filing FIH Start Consultation (IND/CTA) Dose Escalation you SUMMIT ON BREAST XDC CANCER ASCO Strategic Partnership KRAS activity data 2026 for Trop2 ADC HAWAII DAVAOnestegy CONCER AACR whitehawk TRERAPEUTICS Differentiated Trop2 Collaboration on ADC vs current class Dual ADC payloads Fred Hutch Cancer Center 520 Slide content courtesy of Akan --- [Slide 2] AKTX-101 (Trop2 PH1 ADC) is more potent compared to current Trop2 ADCs in resistant breast cancer models AKTX-101 is the blue line in each graph T-DXd resistant Topoisomerase resistant Trastuzumab resistant JIMT-1, SOC Trastuzumab deruxtecan HCC 1954, SOC Trastuzumab deruxtecan KPL-4, SOC Trastuzumab deruxtecan 120 120 120 AKTX-101 AKTX-191 AKTX-101 100 Datopotamab deruidecan 100 Detopotemab 100 Datopotamab deructecan Sacituzume tinamotican trumotecan Sactuzumab trumotecan 50 Sectuzumab govitecan 50 Sactuzumab govitecan Transfurnab deruivecan 60 Trastuzumab tenadecan Sacituzumab govitecan Breast Creptation 60 KILL Ciaplatin Trastuzumab deruxtecan KILL / 60 40 * %KILL 60 Cisplatin 40 * 40 20 20 20 0 0 0 -20 -20 20 9 -8 -7 6 5 T -3 -2 -1 0 1 2 3 -9 8 -7 6 -5 . 3 -2 1 0 1 2 3 0 -8 -7 -6 -5 T 3 -2 -1 0 1 2 3 log[Test article](uM) log[Test article)(pM) log[Test article](pM) SUMMIT ON BREAST CANCER 2026 HAWAII DAVA/Oreslogy TROP2/ Datopotamab deruxtecan (Dato-Dxd) TROP2/ Sacituzumab govitecan (Trodelvy/ Saci/ S.G. } Topoisomerase I TROP2/ Sacituzumab tirumotecan (Sac-TMT) payloads Her2/ Trastuzumab deruxtecan (Enhertu) Fred Hutch Cancer Center 517 --- [Slide 3] PH1 Payload Has Several Competitive Advantages Relative To Current ADC Payloads Attribute PH1 Payload Topo1 Inhibitors Microtubule Inhibitors Optimal Potency as a <5 nanomolar IC50 5-20x nanomolar IC50 < 1 nanomolar IC50 Cytotoxic agent Susceptible to MDR No — payload not subject to this tumor Yes - Creates tumor resistance Yes - Creates tumor resistance Transporters resistance mechanism B cell expansion / IgM antibody Immune Activation cell killing SUMMIT ON Neutrophil expansion Immunogenic Cell Death (ICD) Immunogenic Cell Death (ICD) BREAST CANCER Macrophage activation 2026 Mitigate Off-target Yes No No HAWAII Toxicities (Y/N) Non-cleavable linker Cleavable linker Cleavable linker Non-permeable linker-payload Permeable linker-payload Permeable linker-payload Observed Side Effects Transient/Reversible Transaminitis Significant off-target toxicities Significant off-target toxicities Mild reduction in and therapy discontinuations and therapy discontinuations platelets(Reversible) ILD (DXd), Gut Toxicity, Neuropathies, Ocular and Ulcers Bone Marrow toxicities Slide content courtesy of Akan --- [Slide 4] PH1 Targets the SF3B1 Spliceosome Complex to Disrupt RNA Splicing and Drive Cancer Cell Death 1 PH1 Payload > 2 PH1 Binds SF3B1 > 3 RNA Splicing > 4 Cellular > 5 Cancer Cell Death Enters Cell in the Spliceosome Disruption Consequences & Immune Activation Depletion of Normal Splicing Essential Proteins SF3B1 Pre-mRNA X PHF5A Aberrant Splicing Mis-spliced SUMMIT ON Transcripts BREAST PH1 CANCER AAAAA 2026 Mis-spliced proteins may HAWAII generate neoantigens that stimulate adaptive immune Primary Driver of Cytotoxicity Potential Immune Benefit responses Depletion of essential proteins resulting from splicing Mis-spliced proteins may generate neoantigens that can disruption drives potent and broad cytotoxic activity stimulate adaptive anti-tumor immune responses Fred Hutch Cancer Center 513
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Selective CDK4/CDK2-Targeting Agents

Moderator · Joshua Gruber
PM3 of 5 with slides

Starting Now: Selective CDK4/CDK2-targeting Agents Moderator: Dr. Joshua Gruber Stay tuned for insightful talks on next-generation cell-cycle targeting strategies in breast cancer #DAVABreast

2026 Kona Breast Cancer Summit — Selective CDK4/CDK2-Targeting Agents session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗

Panel on CDK4 and CDK2 inhibitor #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — Selective CDK4/CDK2-Targeting Agents session
[Slide 1] 8 8 8 & & 8 & & D DAVAOncology DAVAOncology DAVAC D ...facilitating successful drug development ...facilitating successful drug development ...facilitating success 8 B & & R KONA BREAST CANCER SUMMIT in B & & DAVA Oncology D 8 8 B 4TH SUMMIT ON BREAST B 8 & CANCER 2026 DAVAOncology HAWAII CANCER MODERATOR & 8 8 & & & DAVAOncology ...facilitating successful drug development focilitating DAVAOncology successful drug development DAVAOnolog Oncology B D nc 201 DAVAOncol MAG DiVAOncology DAVAOncology™ DAVAOncology DAVAOncology DAVAOncology™ DAVAC DAVAOrcology DAVAOrcology® DAVAOncology DAVAOncology DAVAO
VVinay Jain@VinayJaink9vh2026-08-21Source post on X ↗
FourLight-3: atirmociclib vs CDK4/6 inhibition in treatment-naive HR+/HER2- BCAntonio Giordano
FourLight-3
BGB-43395, a CDK4 inhibitor in development for breast cancerKatherine Clifton

Dr. Katherine Clifton from @WashU presents on BGB-43395-101 (NCT06120283): in 1L HR+/HER2−, CDK4/6i-naive breast cancer, BGB-43395 + letrozole achieved confirmed ORR 63.2%, DCR 100%, and 6-mo PFS 94.7% (n=19). PFS/DOR remain immature. #DAVABreast

2026 Kona Breast Cancer Summit slide — Katherine Clifton, BGB-43395, a CDK4 inhibitor in development for breast cancer2026 Kona Breast Cancer Summit slide — Katherine Clifton, BGB-43395, a CDK4 inhibitor in development for breast cancer2026 Kona Breast Cancer Summit slide — Katherine Clifton, BGB-43395, a CDK4 inhibitor in development for breast cancer2026 Kona Breast Cancer Summit slide — Katherine Clifton, BGB-43395, a CDK4 inhibitor in development for breast cancer
[Slide 1] Phase 1a/1b BGB-43395-101 (NCT06120283) first-in- human open-label study 1 Phase to Global Dose Escalation Safety Expansion (SE) Dose Expansion (DE) Key Eligibility Criteria (SE2 and DE2) Part LA monotherapy 581 21- BC Adults with advanced or metastatic HR+/HER2 breast cancer with no untreated or uncontrolled Sold durse - brain metastases nca 40 00 BD No prior systemic therapies in the advanced or metastatic setting ON Use of GnRH agonists required for premenopausal females Part - 43295 investment SE2: DEZ - BREAST 26.1 I BC BC Other inclusion criteria included measurable disease per RECIST v1.1 and ECOG performance CANCER **** - I 120 mg 80 000-43395 introduce BGB-43395 latrazale status st pe-sap ! 2026 HAWAII Part NO: introache done - 120 - GO ng BD Study endpoints Primary Safety Part ID DGS 43395 elecestrant Secondary (512) DOR, zu Exploratory 2 dose levels 1 I I I i $ Goel et al, ASCO 2026 Poster Presentation --- [Slide 2] 60 Best Overall Response with Confirmation 50 Partial Response (Confirmed) 40 Stable Disease 30 Best Percentage 20 10 Change From 0 0 Baseline Best Change from Baseline (%) -10 -20 16 -20 22 -23 -30 -30 -40 36 40 -42 -50 -46 -48 HOWALT ON -60 -55 -55 57 BREAST 60 -70 66 CANCER 69 -80 2026 HAWAII -90 86 100 96 Uncontimed persal response. Abbreviation BD, twice per day Goel et al, ASCO 2026 Poster Presentation --- [Slide 3] Anti-Tumor BGB-43395 BGB-43395 BGB-43395 Activity 240 mg BID 400 mg BID 600 mg BID Outcomes + letrozole + etrozole + letrozole responses by investigator per RECIST 1.1) (n=19) (n=19) (n=20) Best overall response, n (%)* Complete response 1(5.3) 0 0 Unconfirmed partial response 13 (68.4) 14 (73.7)* 11(55.0) Median time-to-response Confirmed partial response 12 (63.2) 12 (63.2) 11(55.0) Stable disease 5(26.3) 7(36.8) 8(40.0) was 3.7 months Progressive disease 1(5.3) 0 0 Data for median duration of Not evaluable 0 0 1(5.0) response and PFS not mature Unconfirmed ORR (95% CI). %[n] 73.7 (48.8-90.9) [14] 73.7 (48.8-90.9) [14] 55.0 (31.5-76.9) [11] HUMMIT Confirmed ORR (95% CI). % [n] 68.4 (43.4-87.4) [13] 63.2 (38.4-83.7) [12] 55.0 (31.5-76.9) [11] BREAST 6-month PFS rate in the 400 Disease control rate (95% CI), % 94.7 (74.0-99.9) 100 (82.4-100) 95 0 (75.1-99.9) CANCER mg BID arm was 94.7% Clinical benefit rate (95% CI). % 94.7 (74.0-99.9) 94.7(74.0-99.9) 75.0 (50.9-91.3) 2026 "As responses confirmed unless noted HAWAII Strong pharmacodynamic By the data cutoff date of April 30, 2026. one patient each in 240 mg and 400 mg cohorts with an unconfirmed partial response remained on treatment effects, indicated by TK1 Best overall response of complete or partial response, or stable disease for >24 weeks reduction and ctDNA Abbreviations BID, twice per day. ORR, overall response rate decrease Goel et at, ASCO 2026 Poster Presentation --- [Slide 4] GI TRAEs With Without feed (n=31) With food (n-8) Grade 2 Gradel Grade 1 100% MY " VS Without non us & Proporter patients 8 in 60% Food " 42% 40% $ 55% ses 5 20% SUMMIT ON 18% $ BREAST CANCER us 0% Diarrhes I Visiting 2026 HAWAII Goel et al, ASCO 2026 Poster Presentation
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-20Source post on X ↗
RGT-419B, a unique CDK4+ inhibitorRebecca Shatsky
Tegtociclib (PF-07104091), a selective CDK2 inhibitorAdriana Kahn

Dr. @AdrianaKahnMD from @YaleMed presents at #DAVABreast on tegtociclib (PF-07104091) + atirmociclib (PF-07220060) in pretreated HR+/HER2− mBC: ORR 27.8% and DCR 55.6% in 18 evaluable pts; median PFS was 8.3 mo in the broader n=26 cohort.

2026 Kona Breast Cancer Summit slide — Adriana Kahn, Tegtociclib (PF-07104091), a selective CDK2 inhibitor2026 Kona Breast Cancer Summit slide — Adriana Kahn, Tegtociclib (PF-07104091), a selective CDK2 inhibitor2026 Kona Breast Cancer Summit slide — Adriana Kahn, Tegtociclib (PF-07104091), a selective CDK2 inhibitor2026 Kona Breast Cancer Summit slide — Adriana Kahn, Tegtociclib (PF-07104091), a selective CDK2 inhibitor
[Slide 4] Kaplan-Meier / survival curve — table and text data only
Phase 1b/2 first-in-class novel combination trial of next Yap et al, generation CDK4-selective inhibitor atirmociclib (PF-07220060) ESMO 2024 and next generation CDK2-selective inhibitor PF-07104091 in HR+ HER2- metastatic breast cancer and advanced solid tumors Atirmociclib / Duration of treatment in all patients with HR+ HER2- mBC (n=26) Non-CR/non-PD 200 75 mg BID Ongoing BOR: PR BOR:SD 300 / 150 mg BID BOR: Non-CR/non-PD BOR: PD BOR: NE Prior chemotherapy 200 / 150 mg BID SUMMIT BREAST CANCER 100 / 225 mg BID HAWAII Clinical benefit response rate, n (%) = 13 (50.0%) 300 75 mg BID Median progression-free survival = 8.3 months Median (range) line of therapy: 3 (1-14) Duration in weeks from first dose to last dose on study . Atirmociclib (PF-07220060). BOR=best overall response
[Slide 1] Tegtociclib (PF-07104091): Phase 1 Results Demographics Safety Table 1: Demographic and baseline characteristics Part 1A. SAS Table 2: TEAEs occurring in >20% patients by grade (all causalities, all All patients cycles). Part 1A, SAS (N=35) (including mBC) mBC only Characteristic (N=35) (n=29) Grade Grade Grade Grade Age, median (range). 62.0(32-80) 60.0 (32-80) AEs by PT, n (%) 1 2 3 24 Total* Race, (%) With any TEAE 3 (8.6) 11 (31.4) 18 (51.4) 2 (5.7) 34 (97.1) White 0 (85.7) (82.8) Nausea 12 (34.3) 10 (28.6) 5 (14.3) 0 27(77.1) Black or African American 0 0 Diarrhea 13(37.1) 1 (2.9) 3(8.6) 0 17 (48.6) Asian (2.9) 1 (3.4) Vomiting 12(34.3) 4(11.4) 1 (2.9) 1 0 17 (48.6) Not reported 4(11.4) 4(13.8) Anemia 6(17.1) 7(20.0) 3 (8.6) 0 16 (45.7) Tumor type, n (%) Fatigue 4(11.4) 5(14.3) 7(20.0) 0 16 (45.7) Breast cancer 29(82.9) 29 (100.0) Epithelial ovarian cancer 0 Decreased appetite 6(17.1) 5(14.3) 1 (2.9) 0 12(34.3) 4(11.4) SUNNET Non-small cell lung cancer 1 (2.9) 0 Neutropenia 1(2.9) 3(8.6) 5(14.3) 1(2.9) 10 (28.6) BREAST Triple-negative breast cancer 1 (2.9) 0 Dizziness 8(22.9) 0 0 0 8(22.9) CANCER Baseline ECOG PS. (%) Hyperuricemia 8(22.9) 0 0 0 8 (22.9) 0 7(20.0) 6(20.7) Hypokalemia 3(8.6) 1 (2.9) 4(11.4) 0 8 (22.9) 2026 HAWAII 1 27(77.1) 22 (75.9) ALT increased 5(14.3) 1 (2.9) 1 (2.9) 0 7(20.0) I Not reported 1(2.9) 1 (3.4) AST increased 5(14.3) 2(5.7) 0 0 7(20.0) Prior anticancer surgery, n (%) 27(77.1) (72.4) Headache 6(17.1) 1 (2.9) 0 0 7(20.0) Prior systemic lines of therapy 4.0(1-12) 4.0(2-12) Leukopenia 0 4(11.4) 3 (8.6) 0 7(20.0) advanced/metastatic setting). median (range). n (%) Thrombocytopenia 6(17.1) 0 1 (2.9) 0 7(20.0) Prior CDK4/61, n (%) 29 (82.9) 29 (100.0) includes grade 5 TEAL not related to PF-07104091 AE-adverse event, T-alanine aminotramslerase AST-aspartate eminotrans erase: T-preferred em, SAS-safery Prior fulvestrant n (%) 25 (71.4) 25 (86.2) analysis set. treatment advers se event Prior chemotherapy, n (%) 26 (74.3) (72.4) LCOG Lastern Cooperative Oncology Group performance SERVICE SAS-safity analysis sec metastic breast PF-07104091 300 mg BID was identified as the MTD and selected as the cancer monotherapy RDE. Yap et al, ASCO 2023 --- [Slide 2] Tegtociclib (PF-07104091): Phase 1 Results Efficacy ......... Across all doses, median PFS for all patients, as well as for patients with Figure 4: Waterfall plot of best percent change from baseline in sum of mBC was 3.5 months (95% C1:1.8, 5.3). diameters for patients with mBC (RECIST v1.1) (n=16) Median duration of response for 3 patients with partial responses was 6.5 months (95% C1:6.5, 6.5). 80 60 Table 3: Best overall response based on investigator assessment (RECIST 40 v1.1). Part1 A, Response-evaluable set All patients (including mBC) mBC only" n (%) (N=32) (n=16) Complete response (CR) 0 0 Best Change from Baseline in Sum of Diameters for Target Lesions 20 IL SD SD SD SD PR PR PR 0 PD PD PO PD PO PD PD SD SD -20 - SUMMIT ON Partial response 3 (9.4) 3 (18.8) BREAST -60 Stable disease Part 1A 75 mg BID (n=1) 8 (25.0) 6 (37.5) Part 1A 150 mg BID (n=1) CANCER -80 Non CR/non PD 9 (28.1) 0 Part 1A 225 mg BID (n-6) Part 1A 300 mg BID (n-6) 2026 Progressive disease (PD) 12 (37.5) 7 (43.8) -100 Part IA 375 mg BID (n=1) Part 1A 500 mg BID (n=1) HAWAII Response-evaluable set comprised at participants with measurable disease at baseline who received dose of study treatment and had baseline disease assessment and 21 post baseline disease assessment All participants received prior CDK4/6 inhibitor Only advanced/metastatic and locoregional disease/rec urrence prior Comprised of evaluable patients with prior CDK4/6 (with measurable disease at baseline) therapies were included Only includes participants with target lesions at baseline and a1 non-missing post baseline CDK4/G-CDK4/6 inhibitor, Cemetastatic breast cancer percent change from baseline assessment up to time of PD or new anticancer therapy Confirmed best overall response is presented BID-twice daily mBC=metastatic breast cancer; PO-progressive disease PR-partial response SD=stable disease YaleNewHavenHealth Yale CANCER CENTER Smilow Cancer Hospital Yap et al, ASCO 2023 --- [Slide 3] Phase 1b/2 first-in-class novel combination trial of next Yap et al, generation CDK4-selective inhibitor atirmociclib (PF-07220060) ESMO 2024 and next generation CDK2-selective inhibitor PF-07104091 in ********* HR+ HER2- metastatic breast cancer and advanced solid tumors NW Patients with HR+ HER2- mBC with measurable disease at baseline (n=18ᵃ) 90 80 Objective response rate, n (%): 5 (27.8%) 70 60 Disease control rate, n (%): 10 (55.6%) 50 40 #^ 30 A Best % change from baseline in sum of diameters for target lesions 20 10 # SD SD SD SD PR PR PR PR PR BREAST 0 CANCER -10 PD PD PD SD PD #* -20 2026 an HAWAII -30 -40 Atirmociclib 200 mg BID PF-07104091 75 mg BID (n=3) : -50 Atirmociclib 300 mg BID PF-07104091 150 mg BID (n=4) -60 Atirmociclib 200 mg BID PF-07104091 150 mg BID (n=1) #*^ -70 Atirmociclib 100 mg BID PF-07104091 225 mg BID (n=4) -80 Atirmociclib 300 mg BID PF-07104091 75 mg BID (n=2) Prior chemotherapy -90 ESR1 mutation -100 PI3K pathway mutation & '4 patients had non-evaluable responses and are not shown *Atirmociclib (PF-07220060). All patients received prior CDK4/6i PI3K pathway genes include PIK3CA AKT1 and PTEN Mutations include alterations in elacestrant alpelisib and capivasertib CDx tests Objective response rate includes CR and PR Disease control rate includes CR. PR, SD. and non-CR/non-PD CR=complete response PR=partial response: PD=progressive disease: SD=stable disease
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
Samuraciclib: CDK7 inhibitorSara Hurvitz

Dr. Sara Hurvitz from @fredhutch presents SUMIT-BC: in TP53wt HR+/HER2− advanced BC after CDK4/6i, mPFS of 7.8 mo (360 mg) and 8.5 mo (240 mg) was observed with samuraciclib + fulvestrant vs 5.6 mo with fulvestrant; CBR was 60–63% vs 40%. #DAVABreast

SUMIT-BC
2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Samuraciclib: CDK7 inhibitor2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Samuraciclib: CDK7 inhibitor2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Samuraciclib: CDK7 inhibitor2026 Kona Breast Cancer Summit slide — Sara Hurvitz, Samuraciclib: CDK7 inhibitor
[Slide 1] Profile of oral CDK7 inhibitor Samuraciclib Samuraciclib more potent & Combination efficacy in effective vs atirmociclib in cells abemaciclib resistant PDX model ********* Samuraciclib CDK7i terms - F POX1525 M.t 1,200 Vehicle 1,000 Fulvestrant - Samush NO . Ful-Gamura ***** - I 1 I P*004 500 PACKS - PAR 001 400 / + 200 - I - 0 6 12 18 24 30 . Days treatment Atirmociclib CDK4i SUMMIT on MOT 07129060 Response BREAST - CANCER Despite resistance to multiple - 2026 therapies Samuraciclib still has HAWAII - I activity in combination with a SERD - Guarducchi et at 2024 Clin Cancer Res - 30(9):1889-1905 - Fred Hutch Cancer Center --- [Slide 2] Evidence of samuraciclib clinical activity Disease control rate (CR + PR + SD at any time during study): 53% (19/36*) 240 mg disease control rate: 60% (6/10) 360 mg disease control rate: 64% (7/11) . Prolonged disease control observed in TNBC expansion cohort CT scan of liver metastasis site in patient with confirmed RECIST PR A 59-year-old woman with PIK3CAm HR+ breast cancer receiving samuraciclib 240 mg 1 Screening 16 weeks OD over 7 months achieved a confirmed RECIST PR (139%) Liver metastases Five lines of prior hormonal therapy: exemestane; letrozole; tamoxifen; anastrozole; BREAST fulvestrant CANCER Four lines of prior chemotherapy: paclitaxel; 2026 HAWAII eribulin; capecitabine; 5-FU/epirubicin/cyclophosphamide congr ess 2021 ESMO "36 of 44 patients were evaluable for response patients who received 21 dose of samuracidib, had measurable disease at baseline and had a post-baseline tumour assessment CR. complete response CT. computed tomography FU, fluorouracil; HR hormone receptor OD, once daily. mtPIK3CA mutated phosphatidylinositol- 4,5 bisphosphate 3-kinase catarytic subunit alpha PR. partial response; RECIST, Response Evaluation Criteria in Solid Tumours: SD. stable disease: TNBC. triple negative breast cancer Fred Hutch Cancer Center Krebs et al., ESMO 2021 #230MO --- [Slide 3] TP53wt population - mutation not-detected per baseline ctDNA Samuraciclib 360mg QD + fulvestrant Samuraciclib 240mg QD + fulvestrant Control: fulvestrant 60 50 60 All responders All responders 40 TP53wt 40 TP53wt 40 20 20 20 0 0 ] 0 -20 -20 -20 40 -40 -40 60 60 60 80 $ -80 100 100 100 50 50 50 % change in tumour size 0 % change in tumour size 0 SUMMIT ON % change in tumour size 0 BREAST -50 -50 -50 CANCER 2026 -100 -100 -100 HAWAII 0 4 8 12 16 0 4 8 12 16 0 4 8 12 16 Months Months Months : ORR 55% ORR 25% ORR 29% CBR 69% CBR 65% CBR 46% median PFS 14.5 months median PFS 9.6 months median PFS 6.8 months Fred Hutch Cancer Center 360 mg: TP53 Unselected ORR 33% (6/18) CBR 60% (12/20) mPFS 7.8 mos 240 mg: TP53 Unselected ORR 21% (3/14) CBR 63% (12/19) mPFS 8.5 mos Pernas et al., SABCS 2025 PS1-08-06 Fulvestrant: TP53 Unselected ORR 14% (2/14) CBR 40% (8/20) mPFS 5.6 mos --- [Slide 4] Phase 3 Design: Samuraciclib (CDK7i) + Fulvestrant ......... ********* Samuraciclib 360mg QD Advanced Breast Cancer + Fulvestrant HR+/HER2 N~165 Prior CDK4/6i TP53wt per baseline ctDNA Any ESR1 or PIK3Ca/AKT Samuraciclib 240mg QD + Fulvestrant os status (wild-type or R PFS (BICR) mutant) N~165 Follow-up 1:1:1 randomization N~495 AST CER Split 5% alpha comparison Control Arm 90% Power 2026 mTORi + Endocrine therapy HAWAII (Fulvestrant/exemestane) N~165 Fred Hutch Cancer Center
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗

HER2+ Breast Cancer (Novel Agents and Vaccines)

Moderator · Rebecca Shatsky
PM3 of 5 with slides

Coming up next: HER2+ Breast Cancer (Novel Agents and Vaccines) Moderator: Dr. Rebecca Shatsky Emerging HER2-targeted therapies, novel agents, and vaccine strategies take the podium #DAVABreast

2026 Kona Breast Cancer Summit — HER2+ Breast Cancer (Novel Agents and Vaccines) session
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗

Novel HER2 targeting agents #DavaOnc #DavaBreast

2026 Kona Breast Cancer Summit — HER2+ Breast Cancer (Novel Agents and Vaccines) session
VVinay Jain@VinayJaink9vh2026-08-21Source post on X ↗
Rationale for adding zongertinib with other targeted therapy in HER2+ MBCTaiwo Adesoye
IAM1363, an oral HER2 TKI that penetrates the blood-brain barrierAlison Conlin

In the IAM1363 phase 1/1b study (N=39), nausea (49%), diarrhea (41%), and vomiting (31%) were the most common TEAEs. No grade 4/5 AEs were reported; grade ≥3 GI events were uncommon. Presentation by Dr. @AliConlinMD from @providence at #DAVABreast

2026 Kona Breast Cancer Summit slide — Alison Conlin, IAM1363, an oral HER2 TKI that penetrates the blood-brain barrier2026 Kona Breast Cancer Summit slide — Alison Conlin, IAM1363, an oral HER2 TKI that penetrates the blood-brain barrier2026 Kona Breast Cancer Summit slide — Alison Conlin, IAM1363, an oral HER2 TKI that penetrates the blood-brain barrier2026 Kona Breast Cancer Summit slide — Alison Conlin, IAM1363, an oral HER2 TKI that penetrates the blood-brain barrier
[Slide 1] IAM 1363: Oral Her2neu TKI Superior selectivity (1000x wrt EGFR), to avoid rash and liver tox Activity >20 oncogenic mutants, expanding indications Brain penetrant, to address brain metastases (~40% in breast and lung cancer) Achieved by discovering the only known Type II HER2 TKI In Vivo Selectivity Active on Exon 20 Biochemical HER2 vs Drug (manufacturer) Brain Penetrant Cell pHER2 vs. pEGFR2 Mutations EGFR' IAM1363 (lambic) Yes Yes 3790 5200 . NVL-330 (Nuvalent)* Yes Yes 96% - AST RG-6596 (Roche/Zion) Yes No 5755 - 2026 Sevabertinib (Bayer) No Yes <100 - Tucatinib (Pfizer) Marginal No" 2160 - Zongertinib (BI) No Yes 62.4 24 A safe and effective HER2 TKI demands >1000-fold selectivity VS EGFR IAM1363 achieve this safety window, while expanding addressable population with intracranial and pan-mutant activity --- [Slide 2] IAMB1363 Phase 1/1b study Efficacy: Best Reduction in Target Lesions by Dose Level RECIST and RANO-BM Evaluable Pts* Intra- and 100 Best Overall Response* Participants Treated 960 mg with HER2 Targetable Alterations' extracranial activity RECIST RANO-BM CR, (%) 0 0 PR, (%) 5/18 (28%) 1/3 (33%) Maximum Percentage Tumor Reduction From Baseline Activity across 50 SD, n (%) 9/18 (50%) 2/3 (67%) PD PD PD, (%) 4/18 (22%) 0 HER2 wild-type and PD PD SD PD PD PD mutated, and SD SD SD PD SD across disease 0 SD SD SD SD SD I PD indications SD SD SD SD SD SD SD PR SUMMIT ON 1560 mg RECIST responses PR PD PR Monotherapy BREAST 50 600 mg BID RANO-BM responses PR CANCER 1200 mg activity in heavily 960 mg Treatment ongoing Prior HER2 Therapies 480 mg A - PR pretreated 2026 240 mg Same participant perfusumab, HAWAII RECIST response on .. T-DM, 120 mg RANO-BM response on right PR participants -100 Part Participant . . Cancer Type: to CRC Pa CRC on BC % NC on GEA BC Ps ta On CRC Sal Pr CRC NSC BC * NC NSC RCC GSA NC NSC NC On NSC Majority of HERZ Status: 3+ Mut Amp A 2+ via 2+ A 2* 2+ 1+ 2+ Amp Mut Mat " & 1+ Mut 3+ 3+ Mut Mut Md Amp 2+ Mut 3+ Amp Amp Prier HERO P.T. P.I. x P.T.X. L.P. responses seen - P.T. T.X P.T : T T.M. 1 ! - X T.X X X T.X. X Therapies: X : XU U X.0 M.U post treatment "Includes participants with measurable disease and at least post baseline van. includes confirmed and unconfirmed responses with T-DXd HER2 targetable alterations defined as IMC 1+ amplified or mutated and bolded ESMO 2025 --- [Slide 3] IAMB1363 Phase 1/1b study Efficacy: Treatment Duration by Dose Level C ......... Participant required to discontinue IAM1363 after DLT in C1 CNS and systemic disease stability >6 mos with no intervening anti-cancer therapy BREAST CANCER - 2026 HAWAII Participant with LMD CNS and systemic disease stability ongoing at >7 mos ESMO 2025 --- [Slide 4] IAMB1363 Phase 1/1b study Safety: TEAEs in ≥10% Participants Across Dose Levels AM1363 Dose Level 120mg 00 240mg QD 8. 420mg QD 8 QD QD BD QD Total (N=1) (N=1) (Not) (N=17) (N=3) (N=39) Neusea % Any Grade 0 ((100%) 2(50%) 6(35%) 6(60%) 2(67%) 2(67%) 19(49%) . Grade 3" 0 0 0 0 0 0 0 0 Diserhea, (14) Any Grade 0 0 0 6 (35%) 5(50%) 31100%) 2(67%) (6(41%) . Grade 3* 0 0 0 0 0 0 2(67%) 2(5%) Vomiting (%) Any Orade 0 0 1(25%) 5(29%) 1(10%) 3(100%) 2(67%) 12(31%) . Grade " 0 0 0 0 0 0 0 0 I 2 c Any Grade 0 0 1(25%) 4(24%) 1(10%) 0 1.(33%) 7(18%) 1 ON . Grade 3* 0 0 0 0 0 0 0 0 BREAST 2 I CANCER Any Grade 0 1(100%) 0 2(12%) 1(10%) 0 1.(33%) 5(13%) . Grade 31 0 (100%) 0 0 0 0 0 1(2%) Anemia, (%) 2026 HAWAII Any Grade 0 0 0 2(12%) 2(20%) 0 0 4(10%) - Grade " 0 0 0 0 2(20%) 0 0 2(5%) Decreased appetite, " (%) Any Grade 0 0 1(25%) 1(6%) 1(10%) 0 1(33%) 4(10%) . Grade 3* 0 0 0 0 0 0 0 0 Dehydration (%) Any Grade 0 1(100%) 0 1.(6%) 1(10%) 0 (33%) 4(10%) - Grade " 0 0 0 0 1(10%) 0 0 1(3%) All AES Grade 3 only (PR) Grade . AEs) Both events of Grade 3 derives - the 1560 mg 3000 level resolved after dose hold and initation of and diarribed medication Neither event - Grade 3 - - diseased - related to AM1363 any - investigator ESMO 2025
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
DL-1103a, an anti-SIRPa mAb with trastuzumab deruxtecanChristos Vaklavas

Dr. Christos Vaklavas from @huntsmancancer presents DS-1103a, an anti-SIRPα mAb, + trastuzumab deruxtecan as a strategy to enhance macrophage-mediated ADCP and potentially overcome resistance to HER2-targeted therapy #DAVABreast

2026 Kona Breast Cancer Summit slide — Christos Vaklavas, DL-1103a, an anti-SIRPa mAb with trastuzumab deruxtecan2026 Kona Breast Cancer Summit slide — Christos Vaklavas, DL-1103a, an anti-SIRPa mAb with trastuzumab deruxtecan2026 Kona Breast Cancer Summit slide — Christos Vaklavas, DL-1103a, an anti-SIRPa mAb with trastuzumab deruxtecan2026 Kona Breast Cancer Summit slide — Christos Vaklavas, DL-1103a, an anti-SIRPa mAb with trastuzumab deruxtecan
[Slide 4] Kaplan-Meier / survival curve — table and text data only
A Study of DS-1103a Combination Therapy in Participants With Advanced Solid Tumors (NCT05765851) The Challenge A Progression-free Survival in Hormone Receptor-Positive Cohort Median wPFS and 95% CI. months Median Progression free HER2. Patients Survival (95% CI) HR.HERO- HR-HER2- Probability of Progression free Trastuzumab Deruxtecan Survival Hazard ratio for progression or death, Trastuzumab deruitecan Survive Probability(1) Log-Rank P-Value <0.001 Physician's Choice Physician's choice Months No. Risk Time (months) Trastuzumab denuatecan 331 324 290 265 262 248 218 198 182 165 142 128 107 89 78 73 64 48 37 31 28 17 14 12 7 4 4 1 1 HERO. Physician's choice B Progression-free Survival among All Patients SUMMIT OR BREAST Median Progression-free Median os and 95% CL months Patients Survival (95% CI) HER2. CANCER HR-HER2 Probability of Progression free HR-HER2 Survival Trastuzumab Deruxtecan Physician's Choice HAWAII Log-Rank P-Value 0.001 Hazard ratio for progression or death Trastuzumab denatecan Physician's choice Months No. Risk Trastuzumab derutecan 373 365 325 295 290 272 238 217 201 183 156 142 118 100 13 $1 71 53 42 35 32 21 18 15 I 4 4 1 1 0 Time (months) Physician's choice 184 166 119 93 90 73 60 51 45 34 32 29 26 22 15 13 9 5 4 3 1 1 1 1 1 1 0 HERE- https://clinicaltrials.gov/study/NCT05765551 Modi S. et Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. NEJM 2022 Jul 7;387(1):9-20. dol: 0.1056/NEJMoa2203690 Tarantino P. et al. Outcomes of subsequent treatment regimens after trastuzumab deruxtecan in patients with metastatic breast cancer. JNCI 2025 Nov 1;117(11):2327-2335 doc 10.1093/jnci/djat20.
[Slide 1] Leveraging Innate Immunity Augmenting ADCP in Her2+ persistent breast cancer IgG1 mAb IgG4 IgG4 Weak opsonization Strong opsonization Macrophage FcR Macrophage FcR Macrophage FcR Magrolimab Magrolimab . Cancer Cell Cancer Cell Cancer Cell Her2 CD47 . SIRPa CD47 CD47 DON'T EAT ME! SIRPa SIRPa EAT ME! EAT ME! MDSC Created in HER2 CD47 https://BioRender.com cell BC cell a A B ER*PR*HER2* in vivo innate clearance assay BREAST 30 PI3K NK cell CANCER Tcell / 2 AKT BT474 Res 3 2026 HAWAII BT474 BT474 Res 2 Macrophage - Res 1 BT474 Res 2 Recovered * cella 87474 20 BT474 Res 1 BT474 Parental NF-xB relocation 2 L BT474 BT474 HER2 Parent Fles C047 10 S SRA Y Y + - 0 igG1+igG4 Hu5F9-G4 Trastuzumab Combination HER2 CD47 Macrophage Resistant BC cell expression expression Upton R. of at. Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance PNAS 2021 Jul 20:118(29) e2026849118 doi: 10.1073/pnas.2026849118. Candas-Green D. of al. Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells Nat Commun 2020 Sep 14:11(1):4591 doi: 10 1038/s41467-020-18245-7 --- [Slide 2] Leveraging Innate Immunity Evorpacept (ALX-148), a CD47 blocking fusion protein lgG1 mAb Inactive Fc Inactive Fc No opsonization Strong opsonization Macrophage FcR Macrophage FcR Macrophage FcR Evorpacept Evorpacept Cancer Cell Cancer Cell Cancer Cell Her2 CD47 SIRPa CD47 CD47 DON'T EAT ME! SIRPa SIRPa EAT ME! EAT ME! THE PROBLEM BREAST Coating of aging RBCs No Phagocytosis Need for strong Aging RBCs express CD47 CANCER by evorpacept, no opsonization prophagocytic signal IgG1 mAb Macrophage FoR Inactive Fc 2026 HAWAII CD47 Macrophage FcR CD47 SIRPs Evorpacept Her2 Cancer Cell CD47 SIRPa Created in 04 EAT ME! https://BioRender.com --- [Slide 3] Leveraging Innate Immunity DS-1103a, a SIRPa targeting IgG4 mAb IgG1 mAb No opsonization Strong opsonization Macrophage FcR Macrophage FcR Macrophage FcR Cancer Cell Cancer Cell Cancer Cell Her2 CD47 SIRPa CD47 D47 SIRPa DS-1103a SIRPa DS-1103a DON'T EAT ME! EAT ME! EAT ME! THE (POTENTIAL) PROBLEM Immune attack to SIRPa- Need for strong BREAST No hemophagocytosis expressing myeloid cells prophagocytic signal CANCER IgG1 ADC Macrophage FoR (has not been the case) IgG4 for weak 2026 opsonization HAWAII FcR Macrophage Macrophage FcR SIRPs Her2 Cancer Cell SIRPa CD47 DS-1103a SIRPa 105 EAT ME! Created in
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
Abscopal effects of intratumoral DC vaccines in HER2+ patientsBrian Czerniecki

Dr. @BCzernieckiMD from @MoffittNews presents intratumoral HER2-pulsed cDC1 immunotherapy: local treatment was associated with abscopal responses in regional nodes and distant metastases, supporting systemic immune activation #DAVABreast

2026 Kona Breast Cancer Summit slide — Brian Czerniecki, Abscopal effects of intratumoral DC vaccines in HER2+ patients2026 Kona Breast Cancer Summit slide — Brian Czerniecki, Abscopal effects of intratumoral DC vaccines in HER2+ patients2026 Kona Breast Cancer Summit slide — Brian Czerniecki, Abscopal effects of intratumoral DC vaccines in HER2+ patients2026 Kona Breast Cancer Summit slide — Brian Czerniecki, Abscopal effects of intratumoral DC vaccines in HER2+ patients
[Slide 1] Intratumor Delivery of HER2 pulsed cDC1 combined with anti-HER2 antibody leads to abscopal effect A Treated primary tumors p=0.0105 B Untreated distant tumors C p=0.0095 p=0.0154 100 350 p=0.037 350 p=0.0154 p=0.0002 300 p=0.0326 p=0.0002 300 p=0.0047 Tumor growth (mm2) 250 100 Tumor growth (mm2) 250 200 150 Percent of Survival 50 200 150 100 50 0 50 0 5 10 15 20 25 30 35 40 45 50 55 0 0 0 5 10 15 20 25 30 35 40 45 50 Days 0 5 10 15 20 25 30 35 40 45 50 Control HER2-DC1 7.16.4+7.9.5 Day of study Day of study Control HER2-DC1 7.16.4+7.9.5 HER2-DC1 it.+7.16.4+7.9.5 Control HER2-DC1 * 7.16.4+7.9.5 HER2-DC1i.t.+ 7.16.4+7.9.5 HER2-DC1i.t.+ 7.16.4+7.9.5 BREAST E Percent Survival of TUBO-LMD Mice CANCER p<0.05 3000 ns 100 2500 Naive LMD (v = 10) 2026 p<0.05 p<0.05 HAWAII 4.5-10" Tumor volume (mm3) BC cured with LMD (a = 12) ... 2000 rechallenge Control 1500 CD49b+ NK cells # 10-10 in the tumorimg 1000 Survival * 50 Median HER2-DC1 Name - NO 173 1.5.10 + No.reached 7.16.4+7.9.5 7.8.10 500 H HER2-DC1 Frate -00001 12-10" 7.16.4+7.9.5 0 0 HER2-DC1 s.c.* 0 5 10 15 20 25 30 35 40 45 24-10" 0 7 14 21 28 35 42 40 56 63 7.16.4+7.9.5 Days 0 Days Control . HER2-DC111 + 7.16.4+7.9.5 HER2-OC1LL*7.16.4*7.9.5 --- [Slide 2] Mechanism of Immune Activity in HER2 MCC20915 Phase II pCR Rates 10 100 pCR so RCB 60 % 40 20 Baseline Post cDC1 0 Overall All ER ER All ER+ ER+ All All FR HER2 3+HER2 2+ ER- HER2 3+HER2 2+ HER2 3+HER2 2+ ER Negative ER Positive HER2 3+ vs. 2+ ON BREAST CANCER Turnor biopsies containing Tumor biopsies containing 21 TLS-like immune aggregate 21 TLS-like immune aggregate 60 2026 P5001 P<001 PV 02 80 HAWAII P<0001 4 1527 (14) 60 25/40 743 60 CHCL13 LAMPS 8 40 40 20- trac 427 111 20 543 0 CODE - - - - - I on B. Overall 0 pCR Non-pCR --- [Slide 3] Rationale of addition of a-GalCer a glycolipid to DC therapy (the sponge) Control Pregnancy - charges Unpulsed DC1 (CD1d") Unpulsed DC1 gGalCer DC1 . .. oGalCer DC1 (CD1d") NATOR 300 APC Lipid iNKT cell NK T Tumor Area (mm2) Pre-pregnancy Mammary Gland Document 200 : I Cytokine puno Commany 100d bursts Oncogence - - - DC 100 CD1d allows the immune system to "see" lipids, activating Turnorigenes/s infibition iNKT cells that rapidly steer immune responses. 0 0 10 20 30 40 50 FMO Days SUMMIT ON 20 Control BREAST Unpulsed DC1 CANCER 15 gGalCer DC1 2026 HAWAII % of Live cells Unpulsed DC1 (CD1d) HER-2 iDC MFI=2527 10 gGalCer DC1 (CD1d) 5 HER-2 DC1 MFI=9428 0 90 9A 9A NKT NKT yo T cells CD1d --- [Slide 4] 45 yr old female HER2+ treated with cDC1 pulsed with HER2 and alpha galactosyl ceramide + anti- HER2 antibodies Pre surgery PET/CT scan Post immunotherapy PET/CT scan / P BREAST CANCER 2026 HAWAII
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
Disitamab vedotin, an anti-HER2 ADC for HER2+ metastatic breast cancerMark Pegram

Lobular Breast Cancer

Moderator · Henry Kuerer
PM1 of 3 with slides

Coming up next: Lobular Breast Cancer Moderator: Dr. Henry Kuerer

2026 Kona Breast Cancer Summit — Lobular Breast Cancer session
[Slide 1] Lobular Breast Cancer DAVAOncology Thursday, August 20 2026 I 2:55 PM Arya Roy Corey Speers Moderator: Henry Kuerer Tanmayi Pai
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
RWE data on adjuvant chemotherapy in invasive lobular breast cancerArya Roy
Reducing radiation intensity in select lobular breast cancer patientsCorey Speers

Dr. @cwspeers from @uabmedicine presents data challenging the idea that ILC is intrinsically radioresistant: after lumpectomy + whole-breast RT, long-term local control is comparable to IDC when adequately excised and treated #DAVABreast

2026 Kona Breast Cancer Summit slide — Corey Speers, Reducing radiation intensity in select lobular breast cancer patients2026 Kona Breast Cancer Summit slide — Corey Speers, Reducing radiation intensity in select lobular breast cancer patients2026 Kona Breast Cancer Summit slide — Corey Speers, Reducing radiation intensity in select lobular breast cancer patients2026 Kona Breast Cancer Summit slide — Corey Speers, Reducing radiation intensity in select lobular breast cancer patients
[Slide 1] BREAST CONSERVATION After lumpectomy + whole-breast RT, local control is comparable Ten-year local / locoregional recurrence (%) Braunstein 2015 4.4% Interpretation p=0.08 n=998; modern BCT cohort 5.5% Representative long- term WBI series show no statistically 7% Vo 2006 significant excess of p=0.70 recurrence for ILC. long-term institutional cohort 9% ILC has more positive BREAST 18% margins and re-excisions- CANCER Santiago 2005 p=0.24 but not worse control once older treatment era 12% appropriately treated. 2026 HAWAII 0 5 10 15 20 Histology is not a reason to prefer mastectomy over BCT. ILC IDC Braunstein et al., Breast Cancer Res Treat 2015; Vo et al., Breast J 2006; Santiago et al., Am J Surg 2005. 155 --- [Slide 2] MASTECTOMY Radiation clearly improves outcomes in ILC Population-based ILC mastectomy cohort SEER: patients with a EMERGING 5-year local recurrence definite PMRT indication 5-year breast cancer-specific survival 2025 NCDB 8.7% 84.7 Adjusted HR 0.30 Adjusted 5-year ILC mortality HR with =76% relative 80.9 PMRT reduction ILC IDC 383 ILC patients; median 77 0.66 0.74 ON 2.1% follow-up 7.2 years IDC BREAST 71.4 Interaction p=0.01 CANCER 2026 HAWAII I No PMRT PMRT Diepenmaat of al. 65 70 75 80 85 90 No RT PMRT Dispenmant of al. Radiother Oncol 2009; Stecklein et al. Clin Breast Cancer 2016 Chan of al. SABCS 2025 abstract 156 --- [Slide 3] Bridging ER signaling, DNA damage repair, and radiosensitization with implications for ILC a MCF-7 Tamoxifen b MCF-7 Fulvestrant In ER-positive breast cancer models, "p<001 0.6-g *p*0.05 0.8- : " "p<001 pharmacologic ER inhibition increases radiosensitivity Survival Fraction Surviving Fraction 12 Gy) 0.6- 0.1 0.4- and residual DNA damage. T Survival Fraction 0.1 0.01 0.2- 0.01 DMSO DMSO Survive Fraction 6) a Advestrant 1.33 ± 0.03) 0.2- tamoxifen fulvestrant 1 Radiosensitivity t Residual DNA damage 3 - \ 0.001 0.0 0.001 0 2 4 0 2 4 Dose (Gy) Dose (Gy) DMBO 0 NINE C T47D Tamoxifen d T47D Fulvestrant *p*0.00 *p<0.05 0.8- *p<001 "p<0.001 1.0mg *** Surviving Fraction (2 Gy) 0.6- 0.8- BREAST Lower survival More yH2AX foci 0.1 0.1 CANCER after radiation post-irradiation Sunviel Fraction T 0.4- Michmerhuizen A et al. NPJ Breast Cancer. 2022 0.01 Survival Fraction 2026 Mar 10;8(1):31. DMSO HAWAII Advestrant (MER 10) Surviving Fraction 6 a 0.6- 0.4- 0.01 DMSO 0.2- Michmerhuizen A et al. Br J Cancer. 2022 0.2- termoxiten Advestrant Sep;127(5):927-936. tamoxifen Advestrant 0.001 0.0- 0.001 0.0- 0 2 4 0 2 4 6 Dose (Gy) Dose (Gy) DMSO.5 M SIM Treatment (hours) 72 -24 6 1 RT +6 24 I Tamoxities Fore tace) Figure to.d.f) E2 depletion CSS Figure Tg) UAB MEDICINE Estradol atimulation (Figure th) --- [Slide 4] ILC-REDUCE: a biomarker-enriched lower-dose RT trial Hypothesis: biologically selected ILC can achieve isoeffective locoregional control with a lower RT biologic dose-reducing breast/chest-wall, cardiac, pulmonary, and lymphatic morbidity. WHO ENTERS? STANDARD RT ENDPOINTS 1 Central review: classic Current dose + ISOEFFECTIVE? 5-y IBTR LRR noninferiority RANDOMIZE target volumes 10-y confirmation for late ILC ILC recurrence 2 ER+/HER2-; endocrine illustrative comparator 1:1 26 Gy/5 breast-only I 40 Gy/15 with RNI therapy planned CARDIAC Mean heart/LAD dose; cardiac function biomarkers; late cardiac events 3 Complete resection; Stratify by Dose reduction-not field omission negative margins cohort laterality BREAST stage and age PULMONARY LOWER-DOSE RT Mean lung dose / V20; PFTs; grade >2 CANCER pneumonitis 4 Validated RT-sensitivity / 2026 DDR phenotype Same targets + LYMPHATIC / HAWAII same technique FUNCTION Arm volume / bioimpedance; lymphedema; shoulder function PARALLEL COHORTS -25% lower biologic dose Breast-only RNI cohort selected in a phase I/II run-in Correlatives: ER-MDC1 / HR-NHEJ markers, ctDNA, fibrosis, pain, NO N1 cosmesis and PRO-CTCAE/QoL UAB MEDICINE
DAVA OncologyDAVA Oncology@DAVAOnc2026-08-21Source post on X ↗
FES-PET MRI uses and experience in ER+ and lobular breast cancerTanmayi Pai
8 sessions · 47 talks

Fri, Aug 21, 2026

DNA Damage Repair Deficiencies

Moderator · Joyce O'Shaughnessy
AM5 talks
Beyond PARP inhibition: Investigating alternate DNA repair synthetic lethal targets (ATR, PARG, PLK, and WEE1)Pamela Munster
Lessons learnt from the 8,500 WGS from TCGAGad Getz
DNA Damage Repair defects may result in novel targetable mutationsShridar Ganesan
Adherence to screening guideline in a cohort of 350 women with BRCA1/2 mutationsErin Cobain
Pathways to tumorigenesis in inherited breast cancerTuya Pal

ctDNA and Testing

Moderator · Massimo Cristofanilli
AM6 talks
Evaluating molecular data from liquid biopsies on methylation patterns in breast cancer DNAMassimo Cristofanilli
Tissue-free MRD detection using epigenetic markersTanmayi Pai
Incorporation of Foresight Diagnostics phaseSEQ assay into the Signatera testMinetta Liu
NSABP B-64, ctDNA from NSABP B-64 patients using Exact Biosciences assayMarija Balic
NSABP B-64
Dynamic assessment of endocrine sensitivity in the neoadjuvant settingKarthik Giridhar
ctDNA in adapting therapy in HER2+ve breast cancerAmina Chaudhry

Emerging Drugs Targeting PI3 Kinase/AKT

Moderator · Adam Brufsky
AM3 talks
Tersolisib (STX-478), brain-penetrant allosteric PI3Kα H1047R inhibitorHolly Knoderer
Zovegalisib (RLY-2608), a mutation specific PI3Kα inhibitorChristos Vaklavas
Potential synergy of mutant-selective PI3K and HER2 inhibition in ER+, non-HER2-amplified BCAriella Hanker

Lessons Learnt from Neoadjuvant Trials

Moderator · Laura Esserman
AM6 talks
How do we avoid overtreating small (<3 cm), node-negative TNBC tumors?Joshua Gruber
Oncotype DX maintains its predictive value regardless of HER2 in early-stage breast cancerHadar Goldvaser
Mitigating axillary lymph node resection among patients with robust responses to neoadjuvant therapyHenry Kuerer
Potential to avoid axillary surgery based on ctDNA responseRita Mukhtar
Examining the surgical options in the I-SPY2 trial among young women with breast cancerJordan Jackson
I-SPY2
I-SPY findings on the impact of age on breast cancer outcomes in breast cancer and immune signature statusKelsey Natsuhara
I-SPY

Novel Techniques for Early Detection of Cancer

Moderator · Pamela Munster
AM6 talks
Emerging genetic tools for detecting cancer in "healthy people"Karthik Giridhar
Risk based annual breast cancer screening: WISDOM trialLaura Esserman
WISDOM
Risk on a continuum: Implications of high-risk mutations with incomplete penetranceTuya Pal
Development of the tissue-free, methylation-based assays for indications beyond MRD testingMinetta Liu
Rationale and benefits from a registry for TNBC and high-risk noncancer patientsPriyanka Sharma
Syantra DX, a minimally invasive test for early detection of breast cancer in women with dense breastsEdith Perez

Novel Agents in TNBC

Moderator · Alison Conlin
AM7 talks
ADCs targeting B7H3 or HER2 using N-myristoyltransferase inhibitor as payloadSara Hurvitz
HRD beyond BRCA: Where do PARP inhibitors fit with other DNA repair defects?Pamela Munster
Invikafusp alfa, a bispecific dual T-cell agonist in combination with sacituzumab in neoadjuvant trialsLaura Esserman
Emerging findings for the immunogenic impacts of injected nitric oxide in localized breast tumorsFred Dirbas
Targeting Unfolded protein repair pathways in breast cancerAndrew Brenner
Evaluation of methylation patterns in metastatic breast cancer to identify treatment targetsMarija Balic
Use of roflumilast to prevent pulmonary metastasis in those with high-risk, early-stage TNBCAnna Schreiber

Cellular and Other Immune Approaches

Moderator · Fred Dirbas
PM8 talks
Ivonescimab: a PD-1 x VEGF bispecific in TNBCYuan Yuan
The role of C3 complement signaling in increased-risk breast cancerVictoria Seewaldt
Early clinical experience for an agent targeting P2RY8Dennis Slamon
Background and initial clinical experience for a homegrown CAR T targeting B7H3 in breast cancerYara Abdou
mRNA loaded DC targeting Neo-epitopesKaren Anderson
Findings from single-cell RNA sequencing of bone marrow aspirations and the abscopal effects of cancer vaccinesBrian Czerniecki
Using cytokine analysis of tumor and microenvironment samples to predict responders to immune checkpoint inhibitionPooja Advani
Translational data for using naloxegol to target opioid receptors as a therapeutic approach to prevent cancer progressionKalpna Gupta

Translational Strategies in TNBC

Moderator · Pooja Advani
PM6 talks
Integrating functional organoid profiling with biomarkers in TNBCJennifer Rosenbluth
CyTOF analysis of tumor microenvironment from early stage TNBC post neoadjuvant therapyYuan Yuan
Biomarker-selected and molecularly stratified deescalation and intensification of radiation therapyCorey Speers
Linking MRI-defined background parenchymal enhancement to functional endocrine responsivenessJennifer Rosenbluth
Outcomes for patients with HER2 detected by proteomic analysis that are HER2- by FISH and IHCEmanuel Petricoin
Early detection of breast cancer using a deep proteomics platformPooja Advani
4 sessions · 25 talks

Sat, Aug 22, 2026

CNS Metastases and Public

Moderator · Ajay Dhakal
AM3 talks
Elacestrant + abemaciclib in patients with brain metastasesTomer Wasserman
A machine-learning model to predict patients with a higher risk of brain metastasesAnton Safonov
Rhenium-186 theranostics for carcinomatous meningitisAndrew Brenner

Translational Research in Breast Cancer

Moderator · Leif Ellisen
AM7 talks
Using novel sequencing technologies to assess tumor evolutionGad Getz
Crosstalk between clonal hematopoiesis and breast cancer outcomesShridar Ganesan
Targeting DNA methyltransferases in metastatic TNBC in patients who express high levels of DNMT3ARoberto Leon-Ferre
Metabolic pathways in early-stage HR+ breast cancerCoral Omene
Using the molecular characterization (radiosensitivity index) to detect microenvironmental factors with an impact on sensitivity to irradiationShane Stecklein
Radiation before or after surgery: Investigating benefits and outcomesIrene Wapnir
Employing AI tools to enhance real-time matching of patients to trialsJames Dickerson

Novel ADCs and Inflammatory Breast Cancer: Session II

Moderator · Mark Pegram
AM7 talks
Emerging data on CLDN6-23-ADC, an anti-Claudin-6 antibody-drug conjugate for CLDN6+ BCDennis Slamon
Evidence for micvotabart pelidotin (PYX-201), an ADC targeting extradomain-B fibronectin in the tumor extracellular matrixKatherine Clifton
An anti-FGFR2b ADC in development for ovarian and breast cancer (ALK201)Shou-Ching Tang
Early data for a phospholipid-drug conjugate with I-125 targeting cholesterol rafts enriched in tumor cellsPooja Advani
Outcomes of neoadjuvant therapy in inflammatory breast cancerToshi Iwase
Histologic variability of metaplastic triple-negative breast cancerAshley Matusz-Fisher
Rationale for combining a TROP2-directed antibody-drug conjugate with immune checkpoint inhibition in metaplastic triple-negative breast cancerNeha Verma

Mitigating Toxicities and Improving QOL

Moderator · Lynn Henry
AM8 talks
DPYD for 5-FU and capecitabine: Pharmacogenomics of optimal dosingSandra Swain
Implementing short-term fasting into a chemotherapy regimen to reduce toxicityJenni Sheng
Strategies to mitigate musculoskeletal symptoms using nonpharmacologic approachesLynn Henry
Transdermal curcumin as a potential approach to reduce neuropathy in cancer patientsKalpna Gupta
Using Efinia to deliver electric fields to increase sensitivity to capecitabine in TNBC: Preclinical data and trial rationaleArya Roy
Personalizing dosing and treatment intensity in older adults with breast cancerMina Sedrak
Strategies to improve treatment access in populations in rural and underserved areasAshley Matusz-Fisher
Fully automated abstraction of breast cancer records using off-the-shelf large-language modelsJames Dickerson

Programme, moderators and speaker attributions are transcribed from the official DAVA Oncology agenda. Slides were captured from the meeting's own session feed; every card carries a link back to the post it came from. Aug 18 was arrival and registration — no scientific programme was published for that day.

Enlarged conference slide