Top KOLs Discussing SWITCH
SWITCH Key Slides & Visuals
ESMO 2026 slides
| A: SHR-A1811 (HER2), n=10 | B: SHR-A1921 (TROP2), n=12 | C: SHR-A2009 (HER3), n=12 | D: SHR-A2102 (Nectin-4), n=20 | |
|---|---|---|---|---|
| Partial response, n (%) | 0 (0.0) | 1 (8.3) | 0 (0.0) | 1 (5.0) |
| Stable disease, n (%) | 8 (80.0) | 2 (16.7) | 5 (41.7) | 10 (50.0) |
| Progressive disease, n (%) | 2 (20.0) | 9 (75.0) | 7 (58.3) | 9 (45.0) |
| Confirmed ORR, % (95% CI) | 0.0 (0.0–30.8) | 8.3 (0.2–38.5) | 0.0 (0.0–26.5) | 5.0 (0.1–24.9) |
| DCR, % (95% CI) | 80.0 (44.4–97.5) | 25.0 (5.5–57.2) | 41.7 (15.2–72.3) | 55.0 (31.5–76.9) |
| Bayesian posterior mean ORR (95% CrI) | 4.5% (0.0–21.7) | 11.5% (0.9–32.8) | 3.8% (0.0–18.5) | 7.1% (0.5–21.1) |
| Posterior Pr(ORR ≥20%) (efficacy threshold >0.80) | 0.0324 | 0.1551 | 0.0193 | 0.0319 |
| Cohort | n | Median PFS, months (95% CI) | At risk at 6 months | At risk at 12 months |
|---|---|---|---|---|
| A: SHR-A1811 (HER2) | 10 | 3.0 (1.5–5.7) | 2 | 0 |
| B: SHR-A1921 (TROP2) | 12 | 1.4 (1.0–2.7) | 1 | 1 |
| C: SHR-A2009 (HER3) | 12 | 1.5 (1.3–2.9) | 0 | 0 |
| D: SHR-A2102 (Nectin-4) | 20 | 2.7 (1.3–3.1) | 1 | 0 |
Same slides also posted by @stolaney1, @matteolambe, @PTarantinoMD, @to_be_elizabeth.
| A (HER2) | B (TROP2) | C (HER3) | D (Nectin-4) | |
|---|---|---|---|---|
| Assigned (54 of 58 screened) | 10 | 12 | 12 | 20 |
| Progressive disease | 10 | 12 | 11 | 20 |
| Other discontinuation | 0 | 0 | 1 (vomiting) | 0 |
| Treatment ongoing | 0 | 0 | 0 | 0 |
Same slides also posted by @Dr_ElvinaA.
| First-ADC (ADC1) PFS | n | Second-ADC (ADC2) PFS >3 months |
|---|---|---|
| <5 months | 17 | 35.3% |
| ≥5 months | 37 | 21.6% |
| Comparison | Fisher’s exact P = 0.33 (numerical difference, not significant) |
Same slides also posted by @hoperugo.
| Gene | Mutant / wild-type, n | HR (95% CI) | P |
|---|---|---|---|
| ATM | 9/43 | 0.41 (0.18–0.93) | 0.032 |
| CACNA1C | 6/46 | 3.76 (1.47–9.56) | 0.006 |
| ALK | 7/45 | 2.71 (1.17–6.26) | 0.020 |
Same slides also posted by @DrSGraff, @ElisaAgostinett.
Discussion: Sherene Loi, MD
| Cohort | Target (all TOP1i) | n | cORR | DCR |
|---|---|---|---|---|
| A SHR-A1811 | HER2 | 10 | 0% | 80% |
| B SHR-A1921 | TROP2 | 12 | 8.3% | 25% |
| C SHR-A2009 | HER3 | 12 | 0% | 42% |
| D SHR-A2102 | Nectin-4 | 20 | 5.0% | 55% |
Same slides also posted by @MamMa_mimumemo, @drsarahsam.
KOL-Made Infographics
Summary graphics designed by physicians (not conference slides). Values are as the authors drew them. Click to enlarge.
@ChandrakanthMv
@ChandrakanthMv
@ChandrakanthMv
@ChandrakanthMvPhysician reactions to SWITCH
The worst part about the Switch trial proving what we knew to be true about payload resistance is that ADCs are basically all we have as far as control of brain mets and leptomeningeal disease. For our CNS disease patients chemo just doesnt cut it. #ESMO26 #Breastcancer #ADC
Excellent rapid oral session 2 in #advancedbreastcancer today New advances in #ADC, #CNS treatment in #HER2 #BreastCancer #ESMO26 #ESMOAmbassadors https://t.co/WeRQeOiMxY https://t.co/N2wGI77fL4
SWITCH: Changing the ADC target may not overcome payload resistance. #ESMO26 In TOP1i-ADC–refractory HER2-negative MBC, target switching yielded ORR 0–8.3% and mPFS 1.4–3 months. @Larvol @OncoAlert @KolPulseAI https://t.co/oS0epT3NTJ
SWITCH highlights the limited activity of sequential ADCs after progression in metastatic HER2-negative breast cancer: ORR 0–8.3%, median PFS 1.4–3.0 months @OncoAlert #ESMO26 #BreastCancer #bcsm #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/RaLX9nNSkM
Bulumtatug fuvedotin (BFv): Nectin-4–targeted ADC with an MMAE payload. Given the SWITCH trial results with target switching (ORR <10%, PFS <3 mo), payload switching looks promising. It’s not that simple, but our intuition about ADC resistance is gaining stronger support. #ESMO26 https://t.co/FFUZZv4SMe
Context: bulumtatug fuvedotin (4640RO) is a separate study.
#ESMO2026 very nice discussion by @LoiSher on novel ADC trials and switching. Be sure to watch on line! Beautiful comments about biomarkers. @OncoAlert https://t.co/KFk4A3xhyw
At #ESMO26 Rapid oral abstracts session on advanced #breastcancer Great discussion by @LoiSher addressing the question “what works after treatment with a TOP1 ADC?” Changing the target but keeping the payload does not work; switching payload works modestly @OncoAlert https://t.co/fubF0XWerU
🔥‼️ It is high time to STOP switching from one TOP1i-based ADC to another after progression! ⛔️ The SWITCH trial adds to mounting evidence: changing the target is NOT enough 👉 Important: 2 responses, both after MMAE-based ADCs We URGENTLY need non-TOP1i-based ADCs! #ESMO26 https://t.co/qJI3ay8Yys
First prospective switch trial of Top1 ADC post Top1 ADC in MBC. 0-8% ORR Switching target with same payload simply does not work. Resistance is in payload. Let’s stop talking about “sequencing”. It simply does not work. We need new payloads. #MBC #BCSM #ESMO26 https://t.co/YremeiDWkt
#ESMO26 ADCs in MBC: SYS6043 (B7-H3, TOP1i) ORR 46% HR+, 71% TNBC & HER2+. But SWITCH: after ADC progression, new target + same TOP1i payload → ORR 0–8%. Changing the receptor isn’t enough; switch the payload too. Nectin-4/MMAE ADCs may be the answer. #bcsm https://t.co/RFPrWkZF1x
Context: SYS6043 (5RO) is a separate study.
🔬 SWITCH In mi opinion one of the most informative trials at #ESMO26 Small but highly informative prospective phII trial (n=54) evaluating ADC sequencing in HER2− ABC. After progression on TOP1i-based ADCs, switching targets while retaining a TOP1i payload yielded no objective responses. For future trials design 👨💻An important signal of payload cross-resistance: changing the target may NOT be enough! @myESMO
ADC sequentialのSWITCH試験は、重要なネガティブstudyとしてDIscussionで紹介されている。 MMAE（tublin阻害薬）をペイロードにしたADCが、Top1-ADC 後でも効果を示していたことから、ターゲットのスイッチよりもペイロードを変える方が、臨床的には有効なのだろう。 #ESMO26 https://t.co/K5UuGsuFh5
SWITCH試験。 Cohort A:SHR-A1811(trastuzumab rezetecan、HER2) Cohort B:SHR-A1921(TROP2) Cohort C:SHR-A2009(HER3) Cohort D:SHR-A2102(Nectin-4) 奏効割合は0%、8.3%、0%、5%でした。mPFSも3.0, 1.4, 1.5, 2.7カ月と短めでした。 奏効したのは、MMAE系ADC(disitamab vedotin)からtopo-I系ADCへ切り替えた2例だけでした。 日本国内の使用可能なADCはT-DXd、SG、Dato-DXdの3剤がいずれもtopo-I系ペイロードになります。このため、HR+/HER2-lowでT-DXdの後にSGやDato-DXdを使う、TNBCでSGの後にT-DXdを使う、といった実臨床の逐次投与で、2剤目以降の効果は限られる可能性が危惧されます。ただ、奏効割合やPFSを踏まえると、Phase3試験の結果などでもアンスラ・タキサン以外では今回のPhase2データと同程度が示されているということで、オプションとはいえるかなと思っています。 #ESMO26
Switch w/TOP1i-ADCs had limited efficacy in TOP1i-based ADC-refractory HER2-neg MBC 🔹ORR 0-8.3% 🔹Median PFS 1.4-3.0 mos 🧬Preliminary biomarkers work suggest ATM mut as a potential predictor of response #ESMO26 @OncoAlert https://t.co/dF7H5HYOQz
#ESMO2026 Lei Fan presents a small prospective ADC switching trial largely post topo1 ADCs. Low response and PFS in general. Fast PD on 1st line predicted better ORR on next ADC. New payloads urgently needed. @OncoAlert https://t.co/N4Dz5XSEvl
The SWITCH platform study 🇨🇳 suggests that payload cross-resistance is a limitation for ADC sequencing for the treatment of metastatic breast cancer. #ESMO26 #ESMOAmbassadors @myESMO @PTarantinoMD @LoiSher @E_de_Azambuja https://t.co/2MCXabMt9f
At #ESMO26 Rapid oral abstracts on advanced #breastcancer Results of the SWITCH trial, on the efficacy of ADC post ADC in HER2-neg aBC Poor response to ADC after ADC; response only if payload changed Payload resistance seems main determinant of resistance to ADC @OncoAlert https://t.co/GRUYtlXPlY
The SWITCH trial adds important prospective data on TOPO1 ADC sequencing. Among TOPO1-ADC pretreated pts with MBC, barely any activity was observed with a second TOPO1 ADC, with <10% ORR and <3 mo PFS, despite switching target. Payload cross-resistance dominates. #ESMOAmbassadors https://t.co/cDuYuM5qNv
SWITCH Trial (Phase II) #ESMO26 In HER2-negative metastatic breast cancer previously treated with ADCs, switching ADC targets showed limited efficacy. ORR: 0–8.3% Median PFS: 1.4–3.0 months Suggest potential payload cross-resistance and highlight the need for ADCs with novel payloads.
#ESMO26 | SWITCH In this 54-patient phase II trial, switching targets after a TOP1-based ADC produced no responses when the payload class remained unchanged. A small study with an important message: as ADC numbers grow, we need payload diversity as much as target diversity to overcome resistance.
Oral abstract #BreastCancer session at #ESMO26: prospective data on ADC sequencing showing very limited activity with the second ADC by only changing the target @OncoAlert @myESMO https://t.co/y6tSux2vaL
HER2- MBCに対してADCのペイロードは同じでターゲットを変えて効果がどうなるかをみたSWITCH試験。 response rateは0-8.3%。mPFSで1.4-3.0m。 同じペイロードではターゲットを変えても効果はかなり限定的。これまでも似た報告はされてきましたが、厳しい結果。 #ESMO26 https://t.co/TcIahup3Ms
SWITCH trial: ADC switching 25% HR+ 75% TNBC ORR: 0-8.3%, PFS 1.4-3.0 mo @OncoAlert #ESMO26 https://t.co/PWb3X6UIxs
📌 Target switching with conserved-payload novel ADCs in patients with metastatic breast cancer following prior ADC therapy (SWITCH): A prospective, open-label, phase 2 platform trial ✨Lei Fan #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/MenVVFZIFc
ADCの選択肢が増えたらどうしていくか、あらたにわいてくる議論 SWITCH試験を踏まえると、Topo1 ADCシークエンスは、アンスラタキサン以外の、横並び選択肢だろうか。 @AyumiSaito0809 #JSCO26 https://t.co/vIzfNcH4XR https://t.co/oVs0Mb0s5S
Context: posted on October 23 (JSCO 2026), before the ESMO presentation.
#ESMO2026. The ADC question I am watching this week is not which target. It is which payload, and in what order. Monday, one breast session: SWITCH (4RO), ADC after ADC. OptiTROP-Breast01 (4639RO), final OS for sac-TMT in pretreated TNBC. Bulumtatug fuvedotin (4640RO), MMAE after a TopoI ADC. Same day, Presidential Symposium: TroFuse-005 (LBA11), sac-TMT in previously treated endometrial cancer. TROP2 is expressed in most endometrial tumors. If sac-TMT works, the target was never the hard part. The hard part is what comes after. I give the best treatment first. The tumor that progresses is then already resistant to that payload, and the next line needs a different mechanism. That is where we need more small molecule targeted drugs, not another antibody carrying the same payload. #gyncsm #bcsm
Context: posted on October 22, before the presentation.
SWITCH vs SATEEN | ADC Sequencing: Is the Payload the Problem? Different populations. Different strategies. Same ORR: 3.7%. 🔹 SWITCH: HER2-negative MBC — 2/54 responses. No responses after TOP1i → TOP1i switching. 🔹 SATEEN: HER2-positive MBC after T-DXd — SG + trastuzumab. ORR 3.7%; median PFS 2.3 months. Key question: Are we changing the ADC target while retaining the same resistance problem? TAKE-HOME: Target switching alone may be insufficient. Payload-class cross-resistance is plausible, but unproven. Diversifying the cytotoxic mechanism deserves investigation. Different Targets. Same Payload Class. Limited Responses. 📚 References: SWITCH (ESMO 2026); SATEEN (published phase II study). #MVOnco #ESMO2026 #BreastCancer #ADC #Oncology
Context: posted on October 21, before the presentation. SATEEN is a separate study.
SWITCH | ESMO 2026 New Target. Same Payload. Same Resistance? Can switching the ADC target overcome resistance in metastatic breast cancer? 🔹 Phase II | 54 patients | HER2-negative mBC 🔹 94.4% previously exposed to TOP1i-based ADCs 🔹 Only 2/54 responded (3.7%) 🔹 Both responses followed a switch from an MMAE-based ADC to a TOP1i-based ADC. 🔹 No responses after switching between ADCs within the same TOP1i payload class. Key lesson: Different target ≠ Different killing mechanism. Payload cross-resistance may be a major obstacle to ADC sequencing. Change the weapon, not just the address? ⚠️ Small, hypothesis-generating study. Not practice-changing. #MVOnco #ESMO2026 #BreastCancer #ADC #Oncology
Context: posted on October 21, from the 4RO abstract, before the presentation.
We now have prospective data with TOPO1 ADC sequencing from: - SATEEN (#ESMOBreast26) - HER3-DXd (#ESMOBreast26) - SWITCH (upcoming #ESMO26) All validate prior retrospective data, showing that TOPO1 ADC resistance is not overcome by target switch. New payloads urgently needed. https://t.co/tsl3hjj9o5
Context: posted on October 19, before the presentation.
#ESMO26 | SWITCH – Phase II In mBC progressing after ADC therapy, switching the target antigen while continuing with the same TOP1 inhibitor payload class resulted in ORRs of only 0–8.3%. Although the sample size was small and the patient population heterogeneous, changing the target antigen alone does not appear sufficient to overcome resistance.
Context: posted on October 19, from the 4RO abstract, before the presentation.
Payload, not target?
“Switching target with same payload simply does not work”
Several physicians read the result as conclusive for TOP1i-to-TOP1i sequencing. Sarah Sammons, MD, wrote that switching target with the same payload “simply does not work” and that resistance is in the payload; Paolo Tarantino, MD, concluded “Payload cross-resistance dominates”; Giampaolo Bianchini, MD, called for an end to switching from one TOP1i-based ADC to another after progression. Sara Tolaney, MD, posted the response and PFS figures; Hope Rugo, MD, wrote that new payloads are urgently needed. The discussant, Sherene Loi, MD, labeled SWITCH an important negative study and “practice-informing” on her practice-impact slide.
How firm is the evidence?
Loi’s caveats: allocation followed prior treatment rather than true randomization; cohorts were small (10–20 patients) and mixed HR-positive and triple-negative disease; 11% had ECOG performance status 2; the payload-switch signal is two patients; and the ATM/ctDNA finding needs validation with control for clonal hematopoiesis. Earlier, on October 21, MV Chandrakanth, MD, described SWITCH as a small, hypothesis-generating study, and Pablo Jara Martín, MD, called it small but highly informative.
What should follow a TOP1i ADC?
Loi’s take-home messages: every ADC trial should report the prior ADC target, payload and previous PFS; payload-defined sequences should be randomized against active chemotherapy; biopsy or ctDNA should be obtained at ADC progression; and novel payloads and dual-payload ADCs are needed. Tatsunori Shimoi, MD, noted that the ADCs available in Japan (T-DXd, sacituzumab govitecan, Dato-DXd) all carry TOP1i payloads. Rebecca Shatsky, MD, raised the cost of the finding for patients with brain metastases or leptomeningeal disease, for whom ADCs are a main source of CNS control.
Context: a separate study of a different payload (4640RO)
In the same session, Yanchun Meng presented a separate single-arm phase 2 study (4640RO; NCT06492005; sponsor Mabwell) of bulumtatug fuvedotin (9MW2821), a Nectin-4 ADC with an MMAE payload, in locally advanced or metastatic TNBC after TOP1i-based ADCs. Among 60 evaluable patients, all previously treated with a TOP1i ADC, ORR was 30.0% (95% CI 18.85–43.21) and median PFS 3.7 months (2.96–4.34) (4640RO abstract, data cutoff Apr 10, 2026). Loi called this hypothesis-generating and said a randomized comparison against chemotherapy or other standard care is needed. It is not part of SWITCH, and bulumtatug fuvedotin is investigational. ClinicalTrials.gov NCT06492005
SWITCH Trial Design
SWITCH asked whether changing the antibody target of an ADC, while keeping a topoisomerase I inhibitor payload, can overcome resistance after a prior ADC in HER2-negative metastatic breast cancer. Led by Fudan University Shanghai Cancer Center (principal investigator Zhimin Shao, MD), the platform enrolled patients between October 21, 2024 and December 30, 2025 and assigned 54 of 58 screened patients to one of four Jiangsu Hengrui ADCs. The registry lists further cohorts not reported at ESMO 2026, including combinations, other ADCs and physician’s choice, with an estimated enrollment of 160; the study is recruiting.
Study Design
Prospective, open-label phase 2 platform (NCT06649331). Assignment to cohorts was based on prior ADC treatment (described as randomized). Each cohort planned 10–30 patients with an independent Bayesian predictive probability design.
Population
HER2-negative metastatic breast cancer with progression on at least one prior ADC; measurable disease (RECIST v1.1); HR-positive disease required prior endocrine therapy with a CDK4/6 inhibitor. 94.4% had prior TOP1i-ADC exposure.
Interventions
Cohort A SHR-A1811 4.8 mg/kg (HER2); B SHR-A1921 3.0 mg/kg (TROP2); C SHR-A2009 8 mg/kg (HER3); D SHR-A2102 8 mg/kg (Nectin-4); all IV every 3 weeks until progression or intolerance.
Endpoints
Primary: investigator-assessed confirmed ORR. Secondary: DCR, PFS, OS, safety. Exploratory: biomarker analysis (ctDNA).
Presenter & Discussant
Presenter Lei Fan, MD (Fudan University Shanghai Cancer Center); first author Xiyu Liu. Discussant Sherene Loi, MD (Peter MacCallum Cancer Centre).
Data Cuts
Abstract: Mar 14, 2026. Presentation: Jul 31, 2026 (median follow-up 8.6 months, range 4.7–14.0). OS was not reported.
SWITCH Sources
SWITCH Questions
What is the SWITCH trial?
SWITCH (NCT06649331) is a prospective, open-label phase 2 platform trial at Fudan University Shanghai Cancer Center in patients with HER2-negative metastatic breast cancer whose disease progressed on at least one prior antibody-drug conjugate. Patients were assigned, based on their prior treatment, to one of four novel ADCs from Jiangsu Hengrui that target different antigens (HER2, TROP2, HER3 or Nectin-4) but all carry a topoisomerase I inhibitor (TOP1i) payload. Design: Trial Design.
What did SWITCH show at ESMO 2026?
Activity was limited in every cohort. Confirmed ORR, the primary endpoint, was 0% with SHR-A1811 (HER2, n=10), 8.3% with SHR-A1921 (TROP2, n=12), 0% with SHR-A2009 (HER3, n=12) and 5.0% with SHR-A2102 (Nectin-4, n=20); median PFS ranged from 1.4 to 3.0 months (4RO slides, data cutoff July 31, 2026). Figures: At a Glance.
Which patients responded?
Only 2 of 54 patients responded, one in the TROP2 cohort and one in the Nectin-4 cohort. Both had previously received disitamab vedotin (RC48), an ADC with a microtubule-inhibitor (MMAE) payload, so their switch was to a different payload class. No responses occurred after switching between ADCs with the same TOP1i payload class (4RO abstract and slides).
Why does SWITCH matter for ADC sequencing?
94.4% of patients had previously received a TOP1i-based ADC. The investigators concluded that payload cross-resistance may be a major determinant of failure after an ADC and that changing the antibody target alone appears insufficient. The discussant, Sherene Loi, called it an important negative study and listed caveats: allocation by prior treatment rather than true randomization, small cohorts, a mixed HR-positive and triple-negative population, and a payload-switch signal based on two patients.
Are these ADCs approved?
No. SHR-A1811 (trastuzumab rezetecan), SHR-A1921, SHR-A2009 (ruzaltatug rezetecan) and SHR-A2102 are investigational in this setting, and none is FDA approved. SWITCH does not change any label; it informs how future ADC sequencing trials are designed.
Who presented SWITCH?
Lei Fan, MD, of Fudan University Shanghai Cancer Center presented abstract 4RO on October 26, 2026 in the Rapid Oral session on advanced breast cancer, as listed in the ESMO program and on the title slide; the first author on the abstract is Xiyu Liu. Sherene Loi, MD, of the Peter MacCallum Cancer Centre was the invited discussant.