Lung cancer trials by physician discussion
Physician posts on X, October 23–25.
DeLLphi-305 drew far more physician posts than any other lung trial. OptiTROP-Lung06, PERSEE, SARON, OptiTROP-Lung04 and SigVie-002 were all presented on Day 3 (October 25) in the same proffered paper session. KRASCENDO-1 and SAFFRON were presented later on October 25.
Small cell lung cancer
DeLLphi-305: tarlatamab + durvalumab as first-line maintenance in ES-SCLC
Phase 3, N=563: tarlatamab (IMDELLTRA, Amgen) plus durvalumab vs durvalumab alone after first-line chemo-immunotherapy. Median OS 21.1 vs 12.7 months, HR 0.42 (95% CI 0.32–0.54), P<0.001, at a prespecified interim analysis. 12-month OS 79.4% vs 53.3%. PFS 7.4 vs 1.9 months, HR 0.34 (0.28–0.42). ORR 26.4% vs 4.1%. (ESMO 2026 LBA3, Jacob Sands; NEJM; data cutoff Jul 7, 2026) Grade ≥3 TEAEs 46.8% vs 40.6%. CRS 49.6%, grade 3 0.4%, no grade 4 or 5. ICANS 1.1%, none grade ≥3. (LBA3 abstract and slides) The first-line combination is investigational. Tarlatamab has full FDA approval for ES-SCLC that progressed on or after platinum chemotherapy (November 19, 2025). (KOL Pulse DeLLphi-305 page)
DeLLphi-305 overall survival. Jacob Sands, ESMO 2026 Presidential Symposium I, LBA3. Photo posted by
@HHorinouchi.
Physicians called it a new standard. Stephen V Liu was the invited discussant. Posts on his discussion and after it raised the attrition between induction and maintenance, access to tarlatamab at progression in the control arm, and global access.
Agreement and open questions
DeLLphi-305 - tarlatamab added to durvalumab after initial chemo-immunotherapy for small lung cancer essentially doubles survival. Hope for all cancers here, if the right target & treatment modality can be refined. Unquestionably a new standard for this disease. #ESMO2026
https://t.co/8ovQ2yB6fr
#ESMO26 Presidential 1
Excellent state-of-the art discussion on #Dellphi-305 by the 1@only @StephenVLiu
emphasizing on:
➡️ 1L maintenance Tarla setting a new SoC with a mOS of>20 months
❓High attrition rate from induction to maintenance, need for earlier TCE ( Dellphi-312)
❌Only 19% of pts in control arm received 2L Tarla post-progression reflecting access hurdles
✅ Global access to Tarla will make innovation meaningful for our patients
@@myESMO #ESMOAmbassadors
View post on X ↗
Median OS almost 2 years in ES-SCLC with Tarlatamab+Durvalumab maintenance = practice changing!
➡️ Challenge remains implementing Tarlatamab broadly + equitably so that all patients with ES-SCLC may benefit from this revolutionary therapy.
@OncoAlert #ESMO26 @NEJM
https://t.co/Ug6TxnAd1J The critical perspective
DeLLphi-305 delivered an unprecedented OS improvement (21.1 vs 12.7 mo, HR 0.42) for patients receiving tarlatamab + durvalumab, compared to durvalumab alone, in 1L maintenance after chemoIO induction for ES-SCLC. Studies like these provide renewed hope.
However, this data brings forth multiple concerns regarding international access to care, interpretation of contribution of parts, patient selection, and sequencing.
[...]
1️⃣ Equitable access to cross-over: at time of POD, only 12.2% of ITT population in the durvalumab arm (34/278) and 18.9% (34/179) of those who received subsequent anti-cancer therapies had access to tarlatamab.
Read the full post on X ↗ NSCLC: targeted therapy
KRASCENDO-1: divarasib vs sotorasib or adagrasib in KRAS G12C NSCLC
Phase 3 head-to-head, N=338, previously treated advanced KRAS G12C-mutant NSCLC. Divarasib (Roche/Genentech) vs investigator’s choice of sotorasib (n=156) or adagrasib (n=15). PFS by BICR 9.8 vs 5.7 months, HR 0.58 (95% CI 0.44–0.76), P<0.0001. OS 17.7 vs 12.0 months, HR 0.56 (0.41–0.78), P=0.0005. Confirmed ORR 58.4% vs 32.3%. Grade 3–4 treatment-related AEs 24.6% vs 34.5%; treatment-related AEs leading to discontinuation 4.8% vs 11.7%. Median treatment duration was 11.3 vs 5.0 months. (ESMO 2026 LBA5 abstract, Ferdinandos Skoulidis; data cutoff May 19, 2026) Divarasib is investigational. Sotorasib and adagrasib hold FDA accelerated approvals in this setting. (KOL Pulse KRASCENDO-1 page) Ferdinandos Skoulidis presented it on October 25 in Presidential Symposium II, with Benjamin Besse as invited discussant.
KRASCENDO-1 results table from the LBA5 abstract (not a presented slide). Photo posted by
@M_Torasawa.
Physicians welcomed a randomized comparison within the KRAS G12C class. Before the abstract was released, the questions were the size of the gap and tolerability.
Head-to-head within one drug class
#ESMO26 LBA5
🚨 Krascendo-1 (Phase 3)
Divarasib vs sotorasib/adagrasib in KRAS G12C-mutant NSCLC after platinum chemotherapy and immunotherapy (n=338).
💊 91% of controls received sotorasib (only 9% adagrasib).
✅ mPFS: 9.8 vs 5.7 mo (HR 0.58; P<0.0001)
✅ mOS: 17.7 vs 12.0 mo (HR 0.56; P=0.0005)
✅ ORR: 58.4% vs 32.3%
🛡️ Safety
• G3–4 TRAEs: 24.6% vs 34.5%
• TRAE-related discontinuation: 4.8% vs 11.7%
• Median treatment duration: 11.3 vs 5.0 mo
Impressive head-to-head PFS and OS benefits, with fewer severe TRAEs despite longer treatment exposure.
#LCSM
View post on X ↗
@myESMO @LungCancerRx @OncoAlert @oncodaily 4/ Krascendo 1 (LBA5), Oct 25, 16:30 CET
Divarasib vs sotorasib or adagrasib, pretreated KRAS G12C NSCLC.
Roche reports PFS + OS wins. How wide is the gap within the G12C class, and at what tolerability?
@LungCancerRx @OncoAlert @oncodaily
https://t.co/bq3FpEdrj8
2⃣Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC.
Given the evolution of KRAS G12Ci in this space, what is notable here is the direct prospective comparison to current KRAS G12Ci (adagrasib / sotorasib). Looking forward to ascertain magnitude of potential benefit and safety differences.
Read the full post on X ↗ KRASCENDO-1 population and design, from the invited discussion by Benjamin Besse. ESMO 2026, LBA5. Photo posted by
@StephenVLiu.
After the presentation, physicians called divarasib a new standard in this setting. The invited discussant, Benjamin Besse, criticized the lack of crossover.
After the presentation
Brilliant discussion from Dr. @BenjaminBesseMD at #ESMO26 on the Krascendo 1 study of divarasib vs sotorasib/adagrasib. Rightly points out lack of crossover in a study with a PFS endpoint as unjust. Excellent points all around. #ESMOAmbassadors
https://t.co/AZp29NMYLI
💊 Sotorasib and adagrasib were fundamental proof of concept drugs approved for a clear unmet need even none of them never demonstrated overall survival benefit.
🤯 Today those drugs are part of the past in oncology history.
Divarasib improve ORR, PFS and OS in previously treated KRAS G12C mutant NSCLC with a better safety profile in Krascendo1 Ph3 randomized clinical trial.
Kudos to @Roche to conduct a F2F trial.
#ESMO26 #LCSM
View post on X ↗ SAFFRON: osimertinib + savolitinib after osimertinib in MET-driven EGFR-mutant NSCLC
Phase 3, N=338, EGFR-mutant NSCLC with MET overexpression (IHC 3+ in ≥90% of tumor cells) and/or amplification (≥10 copies by FISH) after osimertinib. Osimertinib + savolitinib (n=171) vs platinum–pemetrexed (n=167). PFS by BICR 7.6 vs 5.4 months, HR 0.55 (95% CI 0.42–0.72), P<0.001. OS 17.8 vs 12.9 months, HR 0.68 (0.50–0.91), P=0.010. Grade ≥3 treatment-related AEs 40% vs 52%; adverse events leading to discontinuation (any cause) 14% vs 8%. (ESMO 2026 LBA6 abstract, Shun Lu; data cutoff Jul 6, 2026) The combination is investigational in the US (FDA Fast Track). It is approved in China based on the SACHI trial. (KOL Pulse SAFFRON page) Shun Lu presented it on October 25 in Presidential Symposium II, with Natasha Leighl as invited discussant.
SAFFRON efficacy table from the LBA6 abstract (not a presented slide). Photo posted by
@M_Torasawa.
Physicians noted an OS benefit with an all-oral regimen. The questions were whether it becomes the standard after osimertinib and how patients are selected by MET testing.
A new option, and who qualifies
#ESMO26 | LBA6
🚨 SAFFRON (Phase 3)
Osimertinib + savolitinib vs platinum–pemetrexed in EGFRm/MET-high NSCLC after 1L/2L osimertinib (n=338).
🧬🔬 Stringent MET selection:
IHC 3+ in ≥90% of tumor cells and/or MET gene copy number ≥10 by FISH.
✅ mPFS: 7.6 vs 5.4 mo (HR 0.55; P<0.001)
✅ mOS: 17.8 vs 12.9 mo (HR 0.68; P=0.010)
✅ mDoR: 9.7 vs 5.7 mo
💡PFS benefit was consistent across MET-OE and MET-AMP subgroups.
⚠️ Safety:
• Grade ≥3 TRAEs: 40% vs 52%
• TEAE-related discontinuation: 14% vs 8%
First global Phase 3 to demonstrate a significant OS benefit in MET-selected EGFRm NSCLC after osimertinib, supporting a new targeted treatment option.
#LCSM
View post on X ↗
ESMO 2026 Presidential 2 | SAFFRON Phase III:
Osimertinib + savolitinib vs platinum–pemetrexed in MET-overexpressed/amplified NSCLC progressing on osimertinib (n=338).
📊 Key results:
✅ mPFS: 7.6 vs 5.4 months (HR 0.55; p<0.001)
✅ mOS: 17.8 vs 12.9 months (HR 0.68; p=0.010)
✅ Median DoR: 9.7 vs 5.7 months
⚠️ Grade ≥3 treatment-related AEs: 40% vs 52%
⚠️ Treatment discontinuation due to AEs: 14% vs 8% (all-causality)
🔥 45% reduction in risk of progression and 32% reduction in risk of death!
A significant OS benefit with an all-oral, chemotherapy-free combination.
Is osimertinib + savolitinib the new standard for MET-driven resistance after osimertinib?
@OncoAlert @myESMO
#ESMO26 #LungCancer #EGFR #NSCLC
View post on X ↗
@myESMO @LungCancerRx @OncoAlert @oncodaily 2/ SAFFRON (LBA6), Oct 25, 16:54 CET
Osimertinib + savolitinib vs platinum–pemetrexed, EGFRm MET-high NSCLC after osimertinib.
Sponsors report PFS + OS wins. How big, and which MET IHC/FISH cutoff selects patients?
@LungCancerRx @OncoAlert @oncodaily
https://t.co/a1jM7oyRXW SAFFRON overall survival. Shun Lu, ESMO 2026, LBA6. Photo posted by
@Alfdoc2.
After the presentation, the discussion turned to patient selection: whether MET testing by IHC alone finds the right patients.
After the presentation
Excellent discussion from Natasha Leighl contextualising Saffron study. MET amplification defined by previous Savannah study. Is IHC enough - yes!Control arm performs as expected, but note that MET is a poor prognostic marker
But less than a third have MET 3+.
#ESMO26 #LCSM
https://t.co/NuBYbao35t
SAFFRON provides further evidence for 2 key concepts:
1. Continue osimertinib post-progression.
2. Target MET overexpression.
My main concern with this particular approach is patient selection. How many patients have c-MET IHC 3+ >90%?
@EGFRResisters @myESMO #ESMO26
https://t.co/YCJKZAZcuD PACE-LUNG: adding chemotherapy when EGFR ctDNA persists on osimertinib
Single-arm Phase 2 trial (LBA73, Martin Sebastian, Rapid oral 1, October 24). Patients with EGFR-mutant NSCLC and plasma EGFR ctDNA still detectable at week 3 of first-line osimertinib received added platinum–pemetrexed. The ctDNA-guided strategy is investigational. Source: LBA73 abstract, ESMO 2026 program.
PACE-LUNG patient disposition and liquid biopsy results. Martin Sebastian, ESMO 2026, LBA73. Photo posted by
@StephenVLiu.
Physicians agreed the approach is feasible. The debate was the lack of a comparator and whether ctDNA clearance is prognostic or predictive.
Feasible, but is it predictive?
#ESMO26 Dr. Martin Sebastian presents PACE-LUNG: phase II study of osimertinib monotherapy for EGFR NSCLC with ctDNA at 3w and if positive, add 4 cycles of chemotherapy. 72/255 were ctDNA positive at 3w. mPFS 17.8m and OS 31.5m from start of osi - no comparator but encouraging.
https://t.co/6VbL02UEJ5
Thoughtful trial: PACE-LUNG demonstrates that ctDNA-guided treatment intensification is feasible and results in a 17.8 m PFS that compares favorably with historical studies. @myESMO #ESMO2026 @OncoAlert
https://t.co/XEcwq2DtIs
PACE lung: treatment escalation in ctDNA non clearers. Would be nice to know more about the ctDNA positive group co-mutations. #LCSM #ESMO26
https://t.co/s4U6B9csMH
ctDNA with 1L EGFRmut regimens
❓what does it tell us
❓what does it add
We already know:
🔸EGFR ctDNA +ve @ baseline = poorer prognosis
🔸 Clearing EGFR ctDNA with treatment = better prognosis
🔸 EGFR ctDNA -ve @ baseline = no additional benefit of chemo/osi or ami/laz over osi alone
PACE-Lung:
🔹ctDNA +ve at baseline
🔹If also ctDNA after 4wks on Osi, add chemo (x4 cycles)
🔹 mPFS = 17.8m [similar to FL2]
FLAURA-2:
🔹 Focus on ctDNA +ve at baseline popn
🔹Osi+chemo improves OS & PFS irrespective of ctDNA clearance
🔹ctDNA +ve at baseline is prognostic, not predictive
What do we know now?
🤔 If EGFR ctDNA -ve at baseline (20% popn), prognosis is better, and adding chemotherapy to osimertinib, or using ami/laz instead of osimertinib add little (no) benefit
🤔 If EGFR ctDNA +ve at baseline (80% popn), prognosis is worse. However, clearance or not of ctDNA does not help us refine treatments
🤔 If EGFR ctDNA +ve at baseline, osi+chemo or ami/laz is better than Osimertinib alone
Brilliant discussion by @LeXiuning
👏
#ESMO26 #LCSM
View post on X ↗
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NSCLC: radiotherapy, first-line immunotherapy, ADCs, immunotherapy duration and supportive care
SARON: consolidation radiotherapy for synchronous oligometastatic NSCLC
Randomized trial of systemic therapy with or without consolidation radiotherapy (2613O, Fiona McDonald, Proffered paper 1, October 25). Source: 2613O abstract, ESMO 2026 program.
SARON overall survival. Fiona McDonald, ESMO 2026, 2613O. Photo posted by
@DrRiyazShah.
Physicians focused on better local control and PFS without an OS difference, the radiotherapy techniques used, and how the results apply to patients treated with SABR to all sites.
Local control vs survival
SARON; 1-5 mets; 6-8w induction SACT; P2 study:n140; 10y recruitment; SACT used evolved to include IO but valences in arms; no difference in OS; PFS 0.64HR but no difference new sites of disease #ESMO26 @BTOGORG #LCSM
Great presentation @fifimcdrmh
https://t.co/y6hzhSquQG
Congrats to the SARON investigators! Important randomized data for a question we face all the time. 👏
Consolidation RT improved local control and PFS, but no OS benefit demonstrated: HR 0.99 (95% CI 0.63-1.55).
The RT details caught my eye. Of 62 pts who received RT, 51 had conventional treatment to the primary and only 11 had primary SABR. About 53% of the full cohort had N2/3 disease.
Side note: in the separate 13-pt ESTRO safety substudy, the most common schedules were 55 Gy/20 fx to the primary (10/13 pts) and 27 Gy/3 fx to thoracic mets (4/14 lesions). Those are substudy doses, not the dose distribution for the whole trial.
Curious how pts who actually received SABR to all sites did. That would be exploratory, but I'd like to see the dose/volume details and patterns of failure before generalizing these results to patients receiving total consolidation.
Looking forward to the full paper! #ESMO26 #radonc
https://t.co/3AtnSapEMk
🫁 Better local control does not always mean longer survival.
@OncoAlert
At #ESMO26, the randomized phase II SARON trial tested whether adding consolidation radiotherapy to first-line systemic therapy could improve outcomes in synchronous oligometastatic, AGA-negative #NSCLC.
📊 n=140
➡️ Median PFS: 13.9 vs 8.9 months
HR 0.64, p=0.03
➡️ 12-month local failure: 13.0% vs 39.5%
p<0.01
➡️ Median OS: 31.0 vs 28.0 months
HR 0.99, p=0.95
⚠️ Grade ≥3 AEs: 28.6% in both arms
🎯 Why this matters: consolidation RT clearly improved disease control and reduced local failure, but that did not translate into an OS benefit.
For me, this is a reminder that oligometastatic disease is not a single biological state. The value of local therapy may depend on patient selection, disease biology, timing, and whether control of visible disease can meaningfully alter the systemic course.
Excellent work presented by @fifimcdrmh.
Pinging @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @MartinReck2 @CharuAggarwalMD @peters_solange
#OncoAlert #ESMO26 #LungCancer #OligometastaticDisease #Radiotherapy #PrecisionOncology
View post on X ↗ After the presentation on October 25, physicians agreed on the improved local control and progression-free survival without an overall survival benefit. The open question was which patients gain enough from consolidation radiotherapy to justify it. Benjamin P. Levy was the invited discussant for SARON and PERSEE.
After the presentation
Presenting the UK’s SARON study Dr @fifimcdrmh to a full hall at #ESMO26
In patients with de novo oligometastatic mutation driver negative #NSCLC , consolidation radiotherapy to the primary and metastases improved PFS but no OS
No significant difference in QOL or AEs
Huge thanks to all the patients and trialists involved
View post on X ↗
#ESMO26 | SARON
RT improves local control and delays progression, but no survival benefit was demonstrated. There was no significant reduction in new distant metastases either.
https://t.co/PaP1tQXPlX
Better local control. Longer PFS. No demonstrated OS benefit.
SARON randomized 140 patients with synchronous oligometastatic NSCLC without actionable genomic alterations to systemic therapy ± radical radiotherapy.
• Primary OS endpoint NOT met: HR 0.99; P=0.95
• PFS: 13.9 vs 8.9 months; HR 0.64; P=0.03
• 12-month local failure: 13.0% vs 39.5%
• Grade ≥3 AEs: 28.6% in both groups
Importantly, 40% received chemotherapy alone.
Which patients gain enough from consolidation RT to justify treatment—and how does modern systemic therapy change that selection?
@StephenVLiu @CharuAggarwalMD @myESMO @OncoAlert
#SARON #ESMO26 #LCSM #RadOnc
View post on X ↗ PERSEE (GFPC 01-2020): pembrolizumab with or without chemotherapy in PD-L1-high NSCLC
Academic Phase 3 trial from the French GFPC group: pembrolizumab plus platinum-based chemotherapy vs pembrolizumab alone as first-line treatment for advanced NSCLC with PD-L1 ≥50% and no EGFR or ALK alterations (2614O, Chantal Decroisette, Proffered paper 1, October 25; invited discussant Benjamin P. Levy), published simultaneously in Annals of Oncology. The primary endpoint was progression-free survival by blinded central review; overall survival was a key secondary endpoint. Pembrolizumab alone and pembrolizumab plus chemotherapy are both FDA-approved first-line options in this setting; PERSEE compared them head to head. Source: 2614O abstract, ESMO 2026 program.
PERSEE primary endpoint, progression-free survival by blinded central review. Chantal Decroisette, ESMO 2026, 2614O. Photo posted by
@StephenVLiu.
Several physicians called PERSEE practice changing. The debate was over the control arm and overall survival. Alfredo Addeo asked whether pembrolizumab alone underperformed compared with KEYNOTE-024; the presenter, Chantal Decroisette, replied that the arm was consistent with the updated KEYNOTE-024 results. Tom John noted that overall survival was not significant and said he would have liked it as the primary endpoint.
Did pembrolizumab alone underperform? A thread with the presenter
@StephenVLiu @HHorinouchi @decroisette @Annals_Oncology Very disappointed to see how poorly Pembro performed in the standard arm. Even in very high PD-L1 the mPFS was only 7.1 months which is a lot lower of the 10 months seen in Keynote 024
View post on X ↗
@Alfdoc2 @StephenVLiu @HHorinouchi @Annals_Oncology The update of the mPFS of the KN 024 is 7.7 months ( not 10 months) in the update datas ( Reck JCO 2021) . So our Pembrolizumab arm is consistent to KN 024 outcomes .
View post on X ↗ Practice changing?
‼️ In first line treatment of advanced PD-L1 ≥50% NSCLC, PERSEE demonstrates a significant improvement of PFS with pembro-CT compared to pembro monotherapy regardless of PDL1 level of (over)expression. Practise changing trial. @myESMO @OncoAlert #ESMO26 👏👏👏 @decroisette
https://t.co/PXSKgrImYX
Practice changing PERSEE trial. Chemo/IO vs IO in PDL1>50%. Trial powered for PFS, which was positive regardless of PDL1. OS not significant but favours chemo. More AEs with chemo. Hard to ignore these results but would’ve liked OS as primary. #LCSM #ESMO26
https://t.co/Al6qUUeocy OptiTROP-Lung06: sac-TMT + pembrolizumab in PD-L1-negative non-squamous NSCLC
Randomized Phase 3 trial of sacituzumab tirumotecan (sac-TMT) plus pembrolizumab vs platinum–pemetrexed plus pembrolizumab, first line, in PD-L1-negative non-squamous NSCLC without EGFR or ALK alterations (LBA66, Caicun Zhou, Proffered paper 1, October 25; invited discussant Melissa L. Johnson), published in NEJM alongside the presentation. Sac-TMT is investigational in the US. Source: LBA66 abstract, ESMO 2026 program.
OptiTROP-Lung06 progression-free survival by BICR. Caicun Zhou, ESMO 2026, LBA66. Photo posted by
@StephenVLiu.
Before the presentation, the question was whether a TROP2 ADC can replace the platinum doublet alongside immunotherapy. After it, physicians pointed to the progression-free survival difference and the duration of response. They also raised immature overall survival and short follow-up, a trial population from China with global data still awaited, and access.
Before the presentation
#ESMO26 | OptiTROP-Lung06
PD-L1 <1% non-sq NSCLC:
Sac-TMT + pembro vs platinum/pem + pembro
🔹 PFS: 15 vs 5.7 mo (HR 0.49)
🔹 DoR: 13.6 vs 6.8 mo
🔹 OS: HR 0.58 (immature)
🔹 ≥G3 AEs: 47.6% vs 60.6%
Strong results vs contemporary chemo-IO.
https://t.co/mT1aoETKPQ
@myESMO @LungCancerRx @OncoAlert @oncodaily 5/ OptiTROP-Lung06 (LBA66), Oct 25, 10:53 CET
Sac-TMT + pembro vs chemo + pembro, 1L PD-L1-negative nonsquamous NSCLC.
PFS met per Kelun-Biotech. Can a TROP2 ADC replace the platinum doublet alongside IO?
@LungCancerRx @OncoAlert @oncodaily
https://t.co/XWMc6SJ3gy After the presentation
Zhou: Optitrop-Lung06 chemo/io vs sacTMT/Pembro in PDL1 neg. Impressive PFS difference. Similar second line use. Deeper responses and double duration of response. Less tox except more stomatitis.
Access is a major issue!
#LCSM #ESMO26
https://t.co/Rqm8vvYalR
🫁 #ESMO2026 OptiTROP-Lung06: sac-TMT + pembro vs chemo + pembro in PD-L1-negative NSCLC in china.
High never smoker (30%) and male (60%) popn.
Promising PFS: 15.0 vs 5.7m (HR 0.49). OS immature.
Global data awaited
Sac-TMT is also in clinical trials at @NHSBartsHealth
https://t.co/xL5qviAYhn
The response rates are close. The durability is not.
OptiTROP-Lung06: first-line, PD-L1-negative, EGFR/ALK-negative nonsquamous NSCLC.
Sac-TMT + pembrolizumab vs chemotherapy + pembrolizumab:
• Primary BICR-PFS: 15.0 vs 5.7 months; HR 0.49; P<0.0001
• ORR: 50.2% vs 47.3%
• Median response duration: 13.6 vs 6.8 months
• Grade ≥3 TEAEs: 47.6% vs 60.6%
OS is immature, and median follow-up is only 9.7 months.
Could replacing conventional chemotherapy with a TROP2 ADC improve the durability of first-line disease control? Longer follow-up will be crucial.
@StephenVLiu @CharuAggarwalMD @myESMO @OncoAlert
#OptiTROPLung06 #ESMO26 #LCSM
View post on X ↗ OptiTROP-Lung04: sac-TMT vs platinum chemotherapy in EGFR-mutant NSCLC after EGFR-TKI
Trending on Day 3: almost all of the OptiTROP-Lung04 physician posts came on October 25, after the presentation. It is a different trial from OptiTROP-Lung06 above. OptiTROP-Lung04 is a randomized Phase 3 trial of sac-TMT monotherapy (Kelun-Biotech; licensed to MSD outside China) vs pemetrexed plus platinum, followed by pemetrexed maintenance, in locally advanced or metastatic EGFR-mutant NSCLC that progressed on EGFR-TKI therapy. ESMO 2026 reported the prespecified final overall survival analysis (LBA67, Wenfeng Fang, Proffered paper 1, October 25; invited discussant Melissa L. Johnson); interim results were published in NEJM in 2025. In China, the NMPA approved sac-TMT for EGFR-mutant NSCLC after EGFR-TKI therapy in October 2025, based on this trial. Sac-TMT is investigational in the US and elsewhere outside China. Source: LBA67 abstract, ESMO 2026 program.
OptiTROP-Lung04 final overall survival. Wenfeng Fang, ESMO 2026, LBA67. Photo posted by
@StephenVLiu.
Physicians agreed the overall survival benefit was impressive. The debate was over how to read it: Antonio Calles noted the p value is nominal, Adam Januszewski noted the trial enrolled patients in China and said global data will be important, and Tom John flagged nuances, including subsequent therapies, toxicity and no osimertinib in either arm, while calling the benefit hard to ignore. Neither the presenter nor the discussant had posted about it on X when this was written.
Impressive, with nuances
#ESMO26 Dr. Wenfeng Fang presents update on OptiTROP-Lung04: sac-TMT (TROP2 ADC) vs platinum + pemetrexed in EGFR mutant NSCLC post TKI therapy. OS favors sac-TMT: 25.9m vs 17.4m, HR 0.69 (even better if 1L was 3G TKI). #ESMOAmbassadors
https://t.co/5kuwemKsBj
💥 Sac-TMT hits OS benefit in previously TKI-treated EGFR mutant lung cancer compared to standard carbo-pem chemotherapy (although nominal p value) Another option in a rapid evolving scenario. #ESMO26 #LCSM
https://t.co/GhOHXVjCS8
🫁 #ESMO2026 OptiTROP-Lung04: Final OS analysis of sac-TMT vs chemotherapy in EGFRm NSCLC after EGFR-TKI progression.
🇨🇳 Chinese-only phase III (n=376)
📈 OS: 25.9 vs 17.4m (HR 0.69)
Impressive OS benefit. Global data will be important
2nd line EGFR setting v. complex
https://t.co/eDX7HtQF9n
Fang: SacTMT in EGFR OptiTroplung04. Note no Osi in either arm. OS primary endpoint. Impressive benefit, but there are some nuances. Less subsequent therapies, more tox in Sac arm. But 7month benefit hard to ignore these results
#LCSM #ESMO26
https://t.co/G2ddmz7h8b Context: the LBA67 abstract and the presented study design slide list overall survival as the key secondary endpoint; the primary endpoint was progression-free survival by blinded independent central review.
SigVie-002: sigvotatug vedotin vs docetaxel misses its primary endpoint
Phase 3 trial of sigvotatug vedotin (Pfizer), an integrin beta-6-directed ADC, vs docetaxel in previously treated non-squamous NSCLC (LBA68, Solange Peters, Proffered paper 1, October 25). Sigvotatug vedotin did not significantly improve overall survival, the primary endpoint, in the overall population, and secondary endpoints including progression-free survival were not significantly improved. The abstract reports favorable trends in a post hoc second-line subgroup, mostly patients without actionable genomic alterations, and no clear relationship between integrin beta-6 expression and efficacy. The authors said the results support further development in combination with pembrolizumab or a PD-1/VEGF bispecific in earlier settings. Sigvotatug vedotin is investigational and not FDA approved. Source: LBA68 abstract, ESMO 2026 program.
SigVie-002 primary and secondary endpoints in the overall population. Solange Peters, ESMO 2026, LBA68. Photo posted by
@StephenVLiu.
Physicians agreed the trial was negative. Antonio Calles called it completely negative, and Noemi Reguart said the challenge of beating docetaxel with ADCs in second line continues. Stephen V Liu saw some signal in driver-negative patients in second line; the abstract labels that subgroup analysis post hoc.
A negative trial, and a post hoc signal
❌Completely negative phase III trial of
sigvotatug vedotin (SV) vs docetaxel in previously treated NSCLC.
🔬 Explorative integrin beta-6 (IB6) expression not predictive of efficacy.
#ESMO26 #LCSM
https://t.co/EItPWw0TSu
Another negative phase III trial in pretreated NSCLC! ❌ SigVie-002 sigvotatug vedotin vs docetaxel failed to meet its primary OS endpoint in non-squamous NSCLC. @peters_solange. The challenge of beating docetaxel with ADCs in 2L continues! #ESMO26 #LungCancer
https://t.co/rmBBg7zn2E
#ESMO26 Dr. @peters_solange presents phase 3 study of sigvotatug vedotin (SV, integrin beta-6 ADC) vs docetaxel in previously treated non-squamous NSCLC. No difference in survival. Some signal in driver-negative NSCLC in 2L setting (vs 3L). #ESMOAmbassadors
https://t.co/t2NW9Ye0xR
Disappointing results from SigVie-002 at #ESMO26.
@peters_solange presents the phase III trial of sigvotatug vedotin vs docetaxel in previously treated advanced nonsquamous NSCLC.
No OS benefit: 11.9 vs 11.5 months (HR 0.93; p=0.226)
No significant PFS improvement: 4.7 vs 4.2 months (HR 0.84)
Exploratory analyses showed no clear efficacy trend according to integrin β6 (IB6) expression.
Another reminder that promising ADC biology does not always translate into clinical benefit in phase III trials.
#ESMOAmbassadors #ESMO26 #LungCancer #NSCLC #ADC
View post on X ↗ DIAL (IFCT-2103): stopping immunotherapy at 6 months
Phase 2 part of the phase 2–3 IFCT-2103 DIAL trial: continuing pembrolizumab (± pemetrexed) up to 2 years vs observation (± pemetrexed) in metastatic NSCLC with disease control at 6 months (2618RO, Anne-Claire Toffart, Rapid oral 2, October 25). Stopping immunotherapy at 6 months is an investigational strategy. Source: 2618RO abstract, ESMO 2026 program.
DIAL overall survival. Anne-Claire Toffart, ESMO 2026, 2618RO. Photo posted by
@DrRiyazShah.
De-escalation
#ESMO26 Dr. @ToffartC with phase II IFCT-2103 DIAL trial. After 6m chemo-pembro, pts w/o progression randomized to complete 2y of therapy or stop IO (cont maintpemetrexed). Similar 18m & 24m survival & less toxicity with shorter IO course. Phase III ongoing #ESMOAmbassadors
https://t.co/FvZgv6Q7t5
IFCT 2103 DIAL; lovely and provocative ; after 6/12 chemo io….no difference between continuation and de-escalation arms….. #ESMO26
https://t.co/cI2LaUL7y5 COCOON: preventing skin toxicity with amivantamab + lazertinib
New non-randomized cohorts of the COCOON Phase 2 trial tested simplified dermatologic prophylaxis with subcutaneous amivantamab plus lazertinib, including a lazertinib lead-in (2700RO, Byoung Chul Cho, Rapid oral 1, October 24). Intravenous amivantamab plus lazertinib is FDA approved for first-line NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Source: 2700RO abstract, ESMO 2026 program.
COCOON primary endpoint by cohort. Byoung Chul Cho, ESMO 2026, 2700RO. Photo posted by
@tnewsomdavis.
Physicians agreed the regimen is easier to tolerate. The open question is whether efficacy holds.
Tolerability vs efficacy
‘New’ COCOON:
Reducing adverse events with Amivantamab/Lazertinib
👉 Simplified skin care regimen (x6m oral tetracycline, ceramide cream, oral zinc)
👉 Step up dosing: Lazer x4wks BEFORE Ami starts
✅ Combined approach reduces all grade dermatological adverse events (HR 0.31) @ 3m
✅ No Gr2+ cutaneous adverse events @ 4m
✅ Gr2+ scalp AE just 3%
🤔 I have no problem starting Lazer 1 month before Ami, if it makes combination much more tolerable. (With FLAURA2 we already start Osimertinib before chemo, whilst we wait for chemotherapy unit slot)
🤔 Need PFS data to make sure new COCOON does not impact on efficacy, but I doubt it will
🤔 Pragmatic way make this regimen easier, which is needed because it is challenging
#ESMO26 #LCSM
View post on X ↗
🦋 Making amivantamab + lazertinib safer: new COCOON data at #ESMO26!
New results from the COCOON study suggest that simplified dermatologic prophylaxis, combined with subcutaneous amivantamab + lazertinib, may substantially reduce treatment-related skin toxicity in first-line EGFR-mutant NSCLC. Key findings:Grade ≥2 dermatologic AEs: 39% with standard initiation vs 18% with a one-cycle lazertinib lead-in. Simplified prophylaxis appears to provide protection comparable to the original COCOON regimen. Sc markedly reduces IRR reactions.The new cohorts were non-randomized, and the comparison between initiation strategies was exploratory.
Personal take: No doubt about less ami less tox. Question is if efficacy remains the same in the era of Flaura2?!
#ESMOAmbassador #ESMO26 #LungCancer #NSCLC #EGFR #COCOON #Oncology #CancerResearch
View post on X ↗ More Day 3 lung presentations
Four more lung presentations on October 25 drew physician posts. One post is shown for each. All four regimens are investigational. Source: ESMO 2026 program.
ROSETTA Lung-107: pumitamig + docetaxel after chemo-immunotherapy
Global Phase 2, open-label trial of pumitamig, a PD-L1 × VEGF-A bispecific antibody, plus docetaxel in metastatic NSCLC after chemo-immunotherapy; first data (LBA76, Byoung Chul Cho, Rapid oral 2, October 25).
Reaction
#ESMO26 Dr. Byoung Cho @cbcbc1971 presents ROSETTA Lung-107: phase 2 pumitamig + docetaxel post-chemoIO in NSCLC. Reassuring safety profile including in squamous NSCLC. In squamous, RR 57%, DCR 100%. In non-squamous, RR 30%, DCR 87%. mPFS 6.9m and 6m PFS 63%. #ESMOAmbassadors
https://t.co/k4VgPE4tRq Combi-TED: OSE2101 vaccine with docetaxel or nivolumab in second line
Randomized Phase 2 trial of the therapeutic cancer vaccine OSE2101 plus docetaxel or plus nivolumab, vs docetaxel, as second-line therapy for metastatic NSCLC after first-line chemo-immunotherapy (2661RO, Federico Cappuzzo, Rapid oral 2, October 25).
Reaction
#ESMO26 Dr. @FedericoCappuz1 presents phase II randomized trial of therapeutic cancer vaccine OSE2101 with docetaxel or with nivolumab vs docetaxal. Very reassuring safety profile of vaccine; 1y OS rate superior with both OSE2101 combinations. Phase III ARTEMIA trial ongoing.
https://t.co/nHc1PCaeis SUNRAY-01 and LOXO-RAS-20001: first-line olomorasib + chemo-immunotherapy in KRAS G12C NSCLC
Updated pooled results of first-line olomorasib plus chemo-immunotherapy in KRAS G12C-mutant NSCLC from the LOXO-RAS-20001 and SUNRAY-01 trials (2652RO, Marcelo V. Negrao, Rapid oral 2, October 25).
Reaction
#ESMO26 Dr. @mvnegrao with pooled data on 1L olomorasib + chemo-IO in KRAS G12C NSCLC from LOXO-RAS-20001 and SUNRAY-01. RR 62%, mDOR 14.5m, mPFS 11.6m, safety shows TRAEs leading to d/c in 7.8% of gen pop. #ESMOAmbassadors
https://t.co/GAvfqPnz2z NeoCOAST-2: ctDNA clearance in a perioperative platform trial
Association of ctDNA clearance with clinical outcomes in the global platform Phase 2 perioperative NeoCOAST-2 trial in resectable NSCLC (4244RO, Tina Cascone, Rapid oral 1: Basic science and translational research, October 25), published simultaneously in Nature.
Reaction
Now in Nature w simultaneous presentation #ESMO26 #NeoCOAST2 ! 1st platform neoadjuvant trial to associate tumor agnostic ctDNA dynamics w pCR & EFS! Privileged to be part of this effort led by Drs. Lara McGrath & Tina Cascone! Paper/slides below! 1/ #lcsm
https://t.co/o7nmQfvLsJ KOL Voices: lung cancer
The top 10 physicians in the Lung tab of the ESMO 2026 Top KOLs leaderboard. One line from each, verbatim and linked, with the trial it is about.
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Riyaz Shah @DrRiyazShah · 13.3K impressions · 24 posts - 8
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What’s yet to come: lung cancer, October 26–27
Times are Madrid time. Results are not out until each presentation.
| When | Session | Trial or abstract | Presenter |
|---|
| Mon Oct 26, 08:30 | Proffered paper 2: NSCLC, metastatic | LBA69 SANOVO (Phase 3): savolitinib or placebo plus osimertinib, treatment-naive EGFR-mutant, MET-overexpressed NSCLC | Yi-Long Wu |
| Mon Oct 26, 08:40 | Proffered paper 2: NSCLC, metastatic | 2615O: dalmelitinib plus aumolertinib vs platinum-based chemotherapy, MET amplification after EGFR TKI (randomized Phase 3) | Ziming Li |
| Mon Oct 26, 08:50 | Proffered paper 2: NSCLC, metastatic | Invited discussant, LBA69 and 2615O | Rebecca Heist |
| Mon Oct 26, 09:14 | Proffered paper 2: NSCLC, metastatic | LBA71 PANKU-Lung01 (Phase 3): iza-bren in EGFR-mutant non-squamous NSCLC after a third-generation EGFR TKI | Li Zhang |
| Mon Oct 26, 09:24 | Proffered paper 2: NSCLC, metastatic | LBA72 HERON-Lung01 (Phase 3, interim analyses): ruzaltatug rezetecan (HER3-directed ADC) vs platinum-based chemotherapy, EGFR-mutated NSCLC after EGFR TKI | Chongrui Xu |
| Mon Oct 26, 09:34 | Proffered paper 2: NSCLC, metastatic | Invited discussant, LBA71 and LBA72 | Simon Ekman |
| Mon Oct 26, 10:15 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | 3837RO: ABBV-706, a SEZ6-targeted ADC, in relapsed/refractory SCLC | Anne C. Chiang |
| Mon Oct 26, 10:20 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | 3816RO: SKB500, a B7-H3-targeted ADC, in ES-SCLC (Phase 1) | Haifeng Liu |
| Mon Oct 26, 10:35 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | LBA62 MDT-BRIDGE: ctDNA clearance during neoadjuvant treatment, resectable/borderline resectable stage IIB-IIIB NSCLC | Jonathan Spicer |
| Mon Oct 26, 10:40 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | LBA65 CTONG 1804 part 3: surgical conversion after induction chemoimmunotherapy, stage III NSCLC | Yi Pan |
| Mon Oct 26, 10:45 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | 2574RO LungMate-014: neoadjuvant toripalimab plus chemotherapy with or without tifcemalimab, stage III NSCLC | Peng Zhang |
| Mon Oct 26, 11:02 | Rapid oral: Non-metastatic NSCLC and other thoracic malignancies | 4155RO THRIVE: rivoceranib in pretreated thymic epithelial tumors; 4156RO iTHYM: ivonescimab plus chemotherapy in thymic carcinoma; 4158RO: MTAP loss in mesothelioma | Sehhoon Park; Xue Hou; Sylvie Lantuejoul |
| Mon Oct 26, 14:45 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | 3808O DeLLphi-304: extended overall survival follow-up, tarlatamab in previously treated SCLC | Charles M. Rudin |
| Mon Oct 26, 14:55 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | 3809O ASTRIDE: serplulimab or atezolizumab plus chemotherapy in US patients with ES-SCLC | David R. Gandara |
| Mon Oct 26, 15:23 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | LBA64 Neotorch final analysis: perioperative toripalimab plus chemotherapy, resectable stage II-III NSCLC | Shun Lu |
| Mon Oct 26, 15:33 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | 2519O KEYNOTE-671: biomarkers and efficacy of perioperative pembrolizumab | Marina C. Garassino |
| Mon Oct 26, 15:43 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | 2511O PEARLS/KEYNOTE-091: final analysis of adjuvant pembrolizumab | Mary E. O’Brien |
| Mon Oct 26, 15:53 | Proffered paper: Non-metastatic NSCLC and other thoracic malignancies | Invited discussant, LBA64, 2519O and 2511O | Jordi Remon Masip |
| Tue Oct 27, 09:40 | Scientific Congress Highlights 2 | Congress highlights: NSCLC, metastatic | Patrick M. Forde |
| Tue Oct 27, 10:00 | Scientific Congress Highlights 2 | Congress highlights: Non-metastatic NSCLC and other thoracic malignancies | Pilar Garrido Lopez |
DeLLphi-304 background: DeLLphi-304 trial page. The ESMO 2026 trials page adds physician posts as these sessions happen.
FAQ
Which lung cancer trials did physicians discuss most at ESMO 2026?
By physician posts on X on October 23-25, DeLLphi-305 led with 102 posts from 73 physicians, followed by OptiTROP-Lung06 (24), PERSEE (20), SARON (15), OptiTROP-Lung04 (12), KRASCENDO-1 (10) and SigVie-002 (10).
Is OptiTROP-Lung04 the same trial as OptiTROP-Lung06?
No. OptiTROP-Lung04 compared sac-TMT alone with platinum-pemetrexed chemotherapy in EGFR-mutant NSCLC after EGFR-TKI therapy; ESMO 2026 reported its final overall survival analysis (LBA67). OptiTROP-Lung06 compared sac-TMT plus pembrolizumab with chemotherapy plus pembrolizumab as first-line treatment for PD-L1-negative non-squamous NSCLC (LBA66). Sac-TMT is approved in China for EGFR-mutant NSCLC after EGFR-TKI therapy and is investigational in the US.
Did SigVie-002 meet its primary endpoint?
No. Sigvotatug vedotin did not significantly improve overall survival, the primary endpoint, vs docetaxel in previously treated non-squamous NSCLC (ESMO 2026 LBA68). Trends in a second-line subgroup came from a post hoc analysis. Sigvotatug vedotin is investigational.
What did DeLLphi-305 show?
Adding tarlatamab to durvalumab as first-line maintenance in extensive-stage small cell lung cancer improved median OS from 12.7 to 21.1 months (HR 0.42, 95% CI 0.32-0.54) at a prespecified interim analysis (ESMO 2026 LBA3). The first-line combination is investigational; tarlatamab is FDA approved after platinum chemotherapy.
What did KRASCENDO-1 show?
In previously treated KRAS G12C-mutant NSCLC, divarasib improved PFS (9.8 vs 5.7 months, HR 0.58) and OS (17.7 vs 12.0 months, HR 0.56) vs sotorasib or adagrasib in the ESMO 2026 LBA5 abstract (data cutoff May 19, 2026). Divarasib is investigational.
Is osimertinib plus savolitinib approved in the US?
No. The combination is investigational in the US (FDA Fast Track). In SAFFRON (ESMO 2026 LBA6 abstract), it improved PFS (HR 0.55) and OS (HR 0.68) vs platinum-pemetrexed after osimertinib in MET-overexpressed and/or amplified EGFR-mutant NSCLC.
Which lung cancer sessions are still ahead at ESMO 2026?
On October 26: SANOVO, PANKU-Lung01 and HERON-Lung01 in the metastatic NSCLC proffered paper session; MDT-BRIDGE ctDNA and SCLC ADC rapid orals; DeLLphi-304 extended OS, ASTRIDE, Neotorch final analysis, KEYNOTE-671 biomarkers and PEARLS/KEYNOTE-091 final analysis. On October 27: lung congress highlights by Patrick M. Forde and Pilar Garrido Lopez.
Related ESMO 2026 pages