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)

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.

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.

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

Masahiro TORASAWA, MD. PhD. @M_Torasawa

thoracic oncologist, Juntendo University · Oct 25

#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 ↗

Aakash Desai @ADesaiMD

thoracic and phase 1 oncologist, UAB O'Neal Comprehensive Cancer Center · Oct 23

@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

View post on X ↗

Tejas Patil @TejasPatilMD

thoracic oncologist, University of Colorado Cancer Center · Oct 24

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 ↗

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

Stephen V Liu, MD @StephenVLiu

thoracic oncologist; chief of hematology/oncology, Georgetown; DeLLphi-305 discussant · Oct 25

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

View post on X ↗

Dr. Antonio Calles 🫁🚭 @Tony_Calles

medical oncologist, Hospital General Universitario Gregorio Marañón · Oct 25

💊 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.

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.

After the presentation, the discussion turned to patient selection: whether MET testing by IHC alone finds the right patients.

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.

Physicians agreed the approach is feasible. The debate was the lack of a comparator and whether ctDNA clearance is prognostic or predictive.

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.

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.

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.

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.

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

Alfredo Addeo MD @Alfdoc2

medical oncologist, Geneva University Hospitals · Oct 25

@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 ↗

chantal decroisette @decroisette

PERSEE presenter, ESMO 2026 (2614O) · Oct 25

@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 ↗

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.

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.

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.

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.

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.

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.

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.

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.

Physicians agreed the regimen is easier to tolerate. The open question is whether efficacy holds.

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).

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).

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).

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.

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.

1. 1
   Hidehito Horinouchi @HHorinouchi · 111.7K impressions · 124 posts

   on SAFFRON → “Post-Progression Re-biopsy Mandated”
2. 2
   Stephen V Liu, MD @StephenVLiu · 45.3K impressions · 37 posts

   on PERSEE (GFPC 01-2020) → “Addition of chemotherapy as done in PERSEE is a real win, even in ultra high.”
3. 3
   Masahiro Torasawa, MD, PhD @M_Torasawa · 34.8K impressions · 7 posts

   on KRASCENDO-1 → “Impressive head-to-head PFS and OS benefits, with fewer severe TRAEs despite longer treatment exposure.”
4. 4
   Enes Erul, MD @ErulEnes · 22.5K impressions · 4 posts

   on DeLLphi-305 → “The moment I saw the overall survival curves, I wanted to stand up and applaud!”
5. 5
   Alfredo Addeo, MD @Alfdoc2 · 22.2K impressions · 31 posts

   on SigVie-002 → “Another reminder that promising ADC biology does not always translate into clinical benefit in phase III trials.”
6. 6
   Patrick Forde @FordePatrick · 17.8K impressions · 8 posts

   on DeLLphi-305 → “Unquestionably a new standard for this disease.”
7. 7
   Riyaz Shah @DrRiyazShah · 13.3K impressions · 24 posts

   on DeLLphi-305 → “this is about the strongest data I’ve seen in this space.”
8. 8
   Giannis Mountzios @g_mountzios · 11.7K impressions · 5 posts

   on DeLLphi-305 → “Who would have imagined some years ago that median OS of SCLC would equal that of non-AGA NSCLC!”
9. 9
   Antonio Calles @Tony_Calles · 11.1K impressions · 22 posts

   on OptiTROP-Lung04 → “Another option in a rapid evolving scenario.”
10. 10
    Aakash Desai @ADesaiMD · 11.0K impressions · 10 posts

    on OptiTROP-Lung06 → “What must ADCs show to replace platinum?”

What’s yet to come: lung cancer, October 26–27

Times are Madrid time. Results are not out until each presentation.

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

• ESMO 2026 lung cancer slide library
• ESMO 2026 trials: physician posts by trial
• ESMO 2026 conference page
• DeLLphi-305 trial page
• KRASCENDO-1 trial page
• SAFFRON trial page
• DeLLphi-304 trial page
• SigVie-002 trial page
• PERSEE trial page