ESMO Day 3: 10 Highlights, from KRAS Wins to ADC Reality Checks
Head-to-head wins, survival gains and a reminder that promising modalities do not guarantee positive trials. ESMO Day 3 brought results across targeted therapies, ADCs and bispecific antibodies. Here are 10 highlights.
1. Roche raises the KRAS bar | $RHHBY
In Phase 3 Krascendo 1, KRAS G12C inhibitor divarasib improved median overall survival to 17.7 vs. 12.0 months against pooled sotorasib/adagrasib controls. Death risk fell 44%, with fewer treatment-related discontinuations.
2. Merck/Kelun challenges the chemotherapy backbone | $MRK
In Phase 3 OptiTROP-Lung06, TROP2 ADC sac-TMT + pembrolizumab delivered median PFS of 15.0 vs. 5.7 months against chemotherapy + pembrolizumab in first-line PD-L1-negative nonsquamous NSCLC. A 51% reduction in progression-or-death risk, although OS remains immature.
3. Ivonescimab’s survival story expands | $SMMT / Akeso
The PD-1×VEGF bispecific + chemotherapy beat durvalumab + chemotherapy in Phase 3 HARMONi-GI1: median OS 14.9 vs. 12.1 months, reducing death risk 25% in advanced biliary tract cancer. All 682 patients were enrolled in China.
4. SAFFRON tackles Tagrisso resistance | $HCM $AZN
The MET/EGFR inhibitor combination savolitinib + osimertinib improved median OS to 17.8 vs. 12.9 months against chemotherapy in Phase 3 SAFFRON. The result targets MET-driven resistance after osimertinib; a US NDA submission was also disclosed.
5. AstraZeneca’s gastric ADC delivers a mixed verdict | $AZN
In Phase 3 CLARITY-Gastric01, CLDN18.2 ADC sonesitatug vedotin doubled median OS to 10.0 vs. 5.0 months in the third-line-plus population. However, the trial missed its PFS co-primary endpoint.
6. Lilly moves KRAS targeting toward first-line treatment | $LLY
Olomorasib + chemoimmunotherapy achieved 62% confirmed responses in 77 patients, with median response duration of 14.5 months. These Phase 1/2 and Phase 3 safety lead-in data are uncontrolled; randomized SUNRAY-01 results are expected in 1H2027.
7. Pumitamig shows activity after immunotherapy | $BNTX $BMY
In Phase 2 ROSETTA Lung-107, the PD-L1×VEGF-A bispecific + docetaxel achieved 36.7% confirmed responses in 30 evaluable patients. Median PFS was 6.9 months across 50 treated patients, but follow-up remains short and there is no randomized comparator.
8. Pfizer’s lung ADC falls short | $PFE
In Phase 3 SigVie-002, integrin β6 ADC sigvotatug vedotin failed to significantly improve OS: 11.9 vs. 11.5 months against docetaxel. A numerical benefit in a post hoc second-line subgroup does not overturn the negative primary result.
9. J&J explores head-and-neck cancer | $JNJ
In Phase 1b/2 OrigAMI-4, amivantamab + pembrolizumab + carboplatin achieved 77% confirmed responses, including 14% complete responses, in a 22-patient subgroup excluding HPV-associated oropharyngeal cancer. Encouraging activity, with small numbers and no control arm.
10. Xencor brings a new T-cell engager target to kidney cancer | $XNCR
Phase 1 XmAb819, an ENPP3×CD3 bispecific, achieved 45.5% confirmed responses in 11 evaluable patients at 400 μg/kg. Safety remains central: grade ≥3 treatment-related adverse events occurred in 72.1% across the 68-patient expansion safety population.
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Article history:
First published 10/25/26 MD
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