And just like that, adagrasib + cetuximab is no longer FDA approved for KRAS G12C colorectal cancer. The accelerated approval was officially withdrawn September 1 after KRYSTAL-10 failed to confirm benefit. We talked about KRYSTAL-10 when it was presented earlier this year. The phase III randomized 461 patients in 2L to adagrasib + cetuximab vs chemotherapy ± VEGF inhibition. It missed both primary endpoints: ▪️PFS: 7.5 vs 8.1 months, HR 0.89
▪️OS: 21.6 vs 21.7 months, HR 0.83 Hard to argue with a negative phase III trial. But I still like the idea of a chemo free option. Response rate was 47% vs 16%. That could matter for some patients (like those who you need just a little more shrinkage to enable crative intent therapy). KRYSTAL-10 asked whether adagrasib + cetuximab was better than chemotherapy in 2L. It wasn’t. That doesn’t mean the concept of KRAS G12C + EGFR blockade was wrong. And it doesn’t mean there aren’t patients for which this isnt valuable. Anyone celebrating this should look themselves in the mirror; this is a tool that has just been removed from our arsenal. However, the FDA did exactly what the system is designed to do; pull back if the Ph III doesnt pan out after accelerated approval. @OncoAlert @TheGutOncLab @Onco_Nexus

🚨 This may be the most consequential oncology study of 2026. Yes, on par with daraxonrasib. At #ASCO26 we highlighted the 5-year KEYNOTE-942 data for the individualized mRNA cancer vaccine intismeran + pembrolizumab in resected high-risk melanoma. And the numbers were 👀 RFS HR 0.51 5-year RFS: 68.8% vs 49.1% DMFS HR 0.41 OS HR 0.47 (still immature) Amazing data. But 157 patients. Phase IIb. The big question: does it hold up in phase III? Apparently, yes. 🔥 INTerpath-001 randomized 1,137 patients with resected stage IIB-IV melanoma to intismeran + pembrolizumab vs pembrolizumab alone. At the prespecified interim analysis: ✅ RFS met ✅ DMFS met ✅ Statistically significant AND ✅ No new safety signals We don’t have the HRs yet. So some restraint until we see the actual data (also this is a press release, so grain of salt) But why is this such a big deal? Because this isn’t really about melanoma. 🧬 Sequence YOUR tumor 🎯 Identify YOUR neoantigens 💉 Manufacture a vaccine specifically for YOUR cancer 🦠 Train YOUR immune system to recognize it And now that approach has succeeded in a randomized phase III trial. This is actually personalized. And if this platform works across tumor types, the implications are enormous. Daraxonrasib may change how we treat RAS-driven cancers. INTerpath-001 may change how we think about cancer vaccines altogether. 2026 has been an amazing year for oncology advances. 🔥 merck.com/news/merck-and-mod… @OncoAlert @Onco_Nexus @TheGutOncLab