ASCO 2026 Plenary: RASolute 302 — Daraxonrasib Nearly Doubles Survival in Metastatic Pancreatic Cancer, First RAS Inhibitor to Demonstrate Overall Survival Benefit (NEJM)

In what many oncologists called the most consequential cancer trial result of the decade, the Phase 3 RASolute 302 trial — presented at the ASCO 2026 Plenary Session by Dr. Brian Wolpin (Dana-Farber Cancer Institute) and simultaneously published in The New England Journal of Medicine — demonstrated that daraxonrasib (RMC-6236; Revolution Medicines) nearly doubles overall survival in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). The trial enrolled 500 patients randomized to daraxonrasib versus investigator's choice cytotoxic chemotherapy. In the primary KRAS G12-mutant population (and the intent-to-treat population), median overall survival was 13.2 months with daraxonrasib versus 6.6–6.7 months with chemotherapy (HR 0.40, 95% CI 0.30–0.54; p<0.0001) — a 60% reduction in the risk of death. Median PFS was 7.3 vs. 3.5 months (HR 0.45; p<0.0001). Objective response rate was 33.2% vs. 11.8%. Critically, the safety profile was substantially better than chemotherapy: Grade 3+ adverse events in 43.6% (daraxonrasib) vs. 57.5% (chemotherapy); treatment discontinuations 1.2% vs. 11.2%. Daraxonrasib is an oral once-daily multi-selective RAS(ON) inhibitor targeting KRAS G12C, G12D, G12V, and other oncogenic RAS mutations. KRAS mutations drive approximately 90% of all pancreatic cancers. Pancreatic cancer — long considered undruggable at the RAS level — kills approximately 54,000 Americans and 460,000 people globally per year with a 5-year survival rate of approximately 12%. The RASolute 302 result received a standing ovation at the ASCO plenary. The FDA had already authorized an Expanded Access Protocol allowing patients access outside of clinical trials.