Daraxonrasib Phase 1/2 Results Published in NEJM: 30% Response Rate in RAS-Mutant Metastatic Pancreatic Cancer

Dana-Farber Cancer Institute announced the simultaneous publication in the New England Journal of Medicine (doi: 10.1056/NEJMoa2505783) of full Phase 1/2 clinical data for daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, in 168 patients with RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC). Key results: at the 300 mg/day recommended Phase 2 dose, approximately 30% objective response rate was observed in patients with one prior line of chemotherapy — remarkably high for a cancer historically resistant to all targeted therapies. Across all patients regardless of prior therapy lines, approximately 90% disease control rate (tumor stabilization or reduction) was achieved, with median response duration of over 8 months in 1-prior-therapy patients. Safety profile was manageable; most common adverse events were rash, oral mucositis, nausea, and diarrhea. Lead investigator Dr. Brian Wolpin (Dana-Farber, Harvard Medical School) noted this represents the first targeted therapy to demonstrate meaningful clinical activity in KRAS-mutant pancreatic cancer — the dominant oncogenesis driver present in >90% of cases. These Phase 1/2 data complement the Phase 3 RASolute 302 topline results (13.2 vs. 6.7 months OS, HR 0.40) announced in April 2026. Full Phase 3 data will be presented at ASCO on May 31, 2026.