Daraxonrasib NEJM Publication (May 2026): Revolution Medicines' RAS(ON) Inhibitor Hit 35% ORR + 13.1-Month OS in RAS G12-Mutated Pancreatic Cancer Phase 1/2
The New England Journal of Medicine published Revolution Medicines' daraxonrasib (RMC-6236) Phase 1/2 data in previously treated advanced RAS-mutated pancreatic adenocarcinoma in May 2026. In the subgroup of 26 patients with G12 mutations treated at the 300 mg dose, objective response rate hit 35% with median progression-free survival 8.5 months and median overall survival 13.1 months — outcomes meaningfully better than the historical 5-month median OS in second-line PDAC. The mechanism is unusual: daraxonrasib is an oral small molecule that acts as a molecular glue, recruiting the peptidyl-prolyl isomerase cyclophilin A to form a tri-complex with active GTP-bound mutant RAS, blocking effector binding and downstream signaling. The drug targets KRAS, HRAS, and NRAS in the on-state — a mechanistically distinct approach from Chugai's LUNA18 cyclic peptide RAS inhibitor. FDA granted Expanded Access. The cyclophilin A-mediated mechanism puts peptidyl-prolyl chemistry at the center of a major oncology readout.