Daraxonrasib (RMC-6236) RAS(ON) multiselective inhibitor delivers 35% ORR in 2L RAS G12 PDAC

Daraxonrasib (RMC-6236) is an oral RAS(ON) multiselective inhibitor that binds GTP-bound mutant and wild-type RAS, evaluated in the Phase 1/2 RMC-6236-001 study (NCT05379985) in previously treated RAS-mutated PDAC. Across 168 treated PDAC patients (≤300mg), treatment-related AEs occurred in 96% with Grade 3+ TRAEs in 30% (notable ≥10%: rash, diarrhea, nausea, stomatitis/mucositis, vomiting, fatigue). In the 2L subgroup with RAS G12 mutations treated at 300mg (n=26), ORR was 35% (95% CI, 17–56) with median DoR 8.2 months, mPFS 8.5 months, and mOS 13.1 months; across RAS G12/G13/Q61 at 300mg (n=38), ORR was 29% with DoR 8.2 months, mPFS 8.1 months, and mOS 15.6 months—well above historical 2L NAPOLI-1 liposomal irinotecan + 5-FU/LV benchmarks (mOS ~6.1 months; mPFS ~3.1 months; ORR typically in the single digits).