Daraxonrasib (RMC-6236) RAS(ON) tri-complex inhibitor delivers 37% ORR in previously treated RAS-mutant NSCLC

Daraxonrasib (RMC-6236) is an oral, multiselective RAS(ON) tri-complex inhibitor that binds active, GTP-bound mutant and wild-type RAS isoforms; it was evaluated in the Phase 1–2 RMC-6236-001 study (NCT05379985) in previously treated advanced/metastatic RAS-mutant NSCLC. At the July 21, 2025 data cutoff, 136 patients receiving ≤300 mg once daily were evaluable, with investigator-assessed ORR increasing by dose: 31% at ≤120 mg, 34% at 160–220 mg, and 37% at 300 mg. That response rate is similar to KRAS G12C inhibitors such as sotorasib (~37%) and adagrasib (~43%), but daraxonrasib potentially extends targeted therapy across multiple RAS mutations rather than G12C alone. Grade ≥3 adverse events occurred in 54% regardless of attribution, while grade ≥3 treatment-related adverse events occurred in 30%; four grade 5 events occurred, none considered treatment-related.