OncoMatch/Clinical Trials/Daraxonrasib

Daraxonrasib (RMC-6236) Clinical Trials

Daraxonrasib (RMC-6236) is an oral RAS(ON) multi-selective inhibitor — a pan-RAS agent that targets the active, GTP-bound state of multiple RAS variants rather than a single mutation such as KRAS G12C. The FDA approved it as RASONQUE on August 26, 2026 for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy; the approved indication is defined by disease and prior treatment, and does not require a RAS mutation test. Approval rested on RASolute 302, which randomized 500 patients 1:1 against physician’s choice of chemotherapy: median overall survival 13.2 months versus 6.7 (hazard ratio 0.40, 95% CI 0.30–0.53), progression-free survival 7.2 versus 3.6 months, and overall response 30% versus 11%. The recommended dose is 300 mg orally once daily until disease progression or unacceptable toxicity, and labeled warnings include dermatologic and soft-tissue toxicity, stomatitis and other oral disorders, diarrhea, gastrointestinal perforation, interstitial lung disease/pneumonitis, and embryo-fetal toxicity. Daraxonrasib continues to be studied beyond that indication — in RAS-mutant non-small cell lung and colorectal cancer, in earlier lines of pancreatic cancer, and combined with the G12D-selective agent zoldonrasib (RMC-9805) — and those trials, unlike the approved indication, generally do require a documented RAS mutation.