The US FDA has approved Rasonque (daraxonrasib), Revolution Medicines' first-in-class RAS(ON) multi-selective inhibitor, for adults with metastatic pancreatic adenocarcinoma following prior systemic therapy or who are not candidates for multiagent systemic therapy. The biomarker-unrestricted approval gives Revolution Medicines its first commercial product and brings RAS-directed therapy to a broad pancreatic cancer population, where oncogenic RAS alterations are present in approximately 90–95% of tumors.
The FDA granted the approval 6.5 months ahead of the product's user fee deadline under the Commissioner's National Priority Voucher pilot program. Rasonque had also received Breakthrough Therapy, Orphan Drug, and Priority Review designations. The drug is administered orally once daily, and the approved indication does not require testing for a specific RAS mutation.
Approval was supported by the randomized, open-label Phase III RASolute 302 trial, which enrolled 500 adults with previously treated metastatic PDAC. Daraxonrasib nearly doubled median overall survival to 13.2 months from 6.7 months with investigator's choice of standard chemotherapy, corresponding to a 60% reduction in the risk of death reported at ASCO 2026. The most common adverse events included rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.
Daraxonrasib is designed to inhibit multiple oncogenic RAS variants by recruiting cyclophilin A to form a tri-complex with RAS, blocking downstream signaling. Its activity spans common PDAC-associated mutations including KRAS G12D, G12V, and G12R, distinguishing it from earlier mutation-specific KRAS inhibitors such as sotorasib and adagrasib, which target KRAS G12C — a variant found in only approximately 1–2% of pancreatic cancers.