Redefining the treatment of RAS-mutant cancers
Daraxonrasib (RMC-6236)

Daraxonrasib (development code RMC-6236, U.S. brand name RASONQUE) is an oral RAS(ON) multi-selective inhibitor developed by Revolution Medicines. By forming a cyclophilin A–drug–RAS tri-complex, it blocks active mutant and wild-type RAS proteins from signalling downstream, thereby inhibiting tumor growth. It was approved by the U.S. FDA on August 26, 2026 for metastatic pancreatic adenocarcinoma.

Sotorasib and adagrasib bind covalently to the cysteine of the KRAS G12C mutant and lock RAS in its inactive (OFF) state, so they only work in patients with a G12C mutation. Daraxonrasib directly inhibits RAS in its active (ON) state and does not depend on a specific mutant residue, so it is active against G12D, G12V, G12R, G12C, G13 and Q61 mutations as well as wild-type RAS — a far larger population, and particularly relevant in pancreatic cancer, where G12D, G12V and G12R predominate.

The FDA-approved indication is adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multi-agent systemic therapy. The indication is not restricted by RAS mutation status. Other indications (first-line pancreatic cancer, adjuvant therapy, non-small cell lung cancer and others) remain in Phase 3 clinical trials.

The FDA-approved indication does not require a specific RAS mutation status; in RASolute 302 both the RAS G12-mutant population and the overall population benefited. That said, more than 90% of pancreatic adenocarcinomas carry a KRAS mutation, and molecular testing helps characterise the tumor and guide subsequent treatment choices. Follow your physician's advice and the current prescribing information.