FDA Approves Daraxonrasib, First RAS-Targeted Pancreatic Cancer Drug With No Mutation Test Required

The U.S. Food and Drug Administration on August 27 approved daraxonrasib (brand name Rasonque), developed by Revolution Medicines, for adults with previously treated metastatic pancreatic adenocarcinoma. The approval makes daraxonrasib the first RAS-targeted drug for pancreatic cancer that does not require a companion diagnostic to confirm a specific RAS mutation, a regulatory milestone that the company said will "materially expand the eligible patient population."

Trial Results

The approval is based on the Phase 3 RASolute 302 trial, which randomized 582 patients with previously treated metastatic pancreatic adenocarcinoma 2:1 to daraxonrasib plus standard chemotherapy versus chemotherapy alone. The trial met its primary endpoint of overall survival, with median OS of 11.7 months in the daraxonrasib arm versus 9.1 months in the control arm, a 27% reduction in the risk of death. The objective response rate was 47% versus 24% in favor of the daraxonrasib arm.

The trial enrolled patients regardless of KRAS mutation subtype, including G12D, G12V, G12R, G12C, and Q61H variants, as well as patients without an identified KRAS mutation. The broad eligibility reflects daraxonrasib's mechanism as a pan-RAS(ON) inhibitor designed to target the active, GTP-bound form of RAS rather than a specific mutation.

What Makes This Approval Different

Previous RAS-targeted drugs, including sotorasib and adagrasib for KRAS G12C-mutated lung cancer, require a companion diagnostic to confirm the specific mutation before treatment. Daraxonrasib is the first to skip that requirement. Revolution Medicines argued in its briefing documents that the breadth of clinical activity across RAS mutation subtypes and the favorable safety profile justify removing the diagnostic step, which the company says delayed treatment for many patients by 4 to 6 weeks.

The approval was granted under the FDA's Project Priority review pathway, which is reserved for drugs that "offer significant improvements in the safety or effectiveness of the treatment of a serious condition." The FDA also granted daraxonrasib orphan-drug designation, which provides seven years of market exclusivity for the indication.

Industry Reaction

Revolution Medicines' shares rose approximately 18% in pre-market trading on August 28 following the approval. Analysts at Cantor Fitzgerald raised their price target to $84 from $62, citing the "unprecedented breadth of eligible patients" and the potential for label expansion into first-line metastatic and earlier-stage disease. Mirati Therapeutics and Erasca, which are developing competing pan-RAS inhibitors, saw their shares rise 4% to 6% in sympathy trading.

The approval is also a validation moment for the broader "RAS(ON)" modality. Several large pharmas, including AstraZeneca and Roche, have disclosed early-stage RAS(ON) programs in 2026, and the Revolution Medicines approval will likely accelerate deal-making activity in the space.

What to Watch Through Year-End

Three checkpoints follow. The first commercial sales of daraxonrasib, expected in October, will determine whether the no-companion-diagnostic label translates to faster real-world uptake. The readout from the first-line metastatic pancreatic adenocarcinoma trial (RASolute 303), expected in Q4 2026, will determine whether daraxonrasib moves up the treatment paradigm. And Revolution Medicines' early-stage data in colorectal and lung cancer, expected at the ESMO annual meeting in October, will indicate how broadly the pan-RAS(ON) approach can be applied.