RevMed’s Daraxonrasib Cuts Death Risk by 60% in PDAC

Revolution Medicines reported positive Phase 3 results showing that daraxonrasib reduced the risk of death by 60% while significantly improving progression-free survival and quality of life in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).

Results from the global RASolute 302 trial (NCT06625320) were presented during a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine.

Scientific and Clinical Context

PDAC remains one of the deadliest cancers, with limited treatment options after first-line treatment failure. Because aberrant RAS signaling drives most pancreatic tumors, daraxonrasib was developed as an oral RAS(ON) multi-selective inhibitor that targets active RAS signaling across a broad range of RAS variants.

Trial Design and Patient Population

The randomized Phase 3 trial enrolled 500 patients with metastatic PDAC who had progressed after first-line therapy. Patients received once-daily daraxonrasib (n=248) or investigator’s choice of chemotherapy (n=252). The study evaluated outcomes in both patients with RAS G12-mutant tumors and the overall intent-to-treat (ITT) population.

Survival and Efficacy Outcomes

The trial met its primary endpoint of overall survival and key secondary endpoint of progression-free survival.

Daraxonrasib reduced the risk of death by 60% versus chemotherapy and extended median overall survival to 13.2 months compared with 6.6 months in the RAS G12-mutant population. Similar benefits were observed in the ITT population.

Progression-free survival also improved substantially, reaching 7.3 months versus 3.5 months in the RAS G12-mutant subgroup and 7.2 months versus 3.6 months in the overall population.

Objective response rates reached 33.2% in RAS G12-mutant patients and 31.6% in the ITT population, compared with 11.2% for chemotherapy.

Quality of Life and Safety

Beyond tumor control, daraxonrasib significantly delayed deterioration in cancer-related pain, overall health status, and quality of life compared with chemotherapy.

The therapy demonstrated a manageable safety profile. Grade 3 or higher treatment-related adverse events occurred in 43.6% of patients receiving daraxonrasib versus 57.5% with chemotherapy. Treatment-related serious adverse events occurred in 10.8% and 18.7% of patients, respectively, while treatment discontinuations were markedly lower with daraxonrasib (1.2% vs. 11.2%). Rash and stomatitis were the most common severe treatment-related adverse events.

Clinical Significance and Regulatory Pathway

Chief Executive Officer Mark Goldsmith said the findings validate the company’s strategy of targeting RAS-driven cancers and support the broader potential of RAS(ON) inhibition. Principal investigator Brian Wolpin of Dana-Farber Cancer Institute described the results as a major advance for metastatic pancreatic cancer and said they support a new treatment paradigm in the disease.

Revolution Medicines plans to submit the data to global regulatory authorities, including the U.S. Food and Drug Administration, as part of a New Drug Application supported by a Commissioner’s National Priority Voucher. The FDA has also authorized an expanded access program for eligible patients.

If approved, daraxonrasib could become the first RAS(ON) inhibitor to establish a new standard of care for previously treated metastatic pancreatic cancer and mark a major advance for RAS-targeted therapy across multiple tumor types.

Reference

Revolution Medicines Announces ASCO Plenary Presentation Highlighting Unprecedented Results from Pivotal Phase 3 RASolute 302 Clinical Trial of Daraxonrasib in Previously Treated Metastatic Pancreatic Cancer | Revolution Medicines