Daraxonrasib Doubles Overall Survival in Previously Treated Metastatic Pancreatic Cancer

Revolution Medicines reported positive topline findings from the global Phase 3 RASolute 302 trial, showing that the oral RAS(ON) inhibitor significantly improved both progression-free survival and overall survival compared with investigator’s choice of intravenous cytotoxic chemotherapy. The study met all primary and key secondary endpoints.

In the intent-to-treat population, median overall survival reached 13.2 months with daraxonrasib, versus 6.7 months with chemotherapy, corresponding to a hazard ratio of 0.40, p < 0.0001. According to the company, the first interim analysis is also considered final for both progression-free survival and overall survival endpoints. Daraxonrasib was generally well tolerated, with a manageable safety profile and no new safety signals.

The result is particularly notable in pancreatic cancer, where more than 90% of tumors are driven by RAS alterations and where progress after first-line treatment has been incremental. Daraxonrasib is a multi-selective, non-covalent inhibitor of RAS(ON) proteins, developed to target a broad spectrum of oncogenic RAS drivers rather than a single variant.

“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” said Dr. Brian M. Wolpin, professor of medicine at Harvard Medical School, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial. “The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy. I believe that this new approach is a very important advance for the field that I expect will be practice-changing for physicians and improve the care for patients with previously treated metastatic pancreatic cancer.”

RASolute 302, NCT06625320, is an ongoing global randomized registrational trial comparing once-daily daraxonrasib 300 mg with standard chemotherapy in patients with previously treated metastatic PDAC. The primary endpoints focus on progression-free survival and overall survival in tumors harboring RAS G12 mutations, while secondary analyses assess outcomes across the full enrolled population, including patients with other RAS variants and those without an identified RAS mutation. Additional endpoints include objective response, duration of response, and patient-reported quality of life.

“In this pivotal trial, daraxonrasib as a targeted medicine delivered a dramatic improvement in overall survival in patients with previously treated metastatic pancreatic cancer compared to standard of care chemotherapy, consistent with earlier findings. These results represent a potentially transformative advance for patients and underscore daraxonrasib’s potential to redefine the treatment landscape. We are moving with urgency toward global regulatory submissions and remain committed to rapidly advancing this therapy for patients with a broad range of RAS-addicted cancers. We look forward to sharing detailed results with the scientific and clinical communities,” commented Dr. Mark A. Goldsmith, chief executive officer and chairman of Revolution Medicines.

The company said it plans to include the data in a future New Drug Application to the FDA, under the agency’s Commissioner’s National Priority Voucher program, and to present detailed results at the 2026 ASCO Annual Meeting. Daraxonrasib has not yet been approved in the United States or Europe.

Dr. Goldsmith added, “We believe these results firmly validate our pioneering approach to targeting common RAS-addicted cancers through RAS(ON) inhibition, exemplified today by four clinical-stage, investigational drugs with differentiated profiles. This class of inhibitors reflects more than 15 years of investment in groundbreaking scientific research, including creative work from Warp Drive Bio, acquired by Revolution Medicines in 2018, which established the initial technology foundation we have developed into a robust innovation engine for delivering and sustaining our compelling pipeline.”