FDA Allows Expanded Access to Daraxonrasib for PDAC

The FDA has authorized Revolution Medicines to launch an expanded access treatment protocol (EAP) for its investigational RAS inhibitor daraxonrasib for the treatment of patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).¹

Previously reported topline results from the phase 3 RASolute 302 trial (NCT06625320) showed that daraxonrasib reduced the risk of death by 60% vs chemotherapy in this setting.² This impressive result in a difficult-to-treat population resulted in a rapid 2-day turnaround from Revolution Medicines requesting and receiving approval for expanded access (April 28 to April 30).

“Granting the request [2] days after receiving the expanded access application reflects the FDA’s strong commitment to facilitate early access to therapies for serious and life-threatening conditions, including pancreatic cancer,” FDA Commissioner Marty Makary, MD, MPH, stated in a news release.¹ “Having taken care of many patients with metastatic cancer, I am hopeful that today’s action will improve the lives of patients suffering from this disease.”

Phase 3 RASolute 302 Trial of Daraxonrasib

Survival results in the RASolute 302 trial showed that the median OS in the intent-to-treat population was 13.2 months with daraxonrasib vs 6.7 months for chemotherapy, translating to a 60% reduction in the risk of death (HR, 0.40; P <.0001). The trial also met its primary end points of progression-free survival (PFS) and OS in patients with tumors harboring RAS G12 mutations.²

Regarding safety, daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals.

Overall, RASolute 302 is an ongoing, global, randomized, controlled registrational trial enrolling patients with previously treated metastatic PDAC. Patients were randomized to daraxonrasib 300 mg orally once daily or investigator's choice of standard-of-care cytotoxic chemotherapy. Enrollment included patients across a broad range of RAS variants: including G12D, G12V, and G12R mutations, as well as patients with RAS wild-type tumors.³

The primary end points were PFS and OS in patients with RAS G12 mutation–positive tumors, as assessed by blinded independent central review. Secondary end points included PFS and OS in the full intent-to-treat population, objective response rate, duration of response, and patient-reported quality of life.²

The FDA previously granted daraxonrasib breakthrough therapy designation and orphan drug designation for previously treated metastatic PDAC harboring G12 mutations. Daraxonrasib has also been selected for the FDA Commissioner's National Priority Voucher pilot program. Revolution Medicines intends to submit a new drug application to the FDA under this pathway and to submit data to other global regulatory authorities.

The full primary and final analysis from RASolute 302 are being presented by Brian Wolpin, MD, MPH in a plenary session at the 2026 ASCO Annual Meeting.

“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” 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, stated in a recent new release announcing the OS data.²

“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,” added Wolpin.

REFERENCES

1. U.S. Food and Drug Administration. FDA permits expanded access for investigational pancreatic cancer drug. FDA News Release. Published April 30, 2026. Accessed May 1, 2026. https://tinyurl.com/58rz3ue7

2. Daraxonrasib demonstrates unprecedented overall survival benefit in pivotal phase 3 RASolute 302 clinical trial in patients with metastatic pancreatic cancer. News release. Revolution Medicines. April 13, 2026. Accessed May 1, 2026. https://tinyurl.com/y6z9rxmy

3. Phase 3 study of daraxonrasib (RMC-6236) in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) (RASolute 302). ClinicalTrials.gov. Updated December 12, 2025. Accessed May 1, 2026. https://clinicaltrials.gov/study/NCT06625320