FDA Accepts Daraxonrasib NDA for Previously Treated Metastatic Pancreatic Cancer

The U.S. Food and Drug Administration has accepted Revolution Medicines’ New Drug Application for daraxonrasib, an investigational oral RAS(ON) multi-selective inhibitor, for the treatment of adults with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). The application is supported by positive results from the global Phase 3 RASolute 302 trial, which demonstrated significant improvements in survival outcomes compared with standard chemotherapy.

If approved, daraxonrasib could become the first broad RAS-targeted therapy for previously treated metastatic PDAC, a disease with few effective treatment options and one of the lowest survival rates among solid tumors.

Daraxonrasib Targets the Central Driver of Pancreatic Cancer

RAS mutations are the dominant molecular drivers of pancreatic cancer, particularly PDAC. Unlike mutation-specific inhibitors, daraxonrasib is an oral, noncovalent RAS(ON) tri-complex inhibitor that suppresses signaling from both wild-type and multiple mutant RAS proteins by blocking their interaction with downstream effectors. This broad activity allows the therapy to target a wide range of RAS genotypes, including G12D, G12V, G12R, and tumors without an identified RAS mutation.

Metastatic PDAC remains one of the most aggressive malignancies. Most patients receive their diagnosis after the disease has already spread, and the five-year survival rate for metastatic disease is approximately 3%, highlighting the urgent need for more effective therapies.

Phase 3 RASolute 302 Trial Met Primary and Key Secondary Endpoints

The NDA is supported by the global Phase 3 RASolute 302 trial (NCT06625320), which enrolled approximately 500 patients with previously treated metastatic PDAC, including those with RAS G12-mutant tumors and patients without an identified RAS mutation. Participants received once-daily oral daraxonrasib 300 mg or investigator’s choice of standard cytotoxic chemotherapy.

The study met all primary and key secondary endpoints. Daraxonrasib nearly doubled median overall survival compared with chemotherapy, extending median OS to 13.2 months versus 6.6–6.7 months. Median progression-free survival also improved to 7.2 months versus 3.6 months. In addition, patients receiving daraxonrasib experienced delayed deterioration in cancer-related pain, overall global health status, and quality of life based on patient-reported outcomes.

The primary efficacy analyses focused on patients with tumors harboring RAS G12 mutations, while secondary analyses evaluated outcomes across the overall intent-to-treat population, including patients with and without identified RAS mutations. Additional secondary endpoints included objective response rate and duration of response.

Daraxonrasib also demonstrated a favorable safety profile. Grade 3 or higher treatment-related adverse events occurred in approximately 44% of patients receiving daraxonrasib compared with 58% of those treated with chemotherapy. Rash and stomatitis were the most common severe treatment-related adverse events. The Phase 3 findings were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine.

Regulatory Momentum Continues

The FDA selected the application for the Commissioner’s National Priority Voucher pilot program, which supports accelerated review of therapies addressing major public health priorities. Daraxonrasib has also received Breakthrough Therapy Designation and Orphan Drug Designation for previously treated metastatic PDAC.

Outside the United States, the European Medicines Agency (EMA) has initiated a phased review of daraxonrasib before submission of a full marketing authorization application. The therapy has also received orphan medicine designation in Europe and high-priority status under the EMA Cancer Medicines Pathfinder initiative.

Executive Perspective

Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines, said FDA acceptance marks an important milestone toward making daraxonrasib available to patients with previously treated metastatic pancreatic cancer. He noted that the Phase 3 RASolute 302 results demonstrated unprecedented clinical benefit and support the potential for daraxonrasib to establish a new treatment standard while advancing a broader class of RAS-targeted therapies.

Path Forward

Beyond pancreatic cancer, Revolution Medicines is evaluating daraxonrasib in a global Phase 3 development program that includes additional studies in PDAC and metastatic RAS-mutant non-small cell lung cancer (NSCLC). The FDA review represents the next major regulatory milestone and could introduce a targeted treatment option for a patient population that has seen limited therapeutic progress despite decades of research.

 Reference

Revolution Medicines’ New Drug Application for Daraxonrasib Accepted for Review by U.S. FDA for Previously Treated Metastatic Pancreatic Cancer | Revolution Medicines