On April 13, 2026, Revolution Medicines announced positive topline results from the global Phase 3 RASolute 302 clinical trial evaluating daraxonrasib in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines, said:
“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 are deeply grateful to the patients, families, investigators, and study teams whose participation made the RASolute 302 trial possible, and we look forward to sharing detailed results with the scientific and clinical communities.”
The company stated that it intends to submit these data to global regulatory authorities, including the U.S. Food and Drug Administration, and present the results at the 2026 American Society of Clinical Oncology Annual Meeting.
Study Design and Methods
RASolute 302 (NCT06625320) is an ongoing, global, randomized Phase 3 registrational trial designed to evaluate daraxonrasib as monotherapy in patients with previously treated metastatic PDAC.
Patients were randomized to receive either daraxonrasib at a dose of 300 mg orally once daily or investigator’s choice of standard-of-care cytotoxic chemotherapy. The trial enrolled patients with tumors harboring a range of RAS variants, including RAS G12 mutations such as G12D, G12V, and G12R, as well as patients without an identified RAS mutation.
The primary endpoints were progression-free survival and overall survival in patients with tumors harboring RAS G12 mutations. Secondary endpoints included progression-free survival and overall survival in the overall intent-to-treat population, as well as objective response rate, duration of response, and patient-reported quality of life.
You can also read about RASolute 303 Trial on OncoDaily.
Results
Revolution Medicines reported that daraxonrasib demonstrated statistically significant improvements in both progression-free survival (PFS) and overall survival (OS) compared with standard-of-care cytotoxic chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma.
In the overall (intent-to-treat) population, median overall survival was 13.2 months with daraxonrasib compared with 6.7 months with chemotherapy, corresponding to a hazard ratio of 0.40 (p < 0.0001). Based on the first interim analysis, all progression-free survival and overall survival endpoint results are considered final.
Daraxonrasib was administered orally once daily and was generally well tolerated, with a manageable safety profile and no new safety signals reported.
“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, ” said Dr. Goldsmith.
What is Daraxonrasib and How Does it Work?
Daraxonrasib is an investigational, oral RAS(ON) multi-selective, non-covalent inhibitor that is not approved by any regulatory authority, including in the United States or Europe. According to Revolution Medicines, daraxonrasib is designed to target cancers driven by a broad range of common RAS mutations, including pancreatic ductal adenocarcinoma, non-small cell lung cancer, and colorectal cancer.
It works by suppressing RAS signaling through inhibition of the interaction between both wild-type and mutant RAS(ON) proteins and their downstream effectors.
Clinical Context
According to the American Cancer Society, pancreatic cancer represents about 3% of all cancers in the United States but accounts for approximately 8% of cancer-related deaths.
In 2026, an estimated 67,530 people (35,190 men and 32,340 women) will be diagnosed with pancreatic cancer, while about 52,740 patients (27,230 men and 25,510 women) are expected to die from the disease. The average lifetime risk is approximately 1 in 56 for men and 1 in 60 for women.
Clinically, pancreatic cancer is often diagnosed at an advanced stage, with around 80% of patients presenting with metastatic disease. Outcomes remain poor, with a five-year survival rate of approximately 3% in this setting.
At the biological level, pancreatic cancer is driven predominantly by RAS signaling, with more than 90% of tumors harboring RAS mutations.
Regulatory Outlook
Daraxonrasib has received Breakthrough Therapy Designation and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of previously treated metastatic PDAC harboring G12 mutations.
It has also been selected for the FDA Commissioner’s National Priority Voucher program.
The drug is currently being evaluated in multiple Phase 3 trials across RAS-driven cancers, including pancreatic cancer, non-small cell lung cancer, and colorectal cancer.
Investigator Perspective
Brian M. Wolpin, M.D., M.P.H., 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, said:
“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life. 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.”
Conclusion
The Phase 3 RASolute 302 trial showed that daraxonrasib improved progression-free survival and overall survival compared with standard-of-care chemotherapy in patients with previously treated metastatic PDAC.
The full article is available in Revolution Medicines.