Daraxonrasib, an oral targeted therapy developed by Revolution Medicines, nearly doubled median overall survival compared to standard chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma, delivering 13.2 months of median survival versus 6.7 months for chemotherapy and reducing the risk of death by 60%. The Phase 3 RASolute 302 trial results, published in The New England Journal of Medicine on May 31, 2026, and presented during the plenary session at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, represent a fundamental shift in how oncologists approach a cancer that kills nearly 53,000 Americans each year and carries a five-year survival rate of roughly 3% once it has spread.
Key Takeaways
- Daraxonrasib delivered median overall survival of 13.2 months versus 6.7 months for chemotherapy in patients with previously treated metastatic pancreatic cancer, a 60% reduction in the risk of death
- The Phase 3 RASolute 302 trial enrolled 500 patients with metastatic pancreatic ductal adenocarcinoma and met both co-primary endpoints of overall survival and progression-free survival
- The FDA has granted daraxonrasib Breakthrough Therapy designation and authorized an expanded access treatment protocol, making the drug available to eligible patients while regulatory review continues
- Revolution Medicines intends to submit approval applications under the FDA’s Commissioner’s National Priority Voucher pilot program for an expedited review process
- Researchers from NYU Langone Health, Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, and Johns Hopkins were among the trial investigators
Why Has Pancreatic Cancer Been So Difficult to Treat?
Pancreatic ductal adenocarcinoma accounts for more than 90% of pancreatic cancers and has resisted meaningful therapeutic advances for decades. The disease typically produces no symptoms until it has spread beyond the pancreas, meaning most patients are diagnosed at a metastatic stage where treatment options are limited. Chemotherapy regimens available for previously treated metastatic disease have offered modest survival benefits with significant toxicity, and patients who progress through first-line chemotherapy have historically faced a narrowing set of options with diminishing returns.
The biological reason for this treatment resistance centers on a family of proteins called RAS. Activating mutations in RAS drive the growth of more than 90% of pancreatic cancers, and for decades, these mutations were considered “undruggable” — present in nearly every tumor but resistant to targeted therapeutic intervention. The RAS protein’s smooth molecular surface offered few binding sites for traditional small-molecule drugs, and efforts to develop RAS-targeted therapies had failed repeatedly across multiple cancer types.
Daraxonrasib represents a different class of molecule: a RAS(ON) multi-selective inhibitor. Rather than attempting to lock onto a single mutant form of RAS, daraxonrasib is designed to suppress multiple oncogenic variants of active RAS proteins simultaneously. This broad coverage matters in pancreatic cancer because the disease harbors diverse RAS mutations — predominantly G12 variants, but also G13 and Q61 forms — and a therapy that addresses only one variant leaves others to continue driving tumor growth.
What Did the RASolute 302 Trial Show?
The RASolute 302 trial (ClinicalTrials.gov identifier NCT06625320) is a global, randomized, open-label Phase 3 study that enrolled 500 adults with metastatic pancreatic ductal adenocarcinoma who had received at least one prior line of treatment. Patients were randomized to receive either oral daraxonrasib or investigator’s choice chemotherapy.
The trial’s co-primary endpoints were overall survival and progression-free survival in patients with RAS G12 mutations, the most common mutational subtype. In that population, median overall survival reached 13.2 months with daraxonrasib compared to 6.6 months with chemotherapy — a hazard ratio of 0.40, translating to a 60% reduction in the risk of death. The result was statistically significant, with a p-value below 0.0001. Patients treated with daraxonrasib also survived more than twice as long before their disease progressed.
The overall study population, which included patients with G12, G13, Q61, and even unidentified RAS mutations, showed consistent benefit. The safety profile was manageable with no new signals identified beyond what earlier-phase trials had established. At the data cutoff, 42% of patients in the daraxonrasib arm remained on treatment, compared to 14% in the chemotherapy arm — a retention gap that reflects both the drug’s tolerability and its sustained clinical activity.
The lead investigator, Dr. Brian Wolpin of Dana-Farber Cancer Institute, received a standing ovation from the ASCO plenary audience when he presented the results — a reaction that the BMJ described as rare for a normally reserved scientific gathering.
Who Participated in the Research?
The RASolute 302 trial was a multi-institutional effort spanning cancer centers across the United States, Europe, and Japan. The New England Journal of Medicine publication lists investigators from Dana-Farber Cancer Institute in Boston, Memorial Sloan Kettering Cancer Center in New York, NYU Langone Health’s Perlmutter Cancer Center in New York, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Heidelberg University Hospital in Germany, and Kanagawa Cancer Center in Japan, among others.
Dr. Salman R. Punekar of NYU Langone Health served as a co-investigator on the trial, connecting the research directly to New York’s oncology infrastructure. Memorial Sloan Kettering’s Dr. Eileen O’Reilly, a recognized authority in pancreatic cancer, also contributed to the study. The breadth of participating institutions reflects both the global scale of the trial and the urgency with which the oncology community has pursued RAS-targeted therapies for a disease that has defied treatment advances for decades.
How Can Patients Access Daraxonrasib Now?
The FDA authorized an expanded access treatment protocol for daraxonrasib on May 1, 2026, allowing eligible patients with previously treated metastatic pancreatic cancer to receive the drug outside of clinical trials while regulatory review continues. Patients must have already gone through prior chemotherapy and meet specific clinical criteria, and the prescribing oncologist must request permission from Revolution Medicines before administering the drug.
Revolution Medicines announced its intention to submit a new drug application under the FDA’s Commissioner’s National Priority Voucher pilot program, which provides an expedited review pathway for therapies addressing urgent health priorities. Full FDA approval timing remains uncertain, but the company has indicated that a submission could occur later in 2026. The FDA had previously granted daraxonrasib both Breakthrough Therapy and Orphan Drug designations, reflecting the severity of the unmet medical need in pancreatic cancer.
Beyond the second-line setting, Revolution Medicines is advancing daraxonrasib into additional clinical trials. RASolute 303 is evaluating daraxonrasib as a monotherapy or in combination with standard chemotherapy as a first-line treatment for metastatic pancreatic cancer. RASolute 304 is studying adjuvant daraxonrasib in patients who have undergone surgical resection and completed chemotherapy — a setting where preventing recurrence could extend the drug’s impact to earlier-stage patients. Daraxonrasib is also being studied in other solid-tumor cancers driven by RAS mutations, with preliminary results described as promising by investigators involved in those trials.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Readers should consult qualified healthcare professionals regarding any medical conditions or treatment options.
FAQs
What is daraxonrasib? Daraxonrasib (RMC-6236) is an oral, once-daily RAS(ON) multi-selective inhibitor developed by Revolution Medicines. The drug is designed to suppress multiple oncogenic variants of active RAS proteins, which drive tumor growth in more than 90% of pancreatic cancers.
How much did daraxonrasib improve survival? In the Phase 3 RASolute 302 trial, patients treated with daraxonrasib lived a median of 13.2 months compared to 6.7 months for chemotherapy — a 60% reduction in the risk of death. Patients also experienced more than double the progression-free survival time.
Is daraxonrasib available to patients now? The FDA authorized an expanded access treatment protocol on May 1, 2026, allowing eligible patients with previously treated metastatic pancreatic cancer to receive daraxonrasib outside of clinical trials. Full FDA approval has not yet been granted but could come later in 2026.
Which institutions were involved in the clinical trial? Investigators from Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, NYU Langone Health’s Perlmutter Cancer Center, Johns Hopkins, Heidelberg University Hospital, and Kanagawa Cancer Center in Japan participated in the 500-patient Phase 3 RASolute 302 trial.
Why was pancreatic cancer previously so difficult to treat? Pancreatic cancer typically produces no symptoms until it has spread, limiting treatment options at diagnosis. The RAS mutations that drive more than 90% of cases were long considered “undruggable” because the RAS protein’s molecular surface offered few binding sites for traditional targeted drugs.
What other trials are underway for daraxonrasib? Revolution Medicines is running RASolute 303 (first-line treatment for metastatic pancreatic cancer) and RASolute 304 (adjuvant treatment after surgery). The drug is also being studied in other solid-tumor cancers driven by RAS mutations.
