First RAS inhibitor doubles pancreatic-cancer survival in Phase 3 trial

June 3, 2026 4 min read Multiple sources

On Sunday at ASCO, oncology's largest annual meeting, the plenary audience interrupted Brian Wolpin's slides with a standing ovation. The data on screen showed daraxonrasib, a daily pill from Revolution Medicines, cutting the risk of death by 60% in patients whose metastatic pancreatic cancer had stopped responding to chemotherapy. For a disease that has shrugged off almost every targeted therapy ever tested, the number is unfamiliar territory.

The trial

RASolute 302 randomized 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC, the most common form of pancreatic cancer) to 300 mg of daraxonrasib once a day (248 patients) or their oncologist's pick of four standard chemotherapy regimens (252 patients). The results were published in The New England Journal of Medicine the same afternoon Wolpin took the stage.

Dr. Eileen O'Reilly, gastrointestinal oncologist at Memorial Sloan Kettering and co-investigator on the daraxonrasib trial — Source: Memorial Sloan Kettering Cancer Center

Median overall survival (the point at which half the patients in a group have died) ran 13.2 months on the pill versus 6.7 months on chemotherapy, a hazard ratio of 0.40, meaning patients on daraxonrasib were dying at 40% the rate of the chemo arm. Progression-free survival ran 7.2 months versus 3.6 months. In the largest mutation subgroup, objective tumor shrinkage hit 33.2% with the pill versus 11.8% with chemo. P-values were below 0.0001 on every primary endpoint.

The drug's target is the reason all of this matters. Daraxonrasib blocks proteins encoded by the RAS gene, which is mutated in over 90% of pancreatic adenocarcinomas. RAS was famously labeled "undruggable" for forty years — its surface is smooth, with no obvious pocket for a small molecule to grab. Revolution Medicines designed daraxonrasib to bind the active form of RAS across multiple variants, not just one.

Why it matters

PDAC is the worst major cancer to be diagnosed with. Five-year survival in the U.S. sits around 12%, and most patients are already metastatic at diagnosis. Until Sunday, no second-line therapy (treatment given after first-round chemo has stopped working) had pushed median survival past a year in a Phase 3 trial. Doubling it changes what counts as a control arm for the next generation of trials.

The safety profile is not free. About 86% of patients on daraxonrasib developed a rash (14% severe), and 54% developed stomatitis (painful mouth sores; 12% severe). Grade 3 or worse drug-related side effects hit 43.6% of the pill arm. The countervailing number: only about 1% of daraxonrasib patients discontinued for side effects, versus about 11% on chemotherapy. Patients tolerated the toxicities; they did not tolerate the chemo.

Helene Rubin, a patient in the daraxonrasib pancreatic cancer trial, photographed outdoors with American flags — Source: Memorial Sloan Kettering Cancer Center

The strongest counter is that "investigator's choice of chemotherapy" is a low bar in second-line PDAC. Most options have median survival in the single-digit months and were never compared head-to-head against each other. A 0.40 hazard ratio is still a 0.40 hazard ratio, but the comparator is part of why it looks so large. Daraxonrasib has not yet been tested against the strongest combination chemo regimens in first-line patients.

Revolution Medicines shares jumped about 20% overnight on the data. The FDA already issued a safe-to-proceed letter on May 1 for an expanded-access program, and the company is preparing a rolling NDA submission.

What to watch

The first-line readout. RASolute 301 is testing daraxonrasib plus chemo against chemo alone in newly diagnosed metastatic PDAC patients. If it lands anywhere near the second-line numbers, the standard of care for the deadliest major cancer in the U.S. will shift within two years. Watch ASCO 2027 in Chicago.

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