Revolution Medicines' Daraxonrasib Cuts Death Risk 60% in Pancreatic Cancer; EMA Starts Rolling Review

Revolution Medicines' experimental oral pancreatic cancer drug daraxonrasib met all primary and key secondary endpoints in the pivotal Phase 3 RASolute 302 trial, reducing the risk of death by 60% (hazard ratio 0.40) compared with chemotherapy in patients with metastatic pancreatic cancer. Patients treated with the once-daily pill achieved a median overall survival of 13.2 months versus 6.7 months for those receiving standard chemotherapy, a benefit the company's CEO described as 'dramatic, practice-changing outcomes.' The trial enrolled an all-comers second-line pancreatic ductal adenocarcinoma population, and both progression-free survival and overall survival results were declared final. The data were presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in the New England Journal of Medicine.

Daraxonrasib is an oral, multi-selective, RAS(ON) non-covalent tri-complex inhibitor. In the RASolute 302 trial, treated patients with metastatic pancreatic ductal adenocarcinoma, with or without a RAS mutation, also showed delayed cancer-related pain and improved overall quality of life. The company intends to include the data in a future New Drug Application submission to the U.S. Food and Drug Administration and to other global regulatory authorities. The company plans to seek FDA approval using a National Priority Voucher that expedites review, and the NDA is advancing under a rolling submission. Daraxonrasib previously received Breakthrough Therapy and Orphan Drug designations from the FDA.

The European Medicines Agency has begun a rolling review of daraxonrasib for patients with metastatic pancreatic cancer, based on results from the late-stage study. Patients whose disease progresses after earlier treatment have limited therapeutic options and a poor prognosis, with life expectancy of about six months, the EMA said. Daraxonrasib was designated a high-priority medicine under the agency's Cancer Medicines Pathfinder program. Under the rolling review process, the EMA's Committee for Medicinal Products for Human Use will evaluate quality, safety and efficacy data as they become available, ahead of a formal marketing application. In May, the FDA authorized early access before regulatory approval to the pill for patients with previously treated pancreatic cancer.

Separately, Revolution Medicines presented proof-of-concept data from two Phase 1/2 trials of its oral RAS(ON) G12D-selective inhibitor zoldonrasib at ESMO GI. In first-line metastatic RAS G12D pancreatic ductal adenocarcinoma, zoldonrasib was tested with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel; as of a February 8, 2026 cutoff, 81 patients had been enrolled across both arms. Grade 3 or higher treatment-related adverse events occurred in 61% of patients in the FOLFIRINOX arm and 80% in the gemcitabine/nab-paclitaxel arm, with no treatment-related deaths reported, and dose intensity remained high at 86% and 90%, respectively. In a second study, 60 heavily pretreated patients with metastatic pancreatic cancer received zoldonrasib in combination with daraxonrasib; grade 3 or higher adverse events occurred in 35% of patients, with rash, anemia, and stomatitis/mucositis among the most common severe toxicities. In second-line patients, the objective response rate was 50% with a disease control rate of 97%, and median progression-free survival reached 9.6 months. In third-line and beyond patients, response rates remained 47%, with median progression-free survival of 7.6 months and median overall survival of 10.5 months.

Revolution Medicines has begun treating patients in the Phase 3 RASolute 305 study evaluating zoldonrasib plus chemotherapy in first-line metastatic RAS G12D PDAC. Participants receive either zoldonrasib plus investigator-selected standard-of-care chemotherapy or placebo plus chemotherapy, with chemotherapy options including modified FOLFIRINOX or gemcitabine and nab-paclitaxel. The co-primary endpoints are progression-free survival and overall survival. More than 90% of PDAC tumors harbor RAS mutations, with RAS G12D present in about 40% of patients, and the five-year survival rate for metastatic PDAC is around 3%. Beyond RASolute 305, the company is developing daraxonrasib in the ongoing Phase 3 RASolute 303 study as a monotherapy and in combination with chemotherapy for first-line metastatic PDAC, and is advancing three additional registrational Phase 3 studies in PDAC covering adjuvant resectable disease, first-line metastatic monotherapy and combination settings, and a RAS(ON) inhibitor doublet pairing daraxonrasib with zoldonrasib. The $2.2 billion raised in gross proceeds this year supports a platform capable of running six or more concurrent registrational trials. The Phase 3 NSCLC program in RAS G12D is fully enrolled in its Phase 2 expansion cohort, with a registrational trial imminent.