FDA approves daraxonrasib, the first targeted therapy for metastatic pancreatic cancer

The U.S. Food and Drug Administration approved Rasonque (daraxonrasib) on 26 August 2026, the first targeted therapy ever approved for metastatic pancreatic cancer. The sponsor is Revolution Medicines, and the application, NDA 220910, was cleared under priority review according to the Drugs@FDA record. The approved indication is the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.

Daraxonrasib is a once-daily oral RAS(ON) multiselective tri-complex inhibitor. It binds the active, GTP-bound state of mutant and wild-type RAS. Oncogenic RAS mutations are present in more than 90 per cent of pancreatic ductal adenocarcinomas, and RAS was regarded as undruggable for four decades after its discovery as a human oncogene.

The registrational trial, RASolute 302, is registered on ClinicalTrials.gov as NCT06625320. It was a phase 3, international, open-label, randomised trial in 500 patients with previously treated metastatic pancreatic ductal adenocarcinoma. Of those, 248 were assigned to daraxonrasib and 252 to investigator's-choice chemotherapy, and 91.8 per cent carried RAS G12 mutations.

Median overall survival in the RAS G12 population was 13.2 months with daraxonrasib against 6.6 months with chemotherapy, and in the overall population 13.2 against 6.7 months. In both populations the hazard ratio was 0.40, with P less than 0.001. Median survival was therefore roughly double that achieved with chemotherapy.

Median progression-free survival in the RAS G12 population was 7.3 against 3.5 months, and in the overall population 7.2 against 3.6 months, with hazard ratios of 0.45 and 0.49 respectively and P less than 0.001 for both.

Tolerability favoured the targeted drug. Grade 3 or higher adverse events occurred in 61.8 per cent of patients taking daraxonrasib against 69.6 per cent on chemotherapy, and treatment-related discontinuations in 1.2 per cent against 11.2 per cent. The most common adverse events are rash, diarrhoea, stomatitis, nausea, fatigue, vomiting, abdominal pain, oedema, decreased appetite and haemorrhage.

Acting FDA Commissioner Kyle Diamantas said: “Today's approval provides a critical new option for patients facing an extraordinarily difficult cancer.” Dr Angelo de Claro, Director of the FDA's Oncology Center of Excellence, said: “This drug showed unprecedented results in an area of high unmet need.”

The review drew on four expedited mechanisms: Breakthrough Therapy designation, Orphan Drug designation, Priority Review and the Commissioner's National Priority Voucher pilot programme. The FDA approved the drug 6.5 months ahead of the user fee goal date.

The agency set the approval against the burden of the disease. Pancreatic cancer accounts for roughly 67,000 new cases a year in the United States and 3.2 per cent of all cancer diagnoses. Adenocarcinoma makes up 90 to 95 per cent of those cases, and mortality is disproportionately high.

The RASolute 302 results were published in the New England Journal of Medicine, volume 395, issue 4, pages 325 to 337, with the digital object identifier 10.1056/NEJMoa2605555 and the PubMed identifier 42223072. The first author is Eileen M. O'Reilly of Memorial Sloan Kettering Cancer Center and the senior author is Brian M. Wolpin, Director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute. Co-investigators worked in the United States, Italy, France, Germany and Japan.

Revolution Medicines is testing daraxonrasib in first-line pancreatic cancer and in RAS-mutant lung and colorectal cancer. The approval also opens the question of whether pan-RAS inhibition can be combined with chemotherapy or immunotherapy without prohibitive toxicity.