The Food and Drug Administration on Aug. 26 approved daraxonrasib (Rasonque, Revolution Medicines) for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. It is the first approved therapy that directly targets RAS in the most common form of pancreatic cancer.
Daraxonrasib is an oral, once-daily RAS(ON) multi-selective inhibitor. Unlike the mutation-specific KRAS inhibitors already approved in colorectal and lung cancer, which act on a variant rarely seen in pancreatic tumors, daraxonrasib suppresses signaling from both mutant and wild-type RAS in its active, GTP-bound state. Aberrant RAS signaling drives the large majority of pancreatic ductal adenocarcinoma (PDAC), with activating mutations present in more than 90% of tumors.
Roughly 90% to 95% of the approximately 67,000 pancreatic cancers diagnosed in the United States each year are adenocarcinomas, according to the National Cancer Institute figures cited by the agency. Although pancreatic cancer accounts for about 3.2% of cancer diagnoses, it contributes a disproportionate share of cancer deaths, a pattern the FDA attributed to late detection, aggressive biology, and limited treatment options.
Trial results behind the approval
The approval rests on RASolute 302 (NCT06625320), a global, randomized, open-label phase 3 trial that enrolled 500 patients with previously treated metastatic PDAC. Participants received either daraxonrasib 300 mg once daily (n = 248) or investigator's choice of one of four cytotoxic chemotherapy regimens (n = 252). The trial enrolled patients across a range of RAS variants as well as patients with no identified RAS mutation, with dual primary endpoints of overall survival (OS) and blinded independent central review–assessed progression-free survival (PFS) in the RAS G12 subgroup.
At the Feb. 10, 2026, data cutoff, median follow-up was 8.5 months. In the intention-to-treat population, median OS was 13.2 months with daraxonrasib versus 6.7 months with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53; P < .0001) — a 60% reduction in the risk of death. Median PFS was 7.2 months versus 3.6 months (HR, 0.49; 95% CI, 0.38-0.64; P < .0001), and objective response rates were 31.6% versus 11.2%. Results in the RAS G12 population were essentially superimposable, with a median OS of 13.2 months versus 6.6 months and an identical hazard ratio of 0.40.
Patient-reported outcomes favored the oral agent as well. Time to deterioration in cancer-related pain (HR, 0.51) and in global health status and quality of life (HR, 0.60) were both significantly delayed relative to chemotherapy.
Grade 3 or higher treatment-related adverse events occurred in 43.6% of patients on daraxonrasib versus 57.5% on chemotherapy, and the toxicity profiles differed in kind as well as degree. The most frequent grade 3 or higher events with daraxonrasib were rash (14%) and stomatitis (12%), compared with neutropenia (28%), anemia (16%), and thrombocytopenia (10%) on chemotherapy. Discontinuation for treatment-related toxicity occurred in 1.2% of the daraxonrasib arm versus 11.2% of the chemotherapy arm. One grade 5 treatment-related event, a case of pneumonitis, occurred in the daraxonrasib arm.
The FDA lists the most common adverse reactions as rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage.
An accelerated review
Daraxonrasib carried breakthrough therapy and orphan drug designations and received priority review. The application was also evaluated under the FDA's Commissioner's National Priority Voucher pilot program, which is intended to speed review of therapies addressing national public health priorities. The approval came 6.5 months ahead of the user fee goal date.
“This drug showed unprecedented results in an area of high unmet need,” said Angelo de Claro, MD, director of the FDA's Oncology Center of Excellence, in the agency's announcement.
The agency had already issued a "safe to proceed" letter in May allowing Revolution Medicines to open an expanded access protocol, giving eligible patients pre-approval access to the drug.
RASolute 302 results were presented in a plenary session at the 2026 American Society of Clinical Oncology Annual Meeting and published simultaneously in the New England Journal of Medicine. Principal investigator Brian M. Wolpin, MD, MPH, of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, said at the time that the findings would change how "scientists, clinicians, and patients think about treatment" for the disease.
Indication and ongoing trials
The approved indication covers two groups: adults who have received at least one prior systemic therapy, and adults who are not candidates for multiagent systemic therapy. It is therefore not limited to the second-line setting in which the pivotal trial was run.
Daraxonrasib is being studied earlier in the disease course. RASolute 303 (NCT07491445) is evaluating daraxonrasib alone or with gemcitabine and nab-paclitaxel against chemotherapy alone in the first-line metastatic setting, and RASolute 304 (NCT07252232) is testing adjuvant daraxonrasib versus observation after resection and perioperative chemotherapy. Additional trials are under way in non–small cell lung cancer and colorectal cancer.
Revolution Medicines has not yet disclosed pricing or a timeline for commercial availability.
Deeper dive
GI & Hepatology News has published a detailed research summary of the RASolute 302 trial, including the trial design, subgroup findings by RAS variant, patient-reported outcome measures, and the questions the trial leaves open about resistance and sequencing.