FDA Approves First-in-Class RAS Inhibitor for Metastatic Pancreatic Cancer

The US Food and Drug Administration (FDA) has approved daraxonrasib (Rasonque), a first-in-class oral RAS inhibitor, for adults with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or are not candidates for multiagent systemic therapy. The approval arrived 6.5 months ahead of the agency's user fee deadline.

Daraxonrasib is a once-daily tablet that targets multiple forms of RAS, a protein that drives tumor growth in more than 90% of patients with pancreatic adenocarcinoma, the form of cancer that arises from cells lining the pancreatic ducts. It is the first RAS(ON) multi-selective inhibitor to reach approval, designed to address a broader range of RAS mutations, including G12, G13, and Q61 variants, than earlier KRAS-directed agents.

“Today’s approval provides a critical new option for patients facing an extraordinarily difficult and historically hard-to-treat cancer. It is our fundamental duty to deliver more cures and meaningful treatments to patients as quickly as possible,” Acting FDA Commissioner Kyle Diamantas, J.D., said in a statement.

A Cancer That Outpaces Its Treatment Options

Pancreatic adenocarcinoma accounts for approximately 90% to 95% of the 67,000 new pancreatic cancer cases diagnosed in the US each year, according to the National Cancer Institute. Although the disease represents roughly 3.2% of all cancer diagnoses, it accounts for a disproportionately high share of cancer deaths, a burden attributed to late detection, an aggressive disease course, and historically limited treatment options.

RASolute 302 Trial Data: A 60% Reduction in Risk of Death

The approval was based on RASolute 302 (NCT06625320), a global, randomized, open-label, phase 3 trial that enrolled 500 adults with metastatic pancreatic adenocarcinoma previously treated with a single line of 5-fluorouracil-based or gemcitabine-based therapy. Patients were randomized 1:1 to daraxonrasib or investigator's choice of standard-of-care chemotherapy.

In the intent-to-treat population, daraxonrasib produced a median overall survival of 13.2 months, compared with 6.7 months among patients who received chemotherapy, a reduction in the risk of death of approximately 60% (HR, 0.40; P < .0001). The trial's primary endpoints, progression-free survival and overall survival, were assessed specifically in patients whose tumors carried RAS G12 mutations, while secondary endpoints captured progression-free survival, overall survival, objective response rate, duration of response, and quality of life across the full enrolled population, including patients with RAS wild-type tumors. Findings from the trial were published in the New England Journal of Medicine.

“This drug showed unprecedented results in an area of high unmet need,” Angelo de Claro, MD, director of the FDA’s Oncology Center of Excellence, said in a statement. “The approval was granted 6.5 months before the user fee deadline, demonstrating the FDA’s commitment to accelerating the approval of new cancer treatments for patients with serious and life-threatening conditions.”

A Review Accelerated by 4 Regulatory Pathways

Daraxonrasib received Breakthrough Therapy and Orphan Drug designations from the FDA, along with Priority Review for this indication. The application was also reviewed under the Commissioner’s National Priority Voucher pilot program, which is intended to accelerate review of therapies addressing national public health priorities.

In May 2026, the FDA issued a "safe to proceed" letter permitting the drug's sponsor to initiate an expanded access treatment protocol, allowing patient access ahead of approval under applicable FDA regulations.

Rash and Diarrhea Among the Most Common Adverse Events

The most common side effects associated with daraxonrasib include rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Across RASolute 302, daraxonrasib was described as generally well tolerated, with no new safety signals identified beyond this known profile.