Daraxonrasib doubles survival in patients with metastatic pancreatic cancer

Abstract

Compared with chemotherapy, treatment with daraxonrasib more than doubled overall survival (OS) and progression-free survival (PFS) for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC) according to results from RASolute 302 presented at the 2026 annual meeting of the American Society of Clinical Oncology and published simultaneously in The New England Journal of Medicine.¹

“About 90% of pancreatic cancers harbor mutations in KRAS,” explains Vaia Florou, MD, an associate professor in the Division of Oncology at Huntsman Cancer Institute at the University of Utah in Salt Lake City. Previously approved KRAS inhibitors sotorasib and adagrasib both target KRAS G12C mutations, which are uncommon in pancreatic cancer. “Daraxonrasib is a pan-RAS inhibitor, covering multiple different RAS mutations.”

The RASolute 302 trial enrolled 500 patients with previously treated mPDAC and randomly assigned them to daraxonrasib or the investigator’s choice of chemotherapy. The trial had dual primary endpoints of OS and PFS in the subpopulation of patients with RAS G12 mutations, who composed 91.8% of the study patients.

Daraxonrasib yielded a 60% reduction in the risk for progression or death in patients with RAS G12 mutations and in the entire study population (hazard ratio [HR], 0.40; p < .001). The median OS was 13.2 months for patients with RAS G12 mutations who were assigned to daraxonrasib and 6.6 months for patients who were assigned to chemotherapy. For the entire study population, the median OS was 13.2 months with daraxonrasib and 3.6 months with chemotherapy.

Similarly, PFS was significantly improved in both populations. In patients with RAS G12 mutations, the median PFS was 7.3 months with daraxonrasib and 3.5 months with chemotherapy (HR, 0.45; p < .001), and in the entire population, the median PFS was 7.2 months with daraxonrasib and 3.6 months with chemotherapy (HR, 0.49; p < .001).

Treatment was discontinued because of adverse events in 1.2% of patients assigned to daraxonrasib and in 11.2% of patients assigned to chemotherapy.

“This is a landmark study in a way that is going to be a paradigm shift in how we treat this disease,” Dr Florou says.

Ongoing trials are evaluating daraxonrasib in newly diagnosed mPDAC (RASolute 303) and in the localized setting (RASolute 304). Additionally, other RAS inhibitors are being investigated in clinical trials targeting the G12D and G12V mutations, which are the most common RAS G12 variants in PDAC.

Before the publication of these results, the US Food and Drug Administration (FDA) announced that it has permitted expanded access to daraxonrasib for patients with previously treated mPDAC.²

“This is a great avenue for access to this drug or any effective drug before it goes to market,” says Dr Florou. “The caveat is that expanded access is not logistically easy to do. It may still take weeks or months to gain access, but that is still better than waiting on final [FDA] approval.”

Daraxonrasib’s manufacturer has announced that it intends to submit a new drug application under the FDA Commissioner’s National Priority Voucher pilot program.²