Medicine

Phase 3 trial: daraxonrasib raised median survival to 13.2 vs 6.6 months on chemo in RAS-mutant pancreatic cancer

In RASolute 302, a Phase 3 trial of 500 patients with treated RAS-mutant pancreatic cancer, daraxonrasib raised median survival to 13.2 vs 6.6 months on chemo, a 60% lower death risk.

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The evidence

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Evidence certainty

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The five checks

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Source tier

Peer-reviewed · New England Journal of Medicine

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Study type

Phase 3

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Sample size (n)

500

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Effect size (absolute)

median overall survival 13.2 vs 6.6 months in the RAS G12 population (6.6-month absolute difference); hazard ratio 0.40.

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Disease burden

RAS mutations drive more than 90% of pancreatic ductal adenocarcinomas (NEJM, this paper). Pancreatic cancer has among the lowest survival of major cancers. The American Cancer Society Cancer Statistics 2026 report puts all-type pancreatic cancer five-year relative survival at 13% in the United States, with an estimated 67,530 new US cases and 52,740 deaths in 2026, making it the third-leading cause of US cancer death. For ductal adenocarcinoma specifically, which is the disease studied here, the ACS five-year figure is about 8%; the all-type 13% is lifted by slower-growing neuroendocrine tumors.

Primary source: New England Journal of Medicine.View primary source Registration NCT06625320 Read the Lumen Standard

What this does and doesn’t mean

Open-label trial: patients and investigators knew the assignment, which can bias subjective endpoints like response and quality of life. Overall survival, a death-counted endpoint, is robust to this. The 13.2 vs 6.6 month figure is the primary endpoint in the RAS G12 subpopulation. In the overall population the chemotherapy arm was 6.7 months, with the same hazard ratio of 0.40. Toxicity is real: adverse events occurred in every patient who received daraxonrasib, and 61.8% had grade 3 or higher events. Only confirmed RAS-mutant patients were enrolled, so the result does not generalize to the small minority of pancreatic cancers without a RAS driver. Not FDA approved. The FDA granted expanded access, which lets some patients receive an investigational drug outside a trial and is not the same as approval. Industry-funded: the trial was paid for by Revolution Medicines, the drug's maker.

Peer-reviewedBy Nathan Stanley Martanegara25 June 20262 min read

Phase 3 trial: daraxonrasib raised median survival to 13.2 vs 6.6 months on chemo in RAS-mutant pancreatic cancer

Why it matters: Pancreatic ductal adenocarcinoma is one of the deadliest common cancers, and once it has progressed on first-line treatment, the options are few and survival is measured in months. RAS, the gene mutated in more than 90% of these tumors, was long considered undruggable. This is the first Phase 3 trial of an oral RAS(ON) multi-selective inhibitor to report a survival benefit in this setting. The absolute gain in median survival was 6.6 months, and the relative reduction in the risk of death was 60%. The drug is not approved, the trial was open-label, and the side effect burden is high, so the result is a meaningful signal that still needs the qualifications below.

Why RAS was called undruggable?
Most pancreatic cancers are driven by a mutation in RAS, a protein that sits at the center of the signals telling a cell to grow. The New England Journal of Medicine paper notes that oncogenic RAS mutations are present in more than 90% of cases. For decades RAS resisted direct drugs: its surface offered no good pocket for a molecule to grab, and it cycles between an active and inactive state too quickly to catch. Daraxonrasib is described by the authors as an oral RAS(ON) multi-selective, tri-complex inhibitor that targets the active, guanosine triphosphate-bound state of both mutant and normal RAS.

The trial and the numbers, in absolute terms
RASolute 302 was an international, open-label, randomized Phase 3 trial. A total of 500 patients with previously treated metastatic pancreatic cancer were assigned to daraxonrasib (248 patients) or chemotherapy of the investigator's choice (252 patients); 91.8% had RAS G12 mutations. In the RAS G12 population, median overall survival was 13.2 months with daraxonrasib and 6.6 months with chemotherapy. In the overall population it was 13.2 months versus 6.7 months. The hazard ratio for death was 0.40 in both populations, which corresponds to a 60% relative reduction in the risk of death (p less than 0.001). Median progression-free survival in the RAS G12 population was 7.3 months versus 3.5 months (hazard ratio 0.45). The objective response rate was 33.2% with daraxonrasib versus 11.8% with chemotherapy.
The side effect profile The benefit came with a high adverse-event burden. Adverse events after the start of treatment were reported in all patients in the daraxonrasib group and in 97.7% of the chemotherapy group. Grade 3 or higher adverse events occurred in 61.8% of the daraxonrasib group and 69.6% of the chemotherapy group. Treatment-related adverse events leading to discontinuation were less common with daraxonrasib than chemotherapy, at 1.2% versus 11.2%. The most common adverse events with daraxonrasib were rash and diarrhea.
Expanded access is not approval The FDA has granted expanded access to daraxonrasib. Expanded access, sometimes called compassionate use, allows patients with serious conditions to receive an investigational therapy outside a clinical trial when no comparable approved option exists. It is a pre-approval pathway, not a determination that the drug is safe and effective, which is what full approval would represent. As of this trial's publication the drug is not approved.

What's next?First-line data for daraxonrasib in pancreatic cancer were also presented at ASCO 2026 as a conference abstract (LB337). That material is earlier-stage and conference-tier rather than a peer-reviewed Phase 3 publication, and it is noted here only to flag that it exists, not as a verified result.

Source: New England Journal of Medicine · Nathan Stanley Martanegara · 25 June 2026