Revolution Medicines (Nasdaq: RVMD) released the full Phase III dataset at this year's American Society of Clinical Oncology (ASCO) meeting showing that daraxonrasib, an oral RAS(ON) multi-selective inhibitor, cut the risk of death by 60% compared to standard chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). The results confirm the earlier release of topline figures, and represent one of the largest survival improvements ever reported in a Phase III trial for previously treated metastatic PDAC and could establish the first broadly applicable targeted therapy for the majority of patients with RAS-driven disease.
The RASolute 302 trial is a global, randomized Phase III study that enrolled 500 patients with previously treated metastatic PDAC, including those with RAS G12 mutations and a smaller group without an identified tumor RAS mutation. Patients were randomized to 300 mg oral daraxonrasib once daily or investigator's choice of four cytotoxic chemotherapy regimens. At a February 2026 data cutoff, median OS in the RAS G12 population reached 13.2 months with daraxonrasib versus 6.6 months with chemotherapy (HR 0.40; 95% CI: 0.30–0.54; p < 0.0001); results in the intent-to-treat population were nearly identical. Median PFS doubled as well, at 7.3 versus 3.5 months in the RAS G12 group (HR 0.45; p < 0.0001), and objective response rates were 33.2% versus 11.8%. The safety profile favored daraxonrasib on most measures: Grade 3 or higher treatment-related adverse events occurred in 43.6% of patients on daraxonrasib versus 57.5% on chemotherapy, and treatment discontinuation due to adverse events was strikingly low at 1.2% versus 11.2%. The most common high-grade events with daraxonrasib were rash and stomatitis; one fatal pneumonitis was reported. Results were simultaneously published in The New England Journal of Medicine as well as featuring in the ASCO 2026 Annual Meeting plenary session.
Daraxonrasib works by blocking the interaction between active RAS(ON) proteins — both wild-type and mutant forms — and their downstream effectors, a mechanistic approach distinct from the allele-specific KRAS(OFF) inhibitors that have reshaped lung cancer treatment. In the broader PDAC landscape, current second-line treatment largely relies on chemotherapy regimens such as Onivyde-based combinations and fluoropyrimidine-containing protocols, which typically deliver median overall survival measured in months rather than years. Biomarker-selected approvals for Merck's Keytruda (pembrolizumab) and AstraZeneca's Lynparza (olaparib) reach perhaps 10% of patients collectively. Cross-trial comparisons are limited, but no prior Phase III trial in any line of PDAC therapy has reported a median OS exceeding one year. Revolution Medicines intends to file a New Drug Application with the FDA under the Commissioner's National Priority Voucher program; an expanded access protocol is already open.
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