RASolute 302 — Daraxonrasib (RMC-6236) Versus Investigator's Choice of Chemotherapy in Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (RASolute 302)

Phase 3 · 2026 · Pancreatic Cancer

Design

Global, open-label, randomized phase 3 trial. Patients were randomized 1:1 to oral daraxonrasib 300 mg once daily or investigator's choice of standard-of-care cytotoxic chemotherapy. Dual primary endpoints were OS and PFS by BICR in the RAS G12-mutant population; key secondary endpoints assessed OS, PFS, and ORR in the overall (intent-to-treat) population.

Population

Previously treated (second-line) metastatic pancreatic ductal adenocarcinoma with ECOG PS 0–1, enrolling tumors with a range of RAS variants as well as RAS wild-type disease.

Primary Endpoint

overall survival (OS) and progression-free survival (PFS) by BICR in the RAS G12-mutant population

Key Result

Daraxonrasib met all primary and key secondary endpoints. In the overall population, median OS was 13.2 vs 6.7 months (HR 0.40, 95% CI 0.30–0.53; P<0.001) and median PFS 7.2 vs 3.6 months (HR 0.49; P<0.001), with ORR 31.6% vs 11.2%. Benefit was consistent across cohorts, including tumors with common KRAS G12 mutations (median OS 13.2 vs 6.6 months, HR 0.40; median PFS 7.3 vs 3.5 months, HR 0.45; ORR 33.2% vs 11.8%) as well as other RAS variant alterations. Daraxonrasib was better tolerated than chemotherapy: the most frequent adverse events were rash, oral inflammation/swelling (stomatitis),…

Guideline Impact

Second-line metastatic pancreatic ductal adenocarcinoma