Daraxonrasib Shows 58% ORR, 84% Six-Month PFS in First-Line Pancreatic Cancer
Updated Phase 1/2 data show daraxonrasib plus gemcitabine/nab-paclitaxel delivered a 58% ORR and 84% six-month PFS in 40 first-line metastatic pancreatic cancer patients with manageable Grade ≥3 TRAEs. In a 38-patient monotherapy cohort, daraxonrasib 300 mg daily produced a 47% ORR and 71% six-month PFS with no Grade 4-5 TRAEs.
1. Combination Cohort Data
Revolution Medicines revealed updated findings from the RMC-GI-102 trial evaluating daraxonrasib 200 mg daily plus gemcitabine and nab-paclitaxel in 40 patients with previously untreated metastatic PDAC. The combination achieved a confirmed objective response rate of 58% (95% CI: 41–73) and a Kaplan-Meier six-month PFS estimate of 84% (95% CI: 68–93).
2. Monotherapy Cohort Findings
In the RMC-6236-001 trial, 38 treatment-naïve metastatic PDAC patients received daraxonrasib 300 mg daily. The monotherapy cohort produced a 47% ORR (95% CI: 31–64), including one complete response, and a six-month PFS estimate of 71% (95% CI: 53–83), with median PFS and OS still immature.
3. Safety and Tolerability
Safety profiles in both cohorts aligned with known agent characteristics. Combination therapy saw Grade ≥3 TRAEs including anemia (33%), neutropenia (20%), and fatigue (18%), while monotherapy reported Grade ≥3 rash, diarrhea, and stomatitis in 38% of patients. No Grade 4 or 5 TRAEs were observed in the monotherapy group.
4. Ongoing Phase 3 Trials and Next Steps
These Phase 1/2 findings support the pivotal Phase 3 RASolute 303 trial in first-line metastatic PDAC. Daraxonrasib is also under evaluation in two additional PDAC Phase 3 studies and one in NSCLC to confirm survival benefits and safety in larger patient populations.