RASolute 302: Phase 3 trial in previously treated metastatic pancreatic adenocarcinoma
Design: a global, randomised, open-label, multicentre Phase 3 trial (NCT06625320) that enrolled 500 patients with metastatic pancreatic ductal adenocarcinoma who had progressed after one line of chemotherapy at 59 sites across North America, Europe and Asia. Patients were randomised 1:1 to daraxonrasib 300 mg orally once daily or one of four investigator's-choice standard intravenous chemotherapy regimens (most commonly gemcitabine plus nab-paclitaxel, and liposomal irinotecan plus 5-FU/leucovorin). The primary endpoints were overall survival (OS) and progression-free survival (PFS) in the RAS G12-mutant population and in the overall population.
Positive topline results were announced on April 13, 2026. The full data were presented by Prof. Brian M. Wolpin of the Dana-Farber Cancer Institute at the ASCO Annual Meeting Plenary Session (LBA5) on May 31, 2026, with simultaneous publication in the New England Journal of Medicine.
Efficacy (overall population, ITT)
| Endpoint | Daraxonrasib | Chemotherapy | Hazard ratio / p-value |
|---|---|---|---|
| Median overall survival | 13.2 months (95% CI 10.0–NE) | 6.7 months (95% CI 5.8–8.0) | HR 0.40 (95% CI 0.30–0.53), p < 0.0001 |
| Median progression-free survival | 7.2 months (95% CI 5.7–7.5) | 3.6 months (95% CI 2.9–4.2) | HR 0.49 (95% CI 0.38–0.64), p < 0.0001 |
| Objective response rate | 30% (95% CI 25–36) | 11% (95% CI 7–15) | p < 0.0001 |
Efficacy (RAS G12-mutant population)
| Endpoint | Daraxonrasib | Chemotherapy | Hazard ratio |
|---|---|---|---|
| Median overall survival | 13.2 months | 6.6 months | HR 0.40 |
| One-year survival rate | 53.3% | 18.7% | — |
| Median progression-free survival | 7.3 months | 3.5 months | HR 0.45 |
| 6-month progression-free rate | 58.7% | 31.7% | — |
Patient-reported outcomes (quality of life)
- Time to pain deterioration: 9.2 vs 3.8 months (HR 0.51, p < 0.0001)
- Time to deterioration in global health status / quality of life: 5.7 vs 2.6 months (HR 0.60, p = 0.0002)
Safety
- Grade ≥3 treatment-related adverse events: 43.6% (daraxonrasib) vs 57.5% (chemotherapy)
- Dose reductions due to adverse events: 36.1% vs 57.5%
- Discontinuation due to adverse events: 1.2% vs 11.2%
- The adverse events most often leading to dose reduction were rash (17.4%) and stomatitis (6.6%)
Phase 1/2 study: RMC-6236-001 (NCT05379985)
RMC-6236-001 is the first-in-human study of daraxonrasib, enrolling patients with a range of advanced RAS-mutant solid tumors to evaluate safety, pharmacokinetics, the recommended dose and preliminary efficacy. Data from the pancreatic cancer cohort, presented at ESMO, ASCO and other congresses during 2024–2025, showed progression-free and overall survival signals well above historical controls. They formed the basis of the FDA's Breakthrough Therapy Designation in June 2025 and directly supported the launch of RASolute 302.
Non-small cell lung cancer cohort (NEJM, September 2026)
| Measure | Result (160–220 mg dose group, n = 38) |
|---|---|
| Objective response rate | 42% |
| Median duration of response | 11.5 months |
| Median progression-free survival | 8.3 months |
| Median overall survival | 16 months |
| Grade ≥3 adverse events | 51% |
| Most common adverse events | Rash 90% (grade ≥3: 8%), diarrhoea 73%, nausea 62%, vomiting 54% |
| Dose modification / discontinuation | 71% / 10% |
These data supported the Phase 3 RASolve 301 trial (daraxonrasib vs docetaxel in previously treated RAS-mutant NSCLC), which dosed its first patient in May 2025.