RevMed Reports RASONQUE Survival Benefit Across RAS Subgroups

Revolution Medicines reported exploratory analyses from the Phase 3 RASolute 302 trial showing that RASONQUE™ (daraxonrasib) improved overall survival (OS) compared with chemotherapy across evaluated tumor RAS subgroups in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). Presented as a late-breaking abstract at the European Society for Medical Oncology (ESMO) Congress 2026, the findings included patients whose tumors had no identified RAS mutation.

Overall Survival Results from RASolute 302

RASolute 302 was a randomized Phase 3 trial evaluating oral RASONQUE monotherapy against investigator-selected standard chemotherapy in previously treated metastatic PDAC. A total of 500 patients were randomized to receive RASONQUE 300 mg once daily (n=248) or chemotherapy (n=252).

In the previously reported primary analysis, based on a February 10, 2026, data cutoff and median follow-up of 8.5 months, median OS was 13.2 months with RASONQUE versus 6.7 months with chemotherapy (hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.30–0.53).

The new analyses examined whether the observed survival advantage was consistent across tumor RAS genotypes, chemotherapy regimens and prior-treatment settings. These were exploratory subgroup analyses rather than separate confirmatory efficacy assessments.

Survival Findings Across RAS Genotypes

The reported OS hazard ratios favored RASONQUE across all evaluated RAS subgroups:

The G12V subgroup had the lowest reported hazard ratio, at 0.32. However, subgroup hazard ratios should not be interpreted as proving greater efficacy in G12V tumors than in other genotypes without an appropriate comparative statistical analysis.

The result in tumors without an identified RAS mutation is also noteworthy because daraxonrasib is designed to inhibit active RAS signaling. Its HR of 0.43 suggests a favorable treatment effect, but the wide confidence interval indicates substantial uncertainty. The confidence intervals for G12R, Q61 and RAS-unidentified tumors included 1.0, so these analyses do not independently establish statistically significant survival benefits in those subgroups.

Findings Across Chemotherapy and Prior-Treatment Settings

RASONQUE also showed a favorable OS effect against three preselected standard chemotherapy comparators:

• Gemcitabine plus nab-paclitaxel: HR 0.45 (95% CI 0.32–0.65).
• Pooled modified FOLFIRINOX/FOLFOX: HR 0.46 (95% CI 0.23–0.95).
• Nanoliposomal irinotecan plus fluorouracil and leucovorin: HR 0.32 (95% CI 0.18–0.58).

The reported results suggest that the survival advantage was not confined to a single chemotherapy comparator.

The benefit was also observed across prior-treatment settings. Among patients whose metastatic disease was diagnosed less than six months after their last dose of neoadjuvant or adjuvant therapy, the HR was 0.36 (95% CI 0.17–0.75). Among patients who had received one prior line of therapy for metastatic disease, the HR was 0.43 (95% CI 0.32–0.58).

Together, these findings broaden the evidence supporting RASONQUE across clinically relevant patient groups, although the exploratory nature of the analyses remains an important limitation.

Regulatory Status and Safety Considerations

RASONQUE is an oral, RAS(ON) multi-selective, noncovalent tri-complex inhibitor. The US Food and Drug Administration has approved it for adults with metastatic PDAC who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy.

On October 15, 2026, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion recommending marketing authorization. This recommendation is distinct from final European Commission authorization. The company has stated that RASONQUE remains investigational outside the United States.

Important safety considerations include dermatologic and soft-tissue toxicity, stomatitis, diarrhea, gastrointestinal perforation, interstitial lung disease or pneumonitis, and embryo-fetal toxicity. In clinical trials involving patients with pancreatic adenocarcinoma, dermatologic toxicity occurred in 86% of patients, stomatitis in 57% and diarrhea in 63%. The 86% figure refers to dermatologic toxicity overall, not rash alone.

What the Findings Mean

The ESMO 2026 analyses extend the reported survival results from RASolute 302 by showing a consistent direction of treatment effect across evaluated RAS genotypes, chemotherapy comparators and prior-treatment settings. The finding in tumors without an identified RAS mutation is particularly notable, but its wide confidence interval warrants caution. Further interpretation should distinguish the overall trial’s survival results from exploratory subgroup estimates that do not independently establish benefit in every patient group.

 References

Revolution Medicines Presents Overall Survival Data for RASONQUE™ (daraxonrasib) Across Subgroups in Previously Treated Metastatic Pancreatic Cancer at ESMO 2026, ClinicalTrials.gov ID NCT06625320

Phase 3 Study of Daraxonrasib (RMC-6236) in Patients with Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (RASolute 302), ClinicalTrials.gov ID NCT06625320