Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Additional subgroup analyses from the ph3 RASolute 302 study

RASolute 302

Patient / Population Intervention / Exposure Comparison Outcome

In previously treated metastatic pancreatic adenocarcinoma, daraxonrasib showed a directionally consistent overall survival benefit across tumour RAS mutation subgroups compared with standard chemotherapy.

N

—patients

Design

Phase 3 trial randomising patients with previously treated metastatic pancreatic adenocarcinoma 1:1 to oral daraxonrasib or investigator's choice of standard chemotherapy (GnP, mFOLFIRINOX, Nal-IRI+5-FU/LV or FOLFOX) (NCT06625320).

Endpoint

Dual primary endpoints of overall survival and progression-free survival in the RAS G12 mutant population. Key secondary endpoints were overall survival and progression-free survival in the overall population.

ResultIn the RAS G12 mutant population, OS HR 0.40 and PFS HR 0.45 with daraxonrasib vs chemotherapy. In the overall population, median OS 13.2 vs 6.7 months (HR 0.40) and median PFS 7.2 vs 3.6 months (HR 0.49). OS HR by tumour RAS mutation status: G12D 0.49 (95% CI 0.33-0.74), G12V 0.32 (95% CI 0.19-0.54), G12R 0.61 (95% CI 0.29-1.30), RAS Q61 0.37 (95% CI 0.09-1.44) and no RAS mutation identified 0.43 (95% CI 0.09-1.98). OS HRs across preselected chemotherapy subgroups ranged from 0.32 to 0.46.

Wainberg ZA, Wolpin BM, Hendifar AE, et al. Presented at ESMO Congress 2026, abstract LBA82, 23 October. Not yet published.

Discussion & critique

This analysis shows OS hazard ratios favouring daraxonrasib in every reported RAS mutation subgroup and in every preselected chemotherapy subgroup, which supports the primary analysis. The subgroups are small: G12R, RAS Q61 and the group with no RAS mutation identified each have wide confidence intervals that cross 1, so in those groups the benefit is only directionally consistent and not established. Median follow-up was only 8.5 months. The abstract does not report blinding, gives no P values, and gives the chemotherapy subgroup HRs without confidence intervals or patient numbers. Results by the setting of prior treatment and the safety data for these subgroups are not reported in the abstract.