Dr Wainberg on RASolute 302: Daraxonrasib Across KRAS Variants

Zev A. Wainberg, MD, MSc, shares an update from the phase 3 RASolute 302 trial (LBA82) presented at the 2026 European Society for Medical Oncology (ESMO) Congress. The update focuses on how daraxonrasib (Rasonque) performed against chemotherapy across specific RAS mutation subgroups.

Wainberg is professor of medicine at UCLA and co-director of the UCLA GI Oncology Program. He explains that the ESMO update examined outcomes across individual RAS genotype subgroups. The analysis included the predominant KRAS mutations, G12D and G12V, as well as the less common KRAS G12R and RAS Q61 subgroups, along with patients for whom no RAS mutation was identified. Examining outcomes by individual RAS genotype provides a more detailed view of whether the benefit of daraxonrasib was consistent across the molecular subgroups represented in the trial.

According to Wainberg, overall survival (OS) favored daraxonrasib over chemotherapy across the RAS subgroups evaluated. The OS hazard ratios pointed in favor of daraxonrasib for G12D, G12V, G12R, RAS Q61, and tumors with no identified RAS mutation. The consistency in the direction of effect across these groups is a central takeaway from the update. However, the smaller subgroups had wide confidence intervals, making those estimates less precise and limiting the conclusions that can be drawn from individual subgroup results.

Wainberg also notes that the results are not entirely uniform across RAS genotypes. He points to differences in objective response rate (ORR) and progression-free survival (PFS), indicating that the magnitude of benefit may vary according to the specific RAS alteration. For example, the response and PFS findings were numerically less favorable in the G12R subgroup than in the larger G12D and G12V groups. He emphasizes that some subgroup findings are difficult to interpret statistically because of the small numbers of patients in certain categories.

Overall, Wainberg summarizes that daraxonrasib favored OS across the RAS genotype subgroups analyzed in RASolute 302. In this interview, he discusses the OS, ORR, and PFS findings by genotype and the statistical challenges of evaluating small molecular subgroups in a phase 3 study.