A Phase 3 trial reported that daraxonrasib—an oral RAS(ON) multiselective inhibitor—significantly improved overall survival and progression-free survival versus investigator’s choice chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma. The study targeted the RAS G12 population in a prespecified subgroup analysis and also included an overall population with RAS variants. In the RAS G12 subgroup, median overall survival was 13.2 months with daraxonrasib versus 6.6 months with chemotherapy, with a hazard ratio of 0.40. Median progression-free survival was 7.3 months versus 3.5 months, and similar hazard ratios were reported in the overall population. Safety signals showed adverse events in all treated patients in the daraxonrasib arm, with grade 3 or higher events occurring in 61.8% compared with 69.6% in chemotherapy. Treatment discontinuation due to treatment-related adverse events occurred in 1.2% versus 11.2%. For metastatic pancreatic cancer, where outcomes remain poor, these results raise the probability of a meaningful next-line option and will likely drive follow-up regulatory planning and competitive positioning among RAS-pathway efforts.