An international Phase 3 trial reported that daraxonrasib (an oral RAS(ON) multiselective tri-complex inhibitor) improved overall survival and progression-free survival versus investigator’s-choice chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma. Results were strongest in the prespecified RAS G12 mutation subgroup. The study randomized 500 patients, with 91.8% carrying RAS G12 mutations, to daraxonrasib or chemotherapy. Median overall survival was 13.2 months in the daraxonrasib arm versus 6.6 months with chemotherapy in the RAS G12 population, alongside significant improvements in progression-free survival. Safety showed grade 3+ adverse events in both arms, with fewer treatment discontinuations attributed to therapy in the daraxonrasib group versus chemotherapy. The data extend targeted RAS inhibition into an aggressive setting where durable outcomes remain difficult, and may shape the next regulatory and trial strategy for RAS-driven pancreatic cancer.