Revolution Medicines’ second-generation RAS inhibitor zoldonrasib posted Phase 1/2 response data that suggest high activity in RAS-G12D-mutated metastatic pancreatic ductal adenocarcinoma (PDAC). In reported results to be presented at the ESMO Gastrointestinal Cancers Congress, the drug combined with frontline mFOLFIRINOX drove an 82% overall response rate (ORR) in patients with the RAS-G12D mutation. The data set compares against reported historical chemotherapy ORR estimates of roughly 30% to 40% in the same treatment setting. Revolution also reported manageable safety, with toxicities described as consistent with known chemotherapy effects. The company is already moving zoldonrasib into a new Phase 3 program, RASolute 305, testing zoldonrasib plus mFOLFIRINOX as first-line therapy in PDAC. Revolution plans ESMO GI presentations that also include second-line combination data pairing zoldonrasib with daraxonrasib, which showed a 50% ORR. Wall Street and competitors will watch the Phase 3 readout timetable and whether the mechanism-specific enrichment translates into survival endpoints at scale.