Revolution Medicines reported high response activity for its second RAS inhibitor, zoldonrasib, in Phase 1/2 pancreatic ductal adenocarcinoma (PDAC) data focused on the KRAS G12D mutation. In RAS-G12D–mutated metastatic PDAC patients treated with zoldonrasib plus frontline mFOLFIRINOX, the overall response rate (ORR) reached 82%, compared with historical chemotherapy-only ORRs around 30% to 40%. The company also highlighted earlier ESMO GI plans that include additional combination readouts, including second-line data pairing zoldonrasib with daraxonrasib. Analysts cited the results as reinforcing Revolution’s opportunity to sustain leadership in PDAC amid expanding RAS-directed combinations. Revolution concurrently launched the Phase 3 RASolute 305 study testing zoldonrasib plus mFOLFIRINOX as a frontline regimen. If successful, the combination could expand options for patients with limited tolerability for more intensive regimens. The next major inflection for the program will come from the ongoing Phase 3 execution and how efficacy measures mature beyond early ORR signals.