zoldonrasib + cetuximab + leucovorin + fluorouracil + irinotecan

The combination of zoldonrasib, cetuximab, leucovorin, fluorouracil, and irinotecan is an investigational multi-drug oncology regimen being evaluated for the treatment of KRAS G12D-mutant gastrointestinal cancers, particularly metastatic colorectal cancer (mCRC). Zoldonrasib (RMC-9805) is an oral, covalent, tri-complex RAS(ON) G12D-selective inhibitor that acts as a molecular glue, forming a ternary complex with cyclophilin A and active GTP-bound KRAS G12D to block downstream MAPK signaling. Cetuximab is an anti-EGFR monoclonal antibody that prevents feedback reactivation of the MAPK pathway. Leucovorin, fluorouracil, and irinotecan constitute the standard FOLFIRI cytotoxic chemotherapy regimen, which induces DNA damage and apoptosis by inhibiting thymidylate synthase and topoisomerase I. This combination is being evaluated in clinical trials, including the Phase 1/2 platform study NCT06445062 (Subprotocol G) and the Phase 3 RASonate 312 trial, to overcome resistance and improve outcomes in patients with KRAS G12D-mutated colorectal cancer.

Other names

RMC-9805 + cetuximab + FOLFIRIRMC-9805 + cetuximab + FOLFIRI regimenRMC-9805 + cetuximab + leucovorin + fluorouracil + irinotecanzoldonrasib + cetuximab + FOLFIRIzoldonrasib + cetuximab + FOLFIRI regimenzoldonrasib + cetuximab + leucovorin + fluorouracil + irinotecan