GFH375 + cetuximab + oxaliplatin + leucovorin + fluorouracil

GFH375 + cetuximab + oxaliplatin + leucovorin + fluorouracil is an investigational combination regimen being evaluated for the treatment of KRAS G12D-mutant metastatic colorectal cancer (mCRC). The regimen combines GFH375 (VS-7375), an orally active, potent, and highly selective small-molecule KRAS G12D inhibitor that targets both the active (GTP-bound, ON) and inactive (GDP-bound, OFF) states of the mutated protein, with cetuximab, an anti-EGFR monoclonal antibody, and the standard mFOLFOX6 chemotherapy backbone (comprising oxaliplatin, leucovorin, and fluorouracil). Mechanistically, direct KRAS G12D inhibition by GFH375 blocks downstream MAPK pathway signaling, while the addition of cetuximab prevents EGFR-mediated feedback reactivation, a common resistance mechanism to KRAS inhibitors in colorectal cancer. The cytotoxic chemotherapy components (oxaliplatin and fluorouracil, with leucovorin as a biomodulator) provide synergistic tumor-cell killing. This combination is being evaluated in clinical trials, such as the Phase 2 TARGET-D 203 study, as a first-line treatment option for patients with KRAS G12D-mutated mCRC.

Other names

GFH375 + cetuximab + FOLFOXGFH375 + cetuximab + FOLFOX6GFH375 + cetuximab + mFOLFOX6GFH375 + cetuximab + oxaliplatin + folinic acid + 5-fluorouracilGFH375 + cetuximab + oxaliplatin + folinic acid + fluorouracilGFH375 + cetuximab + oxaliplatin + leucovorin + 5-fluorouracilVS-7375 + cetuximab + FOLFOXVS-7375 + cetuximab + FOLFOX6VS-7375 + cetuximab + mFOLFOX6VS-7375 + cetuximab + oxaliplatin + folinic acid + 5-fluorouracilVS-7375 + cetuximab + oxaliplatin + folinic acid + fluorouracilVS-7375 + cetuximab + oxaliplatin + leucovorin + 5-fluorouracilVS-7375 + cetuximab + oxaliplatin + leucovorin + fluorouracil