Drug intelligence / Profile preview

MK-1084 + cetuximab + oxaliplatin + leucovorin + 5-fluorouracil

Development stage
Phase 3
Lead developer
Merck
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

This combination is an investigational regimen for advanced colorectal cancer with KRAS G12C mutation. It comprises MK-1084, an oral, selective, covalent KRAS G12C inhibitor; cetuximab, an anti-EGFR monoclonal antibody; and the mFOLFOX6 chemotherapy backbone (oxaliplatin, leucovorin, 5-fluorouracil). MK-1084 inhibits mutant KRAS G12C protein, blocking downstream oncogenic signaling. Cetuximab targets the epidermal growth factor receptor, preventing ligand binding and subsequent activation. Oxaliplatin is a platinum-based cytotoxic agent causing DNA crosslinking. Leucovorin enhances 5-fluorouracil efficacy by stabilizing binding to thymidylate synthase. 5-fluorouracil is a pyrimidine analog and antimetabolite, inhibiting DNA synthesis. This quadruplet is being developed for patients with advanced or metastatic colorectal cancer (CRC), especially those with the KRAS G12C mutation, who have received limited or no prior systemic therapy[2][3].

Brand names
None for full combination
Other names
mFOLFOX6 plus MK-1084 and cetuximabmFOLFOX-6 plus MK-1084 and cetuximabmFOLFOX 6 plus MK-1084 and cetuximab
02

Targets

DNAEGFR (Epidermal growth factor receptor)KRASG12C (Kirsten rat sarcoma viral oncogene homolog G12C)TS (Thymidylate synthase)

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