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avutometinib + defactinib + cetuximab
- Development stage
- Phase 2
- Lead developer
- Verastem Oncology
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Avutometinib + defactinib + cetuximab is an investigational combination therapy being evaluated in a Phase 2 clinical trial (NCT06072781) led by the M.D. Anderson Cancer Center for patients with unresectable, anti-EGFR-refractory advanced colorectal cancer. Avutometinib (VS-6766) is a first-in-class small molecule dual RAF/MEK inhibitor that functions as a RAF/MEK clamp by inducing inactive complexes between MEK and ARAF, BRAF, or CRAF. Defactinib is a small molecule inhibitor of Focal Adhesion Kinase (FAK), which is often upregulated as a resistance mechanism to MAPK inhibition. Cetuximab is a monoclonal antibody that binds to the extracellular domain of the Epidermal Growth Factor Receptor (EGFR). The combination aims to achieve deeper and more durable responses in colorectal cancer patients who have progressed on standard EGFR-targeted therapies by simultaneously blocking multiple nodes of the RAS/MAPK signaling pathway and its bypass mechanisms.
- Other names
- avutometinib + defactinib + cetuximab combination therapy
02
Targets
EGFR (Epidermal growth factor receptor)FAK (Focal adhesion kinase)Mitogen-activated protein kinase kinase 1 and 2 within RAF/MEK complexesARAF (Proto-oncogene serine/threonine-protein kinase A-Raf)BRAF (B-Raf proto-oncogene, serine/threonine kinase)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)RAF1 (c-Raf-1 (Y340D/Y341D))
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