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avutometinib + defactinib + everolimus
- Development stage
- Phase 1
- Lead developer
- Verastem Oncology
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This triplet combination therapy consists of avutometinib (a RAF/MEK clamp), defactinib (a focal adhesion kinase inhibitor), and everolimus (an mTOR inhibitor). Avutometinib, also known as VS-6766, inhibits the RAS/MAPK signaling pathway by binding to both RAF and MEK proteins, effectively clamping them in an inactive state. Defactinib targets focal adhesion kinase (FAK) to potentially overcome resistance mechanisms in the tumor microenvironment. Everolimus inhibits the PI3K/AKT/mTOR pathway. This combination is being investigated in a Phase Ib dose escalation and expansion study led by M.D. Anderson Cancer Center for patients with recurrent RAS pathway mutant endometrial cancer, aiming to evaluate safety, tolerability, and the recommended Phase 2 dose.
- Other names
- VS-6766 + VS-6063 + everolimus
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)RAF1 (c-Raf-1 (Y340D/Y341D))FKBP1AMEK2 (Dual specificity mitogen-activated protein kinase kinase 2)FAK (Focal adhesion kinase)PTK2BMechanistic target of rapamycin complex 1MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)
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