avutometinib — Investigational Agent
Other · Phase 2 · Verastem Oncology / Jazz Pharmaceuticals
Mechanism of Action
Dual RAF/MEK clamp inhibitor that simultaneously inhibits MEK kinase catalytic activity AND prevents the feedback-driven reactivation of MEK by blocking MEK-to-RAF scaffolding interactions. Conventional selective MEK inhibitors (e.g., trametinib) trigger paradoxical RAS/RAF pathway rebound through relief of negative feedback, limiting their single-agent efficacy. Avutometinib disrupts this rebound by physically clamping RAF and MEK together in an inactive complex, providing more durable RAS/MAPK pathway suppression. Often combined with defactinib (a FAK inhibitor) to block a parallel…
Investigational Indications
- Low-grade serous ovarian carcinoma (LGSOC) — including recurrent disease
- KRAS-mutant non-small cell lung cancer (NSCLC)
- KRAS-mutant colorectal cancer (CRC)
- KRAS-mutant pancreatic ductal adenocarcinoma
- NF1-mutant tumors
- Other RAS/MAPK pathway-driven solid tumors