defactinib — Investigational Agent
Other · Phase 2 · Verastem Oncology / Jazz Pharmaceuticals
Mechanism of Action
Oral, selective ATP-competitive inhibitor of focal adhesion kinase (FAK, encoded by PTK2) and the related proline-rich tyrosine kinase 2 (PYK2). FAK is a non-receptor tyrosine kinase that integrates signals from integrins and growth factor receptors to drive cell survival, adhesion, migration, and the maintenance of cancer stem cells, and it also promotes an immunosuppressive tumor microenvironment. In RAS/MAPK-driven tumors, FAK activation is a key parallel escape mechanism that reactivates PI3K/AKT and YAP-dependent survival signaling when the MEK/RAF axis is suppressed. Defactinib is…
Investigational Indications
- Recurrent low-grade serous ovarian carcinoma (LGSOC) — in combination with avutometinib
- KRAS-mutant non-small cell lung cancer (NSCLC) — in combination with avutometinib
- KRAS-mutant colorectal cancer (CRC) — in combination with avutometinib
- KRAS-mutant pancreatic ductal adenocarcinoma — combination strategies
- Malignant pleural mesothelioma (historical single-agent maintenance studies)