A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer

This trial is testing the combination of avutometinib (VS-6766) and defactinib — two investigational drugs that block abnormal cell signaling pathways (MEK/RAF and FAK, respectively) — for women with gynecologic mesonephric or mesonephric-like cancer (GMC), an aggressive and rare subtype of gynecologic cancer that is often resistant to standard chemotherapy. By targeting two pathways simultaneously, researchers aim to prevent tumor cells from finding escape routes and becoming resistant. Female patients aged 18 and older with histologically confirmed, measurable, persistent or recurrent GMC are eligible. Patients may have had any number of prior treatment lines, including none. Pregnant patients, those with unresectable newly diagnosed localized disease, those on warfarin, or those with prior MEK/RAF/FAK inhibitor treatment are excluded, among others. Participants will receive both drugs orally on a specific schedule and be monitored for tumor response and side effects. For women with this rare and challenging cancer, a targeted combination approach represents a scientifically rational and potentially important new treatment option — and clinical trials are the essential path to establishing whether it works.