Multicenter phase 1 trial of defactinib plus avutometinib in patients with low-grade serous ovarian cancer or other solid tumors

The multicenter phase 1 FRAME trial, at four centers in the UK, evaluated the combination of the RAF-MEK clamp avutometinib and the FAK inhibitor defactinib among patients with low-grade serous ovarian cancer (LGSOC) and other solid tumors. The recommended phase 2 schedule was intermittent dosing of avutometinib and continuous dosing of defactinib, both 3 weeks on and 1 week off. Among the LGSOC patients, the objective response rate was 42.3% (95% CI 23.4-63.1) and the median progression-free survival was 20.1 months (11.2-43.9). The authors conclude that the trial demonstrates the importance of intermittent dosing schedules in combined targeting of MAPK and FAK pathways to improve tolerability, and showed antitumor activity against LGSOC, a tumor relatively resistant to chemotherapy.