Avutometinib + Defactinib (RAF-MEK clamp / FAK blocker) Posts 42% ORR and 20 mo PFS in Refractory Low-Grade Serous OC (LGSOC)

In the first-in-human phase 1 FRAME trial (NCT03875820), 26 heavily pre-treated low-grade serous ovarian cancer patients received intermittent avutometinib 3.2 mg once daily (BIW, 3-weeks-on/1-off) plus continuous defactinib 200 mg BID. Investigator-assessed ORR reached 42% and median PFS was 20.1 months; pharmacokinetics/pharmacodynamics matched single-agent profiles, and the staggered schedule aimed to curb class-typical rash and GI AEs (grade 3+ rates not yet detailed). For context, single-agent trametinib—the current targeted benchmark—achieved 26% ORR and 13 mo PFS in the GOG 281/LOGS study, underscoring a potentially meaningful efficacy bump with dual RAF-MEK/FAK blockade.