A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients

A Phase 2 Study of Avutometinib (VS-6766, a Dual RAF/MEK Inhibitor) In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) in Japanese Patients

This study will confirm the safety and efficacy of avutometinib in combination with defactinib in Japanese patients with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

This is a multi-center, open label Phase 2 study designed to evaluate safety and tolerability and confirm efficacy by BICR of avutometinib in combination with defactinib in Japanese patients with molecularly profiled recurrent LGSOC.

Inclusion Criteria:

• Histologically proven LGSOC (ovarian, peritoneal)
• Documented mutational status of KRAS by validated diagnostic test of tumor tissue
• Documented disease progression (radiographic or clinical) or recurrence of LGSOC and have received at least one platinum-based chemotherapy agent
• Measurable disease according to RECIST 1.1
• An Eastern Cooperative Group (ECOG) performance status ≤ 1.
• Adequate organ function
• Adequate recovery from toxicities related to prior treatments
• Agreement to use highly effective method of contraceptive, if necessary

Exclusion Criteria:

• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
• Co-existing high-grade ovarian cancer or another histology
• History of prior malignancy, excluding ovarian cancer, with recurrence <3 years from the time of enrollment
• Major surgery within 4 weeks
• Symptomatic brain metastases requiring steroids or other interventions
• Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
• For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
• Active skin disorder that has required systemic therapy within the past year
• History of rhabdomyolysis
• Concurrent ocular disorders
• Concurrent heart disease or severe obstructive pulmonary disease
• Patients with the inability to swallow oral medications