A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer

Patients may be eligible for inclusion in the study if they meet the following criteria:

• Histologically proven LGSOC (ovarian, fallopian, peritoneal)
• Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
• Measurable disease according to RECIST v1.1.
• An Eastern Cooperative Group (ECOG) performance status ≤ 1.
• Adequate organ function
• Adequate recovery from toxicities related to prior treatments.
• For patients with reproductive potential, Agreement to use highly effective method of contraceptive.
• Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures

Patients will be excluded from the study if they meet any of the following criteria:

• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
• Co-existing high-grade ovarian cancer or another histology.
• Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
• History of prior malignancy with recurrence <3 years from the time of enrollment.
• Major surgery within 4 weeks.
• Symptomatic brain metastases or spinal cord compression.
• An active skin disorder that has required systemic therapy within one year of signing informed consent.
• History of medically significant rhabdomyolysis.
• For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor.
• Symptomatic bowel obstruction within 3 months.
• Concurrent ocular disorders.
• Concurrent heart disease or severe obstructive pulmonary disease.
• Subjects with the inability to swallow oral medications.
• Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.