A Phase 3, Randomized, Open-Label Study of Combination Therapy with Avutometinib plus Defactinib Versus Investigator's Choice of Treatment in Patients with Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

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

1. Histologically proven LGSOC (ovarian, fallopian, peritoneal)
2. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
3. Measurable disease according to RECIST v1.1.
4. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
5. Adequate organ function
6. Adequate recovery from toxicities related to prior treatments.
7. For patients with reproductive potential, Agreement to use highly effective method of contraceptive.
8. 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:

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