A Study of Avutometinib, Defactinib, and Letrozole in People With Low-Grade Serous Ovarian Cancer

Inclusion Criteria: * Female patients ≥ 18 years of age * Histologically-confirmed LGSOC (ovarian, peritoneal) by tissue biopsy read by pathology at study institution. NOTE: Patients with a prior history of serous borderline tumors without prior systemic (cytotoxic or hormonal) treatment but a new diagnosis of low-grade serous ovarian cancer are eligible. * Determination that the patient is not a primary surgical candidate by a gynecologic oncologist surgeon; or has undergone an attempted primary debulking with residual RECIST measurable disease. * Measurable disease according to RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. Each lesion must be ≥10mm when measured by CT or MRI. Lymph nodes must be ≥15mm by short axis when measured by CT or MRI. * An Eastern Cooperative Group (ECOG) performance status of ≤1. Patients with an ECOG performance status of 2 are permitted on trial if this is deemed to be secondary to cancer but not to other comorbidities. * Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression. Patients with asymptomatic brain metastases that do not require intervention are also eligible. * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV v…