A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer

Inclusion Criteria

• •Female patients ≥ 18 years of age
• •Measurable disease according to RECIST 1.1
• •Patients must have persistent (disease that is metastatic at presentation or remains present following first-line therapy) or recurrent disease (disease that has come back or progressed following prior surgery or treatment)
• •Patients with metastatic or recurrent disease do not require any prior systemic therapy prior to enrollment. Patients may have received unlimited lines of prior systemic therapy.
• •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 viral load must be undetectable on suppressive therapy, if indicated.
• •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• •Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for hypothyroidism requiring medication, and alopecia, which must have resolved to Grade ≤2).
• •Female patients with reproductive potential agree to use highly effective method of contraceptive during the trial and for 1 month following the last dose of study intervention. Hormonal forms of contraception are not recommended in this study.
• •Non-hormonal methods of highly effective contraception include:
• •intrauterine device (IUD)
• •bilateral tubal occlusion
• •vasectomized partner
• •sexual abstinence
• •* Patients must have adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO)
• •* Baseline QTc interval \< 460 ms (average of triplicate readings) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block.
• •* Must have adequate organ function defined by the following laboratory parameters:
• •* Total Bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
• •* AST(SGOT)/ALT(SGPT): ≤3 × institutional ULN
• •* Adequate renal function defined as either:
• •Creatinine clearance (CrCL) or estimated Glomerular filtration rate (eGFR) of ≥50 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR).
• •Or:
• •Serum Creatinine ≤ 1.5 x ULN
• •Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
• •Adequate hematologic function including: hemoglobin \[Hb\] ≥ 9.0 g/dL; platelets ≥ 100,000/mm\^3; and absolute neutrophil count \[ANC\] ≥ 1000/mm\^3