Phase II Investigation of Pembrolizumab in Combination With Bevacizumab and Oral Cyclophosphamide in Patients With High Grade Ovarian Cancer and Surgically Documented Minimal Residual Disease After Frontline Therapy

Inclusion Criteria: Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of high grade non-mucinous epithelial ovarian cancer will be enrolled in this study. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days after the last dose of study medication. The participant provides written informed consent for the trial. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention. Have received standard of care frontline surgical and chemotherapy treatment (at least six cycles of platinum and taxane (or equivalent, with or without bevacizumab/biosimilar therapy). Patients who received neoadjuvant therapy are included. Have undergone a second-look surgery after achieving a complete clinical response to frontline surgery and adjuvant chemotherapy as evidenced by (a) normal physical exam, (b) normal CT or PET-CT of abdomen and pelvis or other equivalent imaging, and (c) normalization of CA-125 (unless the patient has an elevated CA-125 thought to be due to other confounding causes by the treating physician). CT scans with subtle or indeterminate findings will not disqualify participation. Histologically confirmed residual ovarian cancer at time of second-look surgery. Patients with cytological evidence of malignant cells in washings obtained as part of the second look procedure are eligible even if biopsies are negative. Subjects must have germline BRCA1 and 2 non-mutated AND homologous recombination proficient (HRP aka HRD negative) tumors, as determined by testing using MyChoice by Myriad Genetics (or other CLIA certified lab per PI's discretion). Subjects with HRD indeterminate status due to failed testing or insufficient tissues are eligible. Subjects with BRCA1/2 variants of uncertain significant (VUS) are eligible as long as they are HRD negative. Note germline mutation and HRD tests are performed as standard of care in all women with newly diagnosed advanced stage ovarian cancer and the testing itself is not part of the protocol. Be willing to allow use of archival tissue from second-look surgery and primary surgery or biopsy for use in this study. Have adequate organ function as determined by the following laboratory values: ANC ≥ 1,000 /mcL Platelets ≥ 100,000 / mcL Hgb ≥8 g/dL (transfusion allowed) Creatinine Clearance ≥40 mL/min (measured or calculated per local practice) Total Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of suspected/documented Gilbert's Syndrome AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Have adequately recovered from second look surgery to be able to start the investigational regimen no sooner than 28 days from the date of second look surgery, and within 7 weeks of this procedure. Negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (unless surgically sterile or postmenopausal for greater than one year). Exclusion Criteria: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. Is currently receiving or has received an investigational agent within 4 weeks prior to the first dose of study intervention. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Steroids to reduce risk of radiologic contrast allergy is permitted. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV) infection. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Has had an allogenic tissue/solid organ transplant. Inadequately controlled hypertension as defined by SBP>150 or DBP>90 on at least two separate occasions documented in the medical record. Patients would be eligible if blood pressure controlled is achieved with appropriate anti-hypertensive therapy. Rescreening after this therapy has been instituted is allowed. Histology showing mucinous or low-grade epithelial ovarian carcinoma. Documented deleterious germline or somatic BRCA mutations or tumors known to be homologous recombination deficiency (HRD) positive (e.g. as determined by MyChoice by Myriad Genetics (or other CLIA certified labs per PI's discretion). History of arterial thrombosis. Patients with history of DVT are eligible as long as they have received or are receiving appropriate anticoagulation therapy. History of gastrointestinal or urinary fistulae, non-healed or chronic wound, or other conditions that, in the investigator's view, would contraindicate or significantly increase the risks of bevacizumab/biosimilar therapy. History of known hemoptysis, gastrointestinal or intracerebral hemorrhage. Unable to understand or to comply with the study instructions and requirements or has a history of non-compliance to the medical regimen. Concurrent or planned use of any other anti-cancer systemic chemotherapy, biological therapy (including hormonal or immune therapy), radiation therapy, or live cancer vaccines. Any other medical condition that in the investigator's judgement would significantly increase the risks of the investigational regimen.