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

• •1. 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.
• •2. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• •1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
• •2. 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.
• •3. The participant provides written informed consent for the trial.
• •4. 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.
• •5. 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. Omission of one or more doses of chemo for toxicity or hypersensitivity reaction is allowed. Have minimal residual disease (MRD) after a complete clinical response to frontline therapy (defined as: having a normalization of CA-125 and no obvious evidence of disease on exam or imaging unless the patient has an elevated CA-125 thought to be due to other confounding causes by the treating physician). Imaging with subtle or indeterminate findings will not disqualify participation.
• •6. Having MRD is defined as either of the following conditions (must occur within 3 months on the last dose of frontline platinum-taxane chemotherapy):
• •1. Second-look surgery that may be performed either as standard of care or in the context of a non-therapeutic clinical trial with positive tissue or cytology.
• •OR
• •2. Detectable ctDNA by the Signatera assay. Assay results that are "positive below analytical range" qualify as detectable.
• •7. Participants who have undergone second look surgery, must have 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.
• •8. Be willing to allow use of archival tissue from second-look surgery (if performed) and primary surgery or biopsy for use in this study.
• •9. Have adequate organ function as determined by the following laboratory values:
• •1. ANC ≥ 1,000 /mcL
• •2. Platelets ≥ 100,000 / mcL
• •3. Hgb ≥8 g/dL (transfusion allowed)
• •4. Creatinine Clearance ≥30 mL/min (measured or calculated per local practice)
• •5. Total Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of suspected/documented Gilbert's Syndrome
• •6. AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
• •10. 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.
• •11. 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).
• •18. Histology showing mucinous or low-grade epithelial ovarian carcinoma.
• •19. 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).
• •20. History of arterial thrombosis (pulmonary embolism in pulmonary arteries do not count as arterial thrombosis). Patients with history of DVT are eligible as long as they have received or are receiving appropriate anticoagulation therapy.
• •21. 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.
• •22. Unable to understand or to comply with the study instructions and requirements or has a history of non-compliance to the medical regimen.
• •23. Concurrent or planned use of any other anti-cancer systemic chemotherapy, biological therapy (including hormonal or immune therapy), radiation therapy, or live cancer vaccines.
• •24 Any other medical condition that in the investigator's judgement would significantly increase the risks of the investigational regimen.