Pembrolizumab in Combination with Bevacizumab and Pegylated Liposomal Doxorubicin in Patients with Ovarian Cancer

Exclusion Criteria

• •1. Platinum refractory cancers, defined as lack of response to salvage treatment with a disease recurrence during the first line platinum-based chemotherapy.
• •2. Patients with PLD-resistant EOC, as evidenced by lack of response or progression within 6 months of the last dose of PLD.
• •3. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period.
• •4. Has had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• •Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• •5. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
• •6. Major surgery within 30 days or bowel resection at cytoreductive surgery within 6 months before the initiation of study treatment.
• •7. Non-healing wound or significant traumatic injury within 30 days before the initiation of study treatment.
• •8. Any previous radiotherapy to the abdomen or pelvis.
• •9. Previous Cerebro-Vascular Accident, Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage.
• •10. History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to inclusion, and known inherited (genetic) predisposition to thrombosis (such as deficit in protein C/S) or acquired predisposition to thrombosis (such as anti-phospholipid syndromes)
• •11. Prior history of hypertensive crisis or hypertensive encephalopathy.
• •12. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •13. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy within 2 years prior to inclusion.
• •14. Has known symptomatic active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• •15. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• •16. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active pneumonitis.
• •17. Has an active infection requiring systemic therapy.
• •18. Has a Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• •19. 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
• •20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •21. Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of trial treatment
• •22. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• •23. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
• •24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •25. Patient under guardianship or deprived of his liberty by a judicial or administrative decision
• •26. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective ethic approval (by chair or designee) is given allowing exception to this criterion for a specific subject.