Phase II Study of Pembrolizumab and Bevacizumab in Combination With Platinum-based Chemotherapy Followed by Pembrolizumab, Bevacizumab and Olaparib in Patients With Platinum-sensitive Recurrent Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- pembrolizumab
- Conditions
- Carcinoma, Ovarian Epithelial
- Sponsor
- Kosei Hasegawa, MD, PhD
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Two-year progression-free survival rate
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
This trial is a multicenter, single-arm, phase II study evaluating the efficacy of pembrolizumab and bevacizumab in combination with platinum-based chemotherapy (PBC) followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.This study is planned to enroll eligible 35 patients from multiple study sites in Japan.
Investigators
Kosei Hasegawa, MD, PhD
Professor and Director, Department of Gynecologic Oncology
Saitama Medical University International Medical Center
Eligibility Criteria
Inclusion Criteria
- •Participant is at least 20 years of age on the day of signing informed consent with histologically confirmed epithelial ovarian cancer (excluding borderline ovarian tumor) excluding mucinous carcinoma.
- •Participant has received only one regimen of PBC (3 cycles or more) as prior therapy with clinical CR (determined by negative clinical examination and a normal CA-125 level).
- •Participant has documentation of progressive disease at least 6 months from completion of PBC (platinum-sensitive).
- •Participant with measurable disease based on RECIST 1.1 at screening
- •Participant is able to provide a core or excisional biopsy of a tumor for testing of PD-L1 status, etc.
- •Participant with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 at the screening
- •Participant has a life expectancy of at least 12 weeks as determined by the investigators.
- •Participant has adequate organ function.
Exclusion Criteria
- •A Women of Childbearing Potential (WOCBP) who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Participant 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).
- •Participant has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of study drug.
- •Participant has received prior radiotherapy within 2 weeks of the first dose of study drug.
- •Participant has received major surgery within 4 weeks prior to the first dose of study drug.
- •Participant 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.
- •Participant is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug.
- •Participant 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.
- •Participant has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •Participant has known active CNS metastases and/or carcinomatous meningitis.
Arms & Interventions
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: pembrolizumab
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: olaparib
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: bevacizumab
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: carboplatin
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: paclitaxel
pembrolizumab and bevacizumab with PBC followed by pembrolizumab, bevacizumab and olaparib
Participants will continue treatment period up to 6 cycles and enter maintenance period after treatment period. Study treatment will be continued until progressive disease (PD) based on RECIST 1.1, death, unacceptable toxicity, or participant withdrawal from the study.
Intervention: docetaxel
Outcomes
Primary Outcomes
Two-year progression-free survival rate
Time Frame: 2 years
Two-year progression-free survival rate after administration of pembrolizumab and bevacizumab in combination with PBC followed by pembrolizumab, bevacizumab and olaparib as a maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer based on RECIST 1.1.
Secondary Outcomes
- Overall Survival (OS)(3 years)
- Progression-Free Survival (PFS)(3 years)
- Disease Control Rate (DCR)(3 years)
- One-year progression-free survival rate(1 year)
- Incidence of adverse events(3 years)
- PFS in maintenance period by chemotherapy responder(3 years)
- Objective Response Rate (ORR)(3 years)
- Duration of Response (DOR)(3 years)