Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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This study is phase II, open label, clinical trial to determine the efficacy of Olaparib maintenance with Bevacizumab and Pembrolizumab by assessment progression-free survival(6 months PFS rate) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer.

Detailed Description
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'This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of Olaparib maintenance with Bevacizumab and Pembrolizumab in subjects with platinum-sensitive who have received prior of platinum-based chemotherapy. The study will assess the effectiveness of progression-free survival(6 months PFS rate) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The subject will be treated to until disease progression as below: Maintenance : Olaparib 300mg (twice daily [BID]) Pembrolizumab 200mg every 3 weeks (Q3W) from 2nd infusion for up to 35 infusions Bevacizumab 15mg/kg or 7.5mg/kg every 3 weeks (Q3W)

Official Title
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A Single-arm Phase II Study of Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer (OPEB-01)

Conditions
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Platinum-sensitive Recurrent BRCA Wild Type Ovarian Cancer

Intervention / Treatment
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* Drug: Olaparib-Pembrolizumab-Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 8 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included). Participant has received 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 months' period between penultimate platinum regimen and progression of disease Participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA 1/2 and PD-L1 status prior to enrollment Female participants who are at least 20 years of age and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Participant has adequate organ function as defined in the following: ANC≥1500/µL PLT≥100 000/µL Hemoglobin≥9.0 g/dL or ≥5.6 mmol/L Creatinine≤1.5 × ULN or calculated creatinine clearance≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN Total bilirubin≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT)≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT)≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants Exclusion Criteria: Participant has mucinous, germ cell, or borderline tumor of the ovary Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2 Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis Participant either has myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or has features suggestive of MDS/AML 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 Participant has a known history of active TB (Bacillus Tuberculosis) Participant 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 Participant has uncontrolled hypertension, defined as systolic > 140 mmHg or diastolic > 90 mmHg documented by 2 blood pressure readings taken at least 1 hour apart Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>BRCA mutation wild type, non-mucinous , platinum-sensitive recurrent ovarian cancer | Drug: Olaparib-Pembrolizumab-Bevacizumab<br>* Olaparib 300mg (twice daily [BID]) Pembrolizumab 200mg every 3 weeks (Q3W) from 2nd infusion for up to 35 infusions Bevacizumab 15mg/kg or 7.5mg/kg every 3 weeks (Q3W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival(6 months PFS rate) | To determine the clinical effectiveness of the study treatment assessed using progression free survival(6months) according to RECIST v1.1 criteria (Investigator determined) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | Up to 1year | 
| Time to tumour progression (TTP) |  | Up to 1year | 
| Time to first subsequent treatment(or death) |  | The date of first documented first subsequent treatment or date of death, assessed up to 72 months | 
| Time to second subsequent treatment |  | The date of first documented second subsequent treatment assessed up to 72 months | 
| progression-free survival |  | Up to 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BRCA wild type, ovarian cancer, Platinum-sensitive