Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer (OPEB-01)

Yonsei University

Status and phase

Invitation-only

Phase 2

Conditions

Platinum-sensitive Recurrent BRCA Wild Type Ovarian Cancer

Treatments

Drug: Olaparib-Pembrolizumab-Bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04361370

4-2020-0386

Details and patient eligibility

About

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.

Full description

'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)

Enrollment

44 estimated patients

Sex

Female

Ages

20+ years old

Volunteers

No Healthy Volunteers

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:
1. ANC≥1500/µL
2. PLT≥100 000/µL
3. Hemoglobin≥9.0 g/dL or ≥5.6 mmol/L
4. Creatinine≤1.5 × ULN or calculated creatinine clearance≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
5. Total bilirubin≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
6. AST (SGOT) and ALT (SGPT)≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
7. 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