First-line chemotherapy plus pembrolizumab and olaparib for BRCA non-mutated advanced EOC
- Conditions
- Advanced epithelial ovarian cancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001973-25-DE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 1284
1. Participant has histologically confirmed FIGO Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, (any grade), carcinosarcoma, mixed mullerian with highgrade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
2. Participant has just completed primary debulking surgery or is eligible for primary debulking surgery or is a potential candidate for interval debulking surgery. 3. Participant is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
4. Participant that is a candidate for neoadjuvant chemotherapy has a CA-125 (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and PD-L1
status prior to randomization
6. Participant is female and at least 18 years of age on the day of signing informed consent
7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the Lead-in Period and within 3 days prior to Day 1 of Cycle 1.
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
•Is not a woman of childbearing potential (WOCBP) OR
•Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the Treatment Period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this
period. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study treatment.
• A WOCBP must have a negative highly sensitive pr qegnancy test (urine or serum as required by local regulations) within either 24 hours (urine) or 72 hours (serum) before the first dose of study treatment.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
9. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research; however, the participant may pa
1. Participant has mucinous, germ cell, or borderline tumor of the ovary
2. Participant has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
3. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
4. Participant either has myelodysplastic syndrome (MSD)/acute myeloid leukemia (AML)or has features suggestive of MDS/AML
5. Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years
6. Participant has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the Lead-in Period
7. Participant has known active central nervous system metastases and/or carcinomatous meningitis.
8. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization
9. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years
10. Participant has a known history of active tuberculosis
11. Participant has an active infection requiring systemic therapy
12. Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator
13. Participant has received colony-stimulating factors within 4 weeks (28 days) prior to receiving chemotherapy during the Lead-in Period.
14. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
15. Participant has had surgery <6 months prior to screening to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer.
16. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study
17. Participant has a known history of human immunodeficiency virus (HIV) infection.
18. Participant has a known history of hepatitis B or known active hepatitis C virus infection.
19. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption
20. Participant has uncontrolled hypertension, defined as defined as systolic >140 mm Hg or diastolic >90 mm Hg documented by 2 blood pressure readings taken at least 1 hour apart.
21. Participant has current, clinically relevant bowel obstruction, abdominal fistula or gastrointestinal perforation, related to underlying EOC
22. Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to randomization
23. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to Day1 of Cycle 1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study.
24. Participant has received prior treatment for advanced any stage of OC
25. 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
26. Participant has received prior t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method