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Completed
NCT03740165
Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)
Conditions: Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Neoplasms
Sex: Female
Ages: 18 Years – N/A
Healthy volunteers: No
Phase: PHASE3
Enrollment: 1367
Sponsor: Merck Sharp & Dohme LLC
Location: University of Alabama at Birmingham (UAB) ( Site 0036) Birmingham Alabama
Summary
The purpose of this study is to assess the efficacy and safety of treatment with carboplatin/paclitaxel\* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer.
The primary study hypotheses are that the combination of pembrolizumab plus carboplatin/paclitaxel\* followed by continued pembrolizumab and maintenance olaparib is superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in participants with programmed death-ligand 1 (PD-L1) positive tumors (Combined Positive Score \[CPS\]≥10) and in all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect to PFS per RECIST 1.1 in participants with PD-L1 positive tumors (CPS≥10) and in all participants.
Eligibility Criteria
Inclusion Criteria:
* Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
* Has just completed primary debulking surgery or is eligible for primary debulking surgery or is a potential candidate for interval debulking surgery
* Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
* Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125) (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
* Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor markers status prior to randomization
* 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
* Female participants are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) Is a WOCBP and using a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, 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 in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test 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, a serum pregnancy test is required. 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
* Has adequate organ function
Exclusion Criteria:
* Has mucinous, germ cell, or borderline tumor of the ovary
* Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
* Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
* Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
* Has a known additional malignancy that is progressing or has required active treatment in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical carcinoma in situ) that has undergone potentially curative therapy are not excluded.
* Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period
* Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to randomization. Stable brain metastases should be established prior to the first dose of study medication lead-in chemotherapy
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* Has a known history of active tuberculosis (TB; Bacillus Tuberculosis)
* Has an active infection requiring systemic therapy
* Has received colony-stimulating factors (eg, granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor \[GM-CSF\] or recombinant erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in period
* Is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
* Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer \
Source: ClinicalTrials.gov (NCT03740165). StuddyBuddy aggregates publicly available trial information.