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)

  • STATUS
    Recruiting
  • End date
    Aug 8, 2025
  • participants needed
    1086
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 9 January 2021
Investigator
Toll Free Number
Primary Contact
Kaiser Permanente Oncology Clinical Trial - Walnut Creek ( Site 0080) (2.8 mi away) Contact
+248 other location
paclitaxel
cancer
tumor markers
carboplatin
pembrolizumab
bevacizumab
docetaxel
solid tumors
cancer chemotherapy
solid tumour
olaparib
ovarian cancer
BRCA1/2
BRCA1
fallopian tube
mk-3475
ovarian epithelial cancer
cancer antigen 125
excisional biopsy
carcinosarcoma
carboplatin/paclitaxel
peritoneal cancer
primary peritoneal carcinoma
tumor debulking
ovarian epithelial carcinoma
cancer of the ovary
fallopian tube cancer
epithelial ovarian cancer
debulking surgery
primary debulking surgery
interval debulking surgery

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) and/or Overall Survival (OS), 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 and/or OS.

Description

Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel*, participants will be randomly assigned in to one of three treatment

arms
  • Pembrolizumab+Olaparib,
  • Pembrolizumab+Placebo for Olaparib
  • Placebo for Pembrolizumab+Placebo for Olaparib
  • At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected:
    1. up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle
    2. up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or
    3. up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle.

Docetaxel may be considered for participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after consultation with the Sponsor. The recommended dose as determined by the Scottish Gynaecological Cancer Trials Group is Docetaxel 75 mg/m^2 Q3W plus carboplatin AUC 5 Q3W.

Details
Treatment docetaxel, carboplatin, Paclitaxel, bevacizumab, Pembrolizumab, olaparib, Placebo for Pembrolizumab, Placebo for olaparib
Clinical Study IdentifierNCT03740165
SponsorMerck Sharp & Dohme Corp.
Last Modified on9 January 2021

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Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: ovarian tumors or cancer ovarian or Digestive System Neoplasms or Fallopian Tube Cancer or cancer, ovarian or Recurrent Ovarian Cancer or cancer of th...?
Do you have any of these conditions: Ovarian Function or Neoplasm of unspecified nature of digestive system or ovarian carcinomas or cancer ovarian or ovarian tumors or cancer, ovarian or...?
Do you have any of these conditions: cancer of the ovary or cancer, ovarian or Peritoneal Neoplasm or Fallopian Tube Cancer or ovarian tumors or Ovarian Cancer or Ovarian disorder or Abdo...?
Do you have any of these conditions: cancer ovarian or cancer, ovarian or Abdominal Cancer or ovarian tumors or Peritoneal Neoplasm or Recurrent Ovarian Cancer or Abdominal Neoplasm or Ov...?
Do you have any of these conditions: Ovarian disorder or fallopian tube cancers or Ovarian Cancer or Neoplasm of unspecified nature of digestive system or ovarian carcinomas or cancer, ov...?
Do you have any of these conditions: Digestive System Neoplasms or Recurrent Ovarian Cancer or Abdominal Cancer or Peritoneal Neoplasm or Abdominal Neoplasm or cancer of the ovary or canc...?
Do you have any of these conditions: cancer of the ovary or fallopian tube cancers or Recurrent Ovarian Cancer or Neoplasm of unspecified nature of digestive system or Abdominal Cancer or...?
Do you have any of these conditions: ovarian tumors or fallopian tube cancers or cancer ovarian or Ovarian Cancer or cancer of the ovary or Abdominal Cancer or Recurrent Ovarian Cancer or...?
Do you have any of these conditions: cancer, ovarian or Ovarian Cancer or cancer of the ovary or Ovarian disorder or Neoplasm of unspecified nature of digestive system or Recurrent Ovaria...?
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Fallopian Tube Cancer or ovarian carcinomas or ovarian tumors or Abdominal Neoplasm or Digestive System Neoplasms or Ovarian disorder or Recurrent Ova...?
Do you have any of these conditions: cancer, ovarian or Ovarian Cancer or Digestive System Neoplasms or ovarian tumors or Recurrent Ovarian Cancer or Peritoneal Neoplasm or Abdominal Canc...?
Do you have any of these conditions: ovarian tumors or Ovarian Cancer or Ovarian Function or Recurrent Ovarian Cancer or ovarian carcinomas or fallopian tube cancers or cancer, ovarian or...?
Do you have any of these conditions: Recurrent Ovarian Cancer or Abdominal Neoplasm or cancer, ovarian or Ovarian disorder or ovarian tumors or Ovarian Cancer or Peritoneal Neoplasm or ca...?
Do you have any of these conditions: ovarian carcinomas or Ovarian disorder or fallopian tube cancers or Peritoneal Neoplasm or Abdominal Cancer or Abdominal Neoplasm or Recurrent Ovarian...?
Do you have any of these conditions: fallopian tube cancers or Recurrent Ovarian Cancer or Ovarian Cancer or ovarian tumors or cancer ovarian or Digestive System Neoplasms or Abdominal Ca...?
Do you have any of these conditions: Peritoneal Neoplasm or Abdominal Neoplasm or Fallopian Tube Cancer or Recurrent Ovarian Cancer or Ovarian Cancer or Ovarian Function or Ovarian disord...?
Are you female?
Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (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
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 180 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered) and agrees not to donate eggs (ova, oocytes) to others or freeze/store for personal 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 <6 months prior to screening
Has a known history of human immunodeficiency virus (HIV) infection
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. Testing for hepatitis B or hepatitis C is required at screening only if mandated by local health authority. Note: Participants with a history of hepatitis B but who are HBsAg negative are eligible for the study
Is either unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption)
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. Note: This applies only to participants who will receive bevacizumab during the lead-in period and should be confirmed prior to the first administration of bevacizumab. Use of antihypertensive medications to control blood pressure is allowed
Has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or GI perforation, related to underlying EOC (for participants receiving bevacizumab)
Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to randomization (for participants receiving bevacizumab)
Is 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 Day 1 of Cycle 1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study, starting with screening through 180 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered)
Has received prior treatment for any stage of OC, including radiation or systemic anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, investigational therapy)
Has received prior therapy with an anti-Programmed Cell Death-1 (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 (e.g. cytotoxic T lymphocyte antigen-4 [CTLA-4], OX 40, CD137)
Has received prior therapy with either olaparib or any other poly(adenosine-ribose) polymerase (PARP) inhibitor
Has intraperitoneal chemotherapy planned or has been administered as first-line therapy
Has received a live vaccine within 30 days prior to the first dose of study treatment on Day 1 of Cycle 1
Has severe hypersensitivity (Grade 3) to pembrolizumab, olaparib, carboplatin, paclitaxel or bevacizumab (if using) and/or any of their excipients
Is currently receiving either strong (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
Has received whole blood transfusions in the last 120 days prior to randomization
Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks (28 days) of starting chemotherapy in the Lead-in Period
Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions or participant has congenital long QT syndrome
Has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation
Either has had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery
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