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 <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
- 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 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
- 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
