Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)

Completed · Phase 3

Conditions studied: Prostatic Neoplasms

In brief

The purpose of this study is to assess the efficacy and safety of the combination of the polyadenosine 5'-diphosphoribose poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and pembrolizumab in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate or enzalutamide (but not both) and to chemotherapy. The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to: 1. Overall Survival (OS) and 2. Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 as assessed by blinded independent central review (BICR) As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable. Participants still on treatment may have the option to continue receiving study intervention or SOC if they are deriving clinical benefit, until criteria for discontinuation are met. Participants who are still on study treatment and deriving clinical benefit will no longer have tumor response assessments by BICR. However, local tumor imaging assessments should continue per standard of care (SOC) schedule. In addition, electronic patient-reported outcome (ePRO) assessments will no longer be performed and biomarker samples will no longer be collected.

Key facts

Study ID

NCT03834519

Run by

Merck Sharp & Dohme LLC

People needed

793

Starts

2019-05-02

Expected to finish

2024-01-27

Last updated by the study team

2025-05-18

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while receiving androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before screening
• Has current evidence of metastatic disease documented by bone lesions on bone scan and/or soft tissue disease shown by computed tomography/magnetic resonance imaging (CT/MRI)
• Has received prior treatment with abiraterone acetate OR enzalutamide, but not both
• Have disease that progressed during or after treatment with abiraterone acetate for either metastatic hormone-sensitive prostate cancer (mHSPC) or mCRP or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression)
• Participants that received abiraterone acetate for mHSPC may not have received abiraterone acetate or enzalutamide for mCRPC
• Have received docetaxel chemotherapy regimen for metastatic castration-resistant prostate cancer (mCRPC) and have had progressive disease during or after treatment with docetaxel
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
• If receiving bone resorptive therapy, including but not limited to bisphosphonates or denosumab, must have been receiving stable doses before randomization
• Must agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic
• Contraception use by men 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 requirement above, the local label requirements are to be followed.
• Has provided tumor tissue from a fresh core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization

You may not qualify if…

• Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis requiring steroids, or has current pneumonitis
• Has known active human immunodeficiency virus (HIV), hepatitis B virus (e.g., hepatitis B surface antigen reactive) or hepatitis C virus (HCV) infection (e.g., HCV RNA [qualitative] is detected)
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has a history of seizure or any condition that may predispose to seizure
• Has a history of loss of consciousness within 12 months of screening
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has (≥Grade 3) hypersensitivity to pembrolizumab and/or any of its excipients
• Has known hypersensitivity to the components or excipients in olaparib, abiraterone acetate, prednisone or prednisolone, or enzalutamide
• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
• Has received an anticancer monoclonal antibody (mAb) before randomization
• Has received prior treatment with olaparib or any other PARP inhibitor
• Has received prior treatment with apalutamide or darolutamide
• Has received prior treatment with enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) before the date of randomization
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• Has received prior treatment 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 (e.g., CTLA-4, OX-40, or CD137)
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 [CYP] (CYP3A4) that cannot be discontinued for the duration of the study
• Has received a previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) or a solid organ transplant
• Has received a live vaccine within 30 days prior to the date of randomization
• Is currently participating in or has participated in a study of an investigational agent, or has used an investigational device, within 4 weeks before the date of randomization
• Has a bone "superscan"
• Is expecting to father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study intervention

Where it is running

• UCLA Hematology/Oncology - Santa Monica ( Site 0081) — Los Angeles, California, United States
• Sibley Memorial Hospital ( Site 0096) — Washington D.C., District of Columbia, United States
• Georgia Cancer Center at Augusta University ( Site 0026) — Augusta, Georgia, United States
• Quincy Medical Group ( Site 0021) — Quincy, Illinois, United States
• Tulane Cancer Center ( Site 0066) — New Orleans, Louisiana, United States
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0005) — Baltimore, Maryland, United States
• Chesapeake Urology Research Associates ( Site 0076) — Towson, Maryland, United States
• Beth Israel Deaconess Medical Ctr. ( Site 0093) — Boston, Massachusetts, United States
• Dana Farber Cancer Institute ( Site 0033) — Boston, Massachusetts, United States
• UMass Memorial Medical Center ( Site 0053) — Worcester, Massachusetts, United States
• Barbara Ann Karmanos Cancer Institute ( Site 0077) — Detroit, Michigan, United States
• Henry Ford Health System ( Site 0039) — Detroit, Michigan, United States
• St. Vincent Frontier Cancer Center ( Site 0016) — Billings, Montana, United States
• Nebraska Cancer Specialists ( Site 0034) — Omaha, Nebraska, United States
• Comprehensive Cancer Centers of Nevada ( Site 0092) — Las Vegas, Nevada, United States
• University of New Mexico Cancer Center ( Site 0048) — Albuquerque, New Mexico, United States
• Memorial Medical Center ( Site 0095) — Las Cruces, New Mexico, United States
• Associated Medical Professionals of NY ( Site 0060) — Syracuse, New York, United States
• Duke Cancer Center Cary ( Site 0010) — Cary, North Carolina, United States
• Gabrail Cancer Center-Research ( Site 0097) — Canton, Ohio, United States
• The Urology Group- Cincinnati ( Site 0094) — Cincinnati, Ohio, United States
• University Hospitals of Cleveland Seidman Cancer Center ( Site 0036) — Cleveland, Ohio, United States
• Carolina Urologic Research Center ( Site 0070) — Myrtle Beach, South Carolina, United States
• Huntsman Cancer Institute ( Site 0002) — Salt Lake City, Utah, United States
• St. Joseph Heritage Healthcare ( Site 0069) — Fullerton, California, United States

Full record on ClinicalTrials.gov

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