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

Status: Active

Description

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)

Eligibility Criteria

Inclusion Criteria

  • 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 prior to 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 disease that progressed during or after treatment with abiraterone acetate OR enzalutamide, but not both, for mCRPC
  • Has received no more than 1 previous chemotherapy regimen for mCRPC and have had PD during treatment
  • 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 prior to randomization
  • Must agree to refrain from donating sperm during the intervention period and for at least 180 days thereafter PLUS Be abstinent from heterosexual intercourse OR Agree to use contraception unless confirmed to be azoospermic AND Also agree to use a male condom when engaging in any activity that allows passage of ejaculate to another person of any sex
  • 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

Exclusion Criteria

  • 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 severe (≥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) prior to randomization
  • Has received prior treatment with olaparib or any other PARP inhibitor
  • Has received prior treatment with apalutamide or darolutamide
  • Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) prior to 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 prior to 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 180 days after the last dose of study intervention

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Sarah Rosales
Phone: 310-794-7686
Email: srosales@mednet.ucla.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: In review
Name Not Available

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Merck and Company Inc

Trial IDs

Primary ID 7339-010
Secondary IDs NCI-2019-02382, 194832, MK-7339-010, 2018-004118-16, KEYLYNK-010
Clinicaltrials.gov ID NCT03834519