Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

Summary

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and enzalutamide in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve, or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Radiographic Progression-free Survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review.

Official Title

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-641)

Keywords

Prostatic Neoplasms Programmed Cell Death-1 (PD1, PD-1) Programmed Death-Ligand 1 (PDL1, PD-L1) Pembrolizumab Enzalutamide Pembrolizumab + Enzalutamide

Eligibility

You can join if…

Open to males ages 18 years and up

  • Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
  • Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization
  • Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
  • Is abiraterone-naive or are intolerant to/progressed on abiraterone
  • Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
  • Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
  • Participants must agree to the following during the study treatment period and for ≥120 days after the last dose of study treatment: Refrain from donating sperm PLUS Use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
  • Participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
  • Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in 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 CAN'T join 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 past 2 years
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  • Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
  • Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
  • Has an active infection (including tuberculosis) requiring systemic therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
  • 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 hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
  • Has bradycardia (heart rate of <50 beats per minute) on the screening electrocardiogram (ECG)
  • Has history of prostate cancer progression on ketoconazole
  • Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate
  • Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
  • Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
  • Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization
  • Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization
  • Has received a live vaccine within 30 days prior to 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 first dose of study treatment
  • Has a "superscan" bone scan
  • Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
  • Has had an allogenic tissue/solid organ transplant

Locations

  • UCLA Department of Medicine - Hematology & Oncology ( Site 0081) accepting new patients
    Santa Monica California 90404 United States
  • St. Joseph Heritage Healthcare ( Site 0069) accepting new patients
    Fullerton California 92835 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Merck Sharp & Dohme Corp.
Links
Merck Oncology Clinical Trial Information
ID
NCT03834493
Phase
Phase 3
Study Type
Interventional
Last Updated