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Clinical Trial 20070

Cancer Type: Genitourinary
Interventions:Enzalutamide (); Pembrolizumab (Keytruda); Placebo ()

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Julie Kish

Call 813-745-6100
or 1-800-679-0775
Overview

Study 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)

Summary

The purpose of this study is to test the safety of the study drugs, pembrolizumab in combination with a hormone drug (enzalutamide) for prostate cancer,

Objective

Primary: To compare pembrolizumab plus enzalutamide versus placebo plus enzalutamide with respect to OS Hypothesis (H1): The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to OS To compare pembrolizumab plus enzalutamide versus placebo plus enzalutamide with respect to rPFS per PCWG-modified RECIST 1.1 as assessed by BICR where soft-tissue will be assessed per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and bone disease will be assessed per PCWG criteria Secondary: To compare pembrolizumab plus enzalutamide versus placebo plus enzalutamide with respect to TFST To compare pembrolizumab plus enzalutamide versus placebo plus enzalutamide with respect to the: PSA response rate PSA undetectable rate { ORR and DOR per PCWGmodified RECIST 1.1 as assessed by BICR

Inclusion Criteria

  • 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 >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.

  • 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 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 severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its 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 170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
  • Has bradycardia (heart rate of > Has history of prostate cancer progression on ketoconazole
  • Has had prior treatment with enzalutamide, apalutamide, or darolutamide
  • 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