Overview

Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)

Status:
Recruiting
Trial end date:
2025-02-28
Target enrollment:
0
Participant gender:
Male
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Merck Sharp & Dohme Corp.
Treatments:
Pembrolizumab
Criteria
The main inclusion and exclusion criteria include but are not limited to the following:

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)

- Has met one of the following criteria with regard to abiraterone acetate exposure: (1)
is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of
mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3)
received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed
on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with
bone progression)

- 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 ≥45
days after the last dose of enzalutamide: EITHER be abstinent OR must agree to use
male condom

- 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 (noninfectious) pneumonitis that required steroids or current
pneumonitis/interstitial lung disease

- Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B
virus (HBV) or known active 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 or live attenuated 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 90 days after the last dose of
enzalutamide

- Has had an allogenic tissue/solid organ transplant