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