Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)

Completed · Phase 3 · Has a placebo group

Conditions studied: Prostatic Neoplasms

In brief

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and docetaxel in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but have progressed on or are intolerant to Next Generation Hormonal Agent (NHA). There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone 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.

Key facts

Study ID

NCT03834506

Run by

Merck Sharp & Dohme LLC

People needed

1030

Starts

2019-05-02

Expected to finish

2023-07-18

Last updated by the study team

2025-07-18

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• 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 screening
• 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 received prior treatment with one (but not more than one) NHA (eg, abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC) and either a) progressed through treatment OR b) has become intolerant of the drug
• 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 at least 120 days after the last dose of pembrolizumab or for at least 180 days after the last dose of docetaxel (whichever is longer): 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 may not qualify 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 severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
• Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to mAbs
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto) prior to randomization
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
• Has hypersensitivity to docetaxel or polysorbate 80
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Has received prior targeted small molecule therapy or abiraterone acetate, enzalutamide, apalutamide, or darolutamide within 4 weeks prior to the first dose of study treatment, or has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to a previously administered agent
• Has received prior radiotherapy to within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
• Has received a live vaccine within 30 days prior to randomization
• Has received treatment with 5α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to randomization
• Has received prior treatment with ketoconazole for prostate cancer
• 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

Where it is running

• St. Joseph Heritage Healthcare ( Site 0069) — Fullerton, California, United States
• University of Southern California Norris Comprehensive Cancer Center ( Site 0061) — Los Angeles, California, United States
• USC Norris Oncology Hematology Newport Beach ( Site 0093) — Newport Beach, California, United States
• University of California San Francisco ( Site 0023) — San Francisco, California, United States
• University of Colorado Cancer Center ( Site 0022) — Aurora, Colorado, United States
• Yale Cancer Center ( Site 0038) — New Haven, Connecticut, United States
• Moffitt Cancer Center ( Site 0080) — Tampa, Florida, United States
• Georgia Cancer Center at Augusta University ( Site 0026) — Augusta, Georgia, United States
• Mount Sinai Hospital Medical Center ( Site 0042) — Chicago, Illinois, United States
• Methodist Hospital- Merriillville ( Site 0008) — Merrillville, Indiana, United States
• Karmanos Cancer Institute ( Site 0077) — Detroit, Michigan, United States
• Henry Ford Health System ( Site 0039) — Detroit, Michigan, United States
• Cancer & Hematology Centers of Western Michigan ( Site 0013) — Grand Rapids, Michigan, United States
• Washington University School of Medicine ( Site 0057) — St Louis, Missouri, United States
• St. Vincent Frontier Cancer Center ( Site 0016) — Billings, Montana, United States
• Nebraska Cancer Specialists ( Site 0034) — Omaha, Nebraska, United States
• Comprehensive Cancer Centers of Nevada ( Site 0092) — Las Vegas, Nevada, United States
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004) — Hackensack, New Jersey, United States
• Associated Medical Professionals of NY ( Site 0060) — Syracuse, New York, United States
• Duke Cancer Center ( Site 0010) — Durham, North Carolina, United States
• W. G. Bill Hefner VA Medical Center ( Site 0029) — Salisbury, North Carolina, United States
• University Hospitals Cleveland Medical Center ( Site 0036) — Cleveland, Ohio, United States
• Oregon Health Sciences University ( Site 0031) — Portland, Oregon, United States
• Carolina Urologic Research Center ( Site 0070) — Myrtle Beach, South Carolina, United States
• University of South Alabama, Mitchell Cancer Institute ( Site 0065) — Mobile, Alabama, United States

Full record on ClinicalTrials.gov

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