Study of Pembrolizumab (MK-3475) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)(MK-3475-199/KEYNOTE-199)
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ClinicalTrials.gov Identifier: NCT02787005 |
Recruitment Status :
Completed
First Posted : June 1, 2016
Last Update Posted : March 8, 2022
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Condition or disease | Intervention/treatment | Phase |
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Metastatic Castration-resistant Prostate Cancer | Biological: Pembrolizumab Drug: Enzalutamide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 388 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199) |
Actual Study Start Date : | July 1, 2016 |
Actual Primary Completion Date : | February 28, 2022 |
Actual Study Completion Date : | February 28, 2022 |

Arm | Intervention/treatment |
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Experimental: Cohort 1: PD-L1 positive with measurable disease
Participants with programmed cell death ligand 1 (PD-L1)-positive, measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.
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Biological: Pembrolizumab
Intravenous infusion
Other Names:
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Experimental: Cohort 2: PD-L1 negative with measurable disease
Participants with PD-L1 negative, measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.
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Biological: Pembrolizumab
Intravenous infusion
Other Names:
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Experimental: Cohort 3: Bone metastases with non-measurable disease
Participants with bone metastases and non-measurable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.
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Biological: Pembrolizumab
Intravenous infusion
Other Names:
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Experimental: Cohort 4: RECIST 1.1-measureable disease
Participants with Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)-measureable disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle and enzalutamide via oral capsules once daily for up to 2 years. The dose of enzalutamide will be the same dose each participant was receiving before the start of pembrolizumab treatment.
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Biological: Pembrolizumab
Intravenous infusion
Other Names:
Drug: Enzalutamide Oral capsules
Other Name: XTANDI® |
Experimental: Cohort 5: Bone metastases only or bone-predominant disease
Participants with bone metastases only or bone-predominant disease receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle and enzalutamide via oral capsules once daily for up to 2 years. The dose of enzalutamide will be the same dose each participant was receiving before the start of pembrolizumab treatment.
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Biological: Pembrolizumab
Intravenous infusion
Other Names:
Drug: Enzalutamide Oral capsules
Other Name: XTANDI® |
- Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by central imaging vendor (Cohorts 1 and 2 combined, Cohort 1, Cohort 2 and Cohort 4) [ Time Frame: Up to 2 years ]
- Disease Control Rate (DCR) (Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined, and by each cohort) [ Time Frame: Up to 2 years ]
- Prostate-specific Antigen (PSA) response rate (Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined, and by each cohort) [ Time Frame: Up to 2 years ]
- Percentage of participants who experience an adverse event (AE) (All cohorts combined and by each cohort) [ Time Frame: Up to 27 months ]
- Percentage of participants who discontinue study drug due to an AE (All cohorts combined and by each cohort) [ Time Frame: Up to 2 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. Disease must be either metastatic or locally confined inoperable disease that cannot be treated with definitive intent (no chance for a curative intervention).
- Has supplied tumor tissue from a newly obtained biopsy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available, from a site not previously irradiated. Participants in Cohorts 1, 2, and 4 with visceral/measurable lesions must provide a newly obtained biopsy performed after the last line of systemic therapy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available. Participants in Cohorts 3 and 5 must at least provide an archival specimen.
For Cohorts 1, 2, and 3 only:
- Has been treated with:
- At least 1 targeted endocrine therapy (defined as second generation antiandrogen therapies that include but are not limited to abiraterone acetate with prednisone, enzalutamide, and next generation targeted agents such as ARN-509).
- At least 1 regimen/line of chemotherapy that contained docetaxel.
- No more than 2 chemotherapy regimens.
- No more than 3 regimens/lines of the aforementioned treatments (having failed/progressed on chemotherapy and targeted endocrine therapy).
For Cohorts 4 and 5 only:
- Failing or showing early signs of failure on current pre-chemotherapy enzalutamide treatment as defined by Prostate Cancer Working Group 3 PCWG3 guidelines. Participants can have failed prior abiraterone treatment before current enzalutamide treatment. Participants must have had a clinically meaningful response to enzalutamide treatment. Enzalutamide must have been initiated no less than 4 weeks prior to the first dose of trial treatment and be continued throughout the study.
For All Cohorts:
- Has documented prostate cancer progression within 6 months prior to screening, as determined by the Investigator, by means of one of the following: 1) PSA progression as defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL, OR, 2) Radiographic disease progression in soft tissue or bone with or without PSA progression
- Has ongoing androgen deprivation with total serum testosterone <50 ng/dL (<2.0 nM).
- Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or Receptor activator of nuclear factor kappa-B ligand [RANK-L inhibitor]) must have been on stable doses for ≥4 weeks prior to first dose of study drug.
- Has a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Participants of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study drug through at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception after the last dose of enzalutamide is 30 days.
- Demonstrates adequate organ function.
Exclusion Criteria:
For All Cohorts:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to mAbs administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or external beam radiation therapy within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to a previously administered agent.
- Has a known additional malignancy that has had progression or has required active treatment in the last 3 years. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Has evidence of interstitial lung disease and/or a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1, anti-PD ligand 1 [anti-PD-L1], and anti-PD-L2 [including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways]).
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has known active Hepatitis B or Hepatitis C.
- Has received a live vaccine within 30 days of planned start of study drug. Any licensed coronavirus disease 2019 (COVID-19) vaccine (including for Emergency use) in a particular country is allowed in the study as long as they are mRNA vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed.
For Cohorts 4 and 5 only:
- Has received prior chemotherapy (e.g., docetaxel) for mCPRC.
- Has any condition (cardiac, neurologic, absorption) other than clinically failing or showing early signs of failure on enzalutamide treatment that would require imminent discontinuation of enzalutamide treatment.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02787005
Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Merck Sharp & Dohme LLC |
ClinicalTrials.gov Identifier: | NCT02787005 |
Other Study ID Numbers: |
3475-199 163366 ( Registry Identifier: JAPIC-CTI ) MK-3475-199 ( Other Identifier: Merck Protocol Number ) 2015-003644-40 ( EudraCT Number ) |
First Posted: | June 1, 2016 Key Record Dates |
Last Update Posted: | March 8, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: | http://engagezone.msd.com/ds_documentation.php |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
PD1 PD-1 PDL1 PD-L1 |
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms |
Prostatic Diseases Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents |