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Study of Pembrolizumab (MK-3475) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)(MK-3475-199/KEYNOTE-199)

This study is currently recruiting participants.
Verified September 2017 by Merck Sharp & Dohme Corp.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02787005
First Posted: June 1, 2016
Last Update Posted: September 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC). Participants will be enrolled into one of five cohorts: Cohort 1 (participants with programmed cell death ligand 1 [PD-L1]-positive, measurable disease), Cohort 2 (participants with PD-L1 negative, measurable disease), Cohort 3 (participants with bone-metastases and non-measurable disease) post-chemotherapy, Cohort 4 (participants with Response Evaluation Criteria in Solid Tumors version 1.1- [RECIST 1.1]-measureable disease) and Cohort 5 (participants with bone metastases only or bone-predominant disease) pre-chemotherapy.

Condition Intervention Phase
Metastatic Castration-resistant Prostate Cancer Biological: Pembrolizumab Drug: Enzalutamide Phase 2

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 370
Actual Study Start Date: July 1, 2016
Estimated Study Completion Date: March 16, 2020
Estimated Primary Completion Date: December 3, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
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.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
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.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
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.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
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.
Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Enzalutamide
Oral capsules
Other Name: XTANDI®

Detailed Description:
Participants with mCRPC previously treated with docetaxel-based chemotherapy in Cohorts 1 to 3 will receive monotherapy with pembrolizumab. Chemotherapy-naïve subjects with mCRPC either having failed or showing signs of failure with enzalutamide in Cohorts 4 and 5 will receive pembrolizumab monotherapy in addition to their current regimen of enzalutamide. In all cohorts, pembrolizumab administration will occur on Day 1 of each 3-week dosing cycle and will continue for a maximum of 35 cycles (approximately 2 years) unless specific withdrawal/discontinuation criteria are met. Participants who discontinue after 35 infusions of pembrolizumab for reasons other than disease progression or intolerability, or who discontinue after attaining a complete response may be eligible for up to 17 additional infusions (approximately 1 year) after they have experienced disease progression.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 either a newly obtained biopsy or an archival specimen from a site not previously irradiated. Participants in Cohorts 1 and 2 with visceral/measurable lesions must provide a newly obtained biopsy performed after the last line of systemic therapy and an archival specimen, if available. Participants in Cohort 3 must 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 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.

For Cohorts 1, 2, 3, 4, and 5:

  • 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
  • Males of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.
  • Demonstrates adequate organ function.

Exclusion Criteria:

For Cohorts 1, 2, 3, 4, and 5:

  • 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.

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 signs of failure on enzalutamide treatment that would require imminent discontinuation of enzalutamide treatment.
  Contacts and Locations
Information from the National Library of Medicine

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


Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 37 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02787005     History of Changes
Other Study ID Numbers: 3475-199
2015-003644-40 ( EudraCT Number )
163366 ( Registry Identifier: JAPIC-CTI )
First Submitted: May 26, 2016
First Posted: June 1, 2016
Last Update Posted: September 22, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Pembrolizumab
Antineoplastic Agents