Clinical Trials /

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

NCT02787005

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Study of Pembrolizumab (MK-3475) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Previously Treated With Chemotherapy (MK-3475-199/KEYNOTE-199)
  • Official Title:Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Previously Treated With Chemotherapy (KEYNOTE-199)

Clinical Trial IDs

  • ORG STUDY ID: 3475-199
  • SECONDARY ID: 2015-003644-40
  • NCT ID: NCT02787005

Trial Conditions

  • Metastatic Castration-resistant Prostate Cancer (mCRPC)

Trial Interventions

DrugSynonymsArms

Trial Purpose

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel-based chemotherapy. Participants will be enrolled into one of three cohorts: Cohort 1 (participants with programmed cell death ligand 1 [PD-L1]-positive, measurable disease), Cohort 2 (participants with PD-L1 negative, measurable disease), or Cohort 3 (participants with bone-metastases and non-measurable disease).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: PD-L1 positive with measurable diseaseExperimentalParticipants receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.
    Cohort 2: PD-L1 negative with measurable diseaseExperimentalParticipants receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.
      Cohort 3: Bone-metastases with non-measurable diseaseExperimentalParticipants receive pembrolizumab 200 mg via intravenous infusion on Day 1 of every 3-week cycle for up to 2 years.

        Eligibility 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 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.

        - 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 (chemotherapy and targeted endocrine therapy).

        - 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 serum testosterone <50 ng/dL (<2.0 nM).

        - Participants receiving bone resorptive therapy (including but 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:

        - 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 adverse events due to mAbs administered more than 4 weeks earlier.

        - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events 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, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

        - 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.

        - 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.

        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:Male
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by central imaging vendor (Cohorts 1 and 2 only)
        Time Frame:Up to 2 years
        Safety Issue:No
        Description:

        Secondary Outcome Measures

        Measure:Disease Control Rate (DCR) (All Cohorts)
        Time Frame:Up to 2 years
        Safety Issue:No
        Description:
        Measure:Prostate-specific Antigen (PSA) response rate (All Cohorts)
        Time Frame:Up to 2 years
        Safety Issue:No
        Description:
        Measure:Percentage of participants who experience an adverse event (AE)
        Time Frame:Up to 27 months
        Safety Issue:Yes
        Description:
        Measure:Percentage of participants who discontinue study drug due to an AE
        Time Frame:Up to 2 years
        Safety Issue:Yes
        Description:

        Trial Keywords

        • PD1
        • PD-1
        • PDL1
        • PD-L1