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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02787005
Registration number
NCT02787005
Ethics application status
Date submitted
26/05/2016
Date registered
1/06/2016
Date last updated
24/03/2023
Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)(MK-3475-199/KEYNOTE-199)
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Scientific title
Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199)
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Secondary ID [1]
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163366
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Secondary ID [2]
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3475-199
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer
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Condition category
Condition code
Cancer
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Prostate
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Pembrolizumab
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.
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.
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.
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 for up to 2 years.
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 for up to 2 years.
Other interventions: Pembrolizumab
Intravenous infusion
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
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Assessment method [1]
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ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 by central imaging vendor. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, as well as in Cohorts 1, 2, and 4 separately for the first course of treatment.
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Timepoint [1]
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Up to ~52 months
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Secondary outcome [1]
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Percentage of Participants Who Experienced an Adverse Event (AE)
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Assessment method [1]
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An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants that experienced at least one AE for the first course of treatment was reported.
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Timepoint [1]
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Up to ~52 months
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Secondary outcome [2]
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Percentage of Participants Who Discontinued Study Treatment Due to an AE
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Assessment method [2]
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An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinued study treatment during the first course of treatment due to an AE was reported.
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Timepoint [2]
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Up to ~52 months
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Secondary outcome [3]
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Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
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Assessment method [3]
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Percentage of participants who had CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions)or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for at least 6 months, by central imaging vendor where progressive disease (PD) in bone-only tumors were determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3) criteria and PD for all other tumors was determined using RECIST 1.1. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
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Timepoint [3]
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Up to ~52 months
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Secondary outcome [4]
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Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
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Assessment method [4]
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DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; =30% decrease in the sum of diameters of target lesions) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3)-modified RECIST 1.1 criteria and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment.
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Timepoint [4]
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Up to ~52 months
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Secondary outcome [5]
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DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
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Assessment method [5]
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DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; =30% decrease in the sum of diameters of target lesions) ) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using RECIST 1.1 and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment.
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Timepoint [5]
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Up to ~52 months
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Secondary outcome [6]
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Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined)
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Assessment method [6]
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Percentage of participants who had PSA response defined as at least 50% decline from baseline measured twice at least 3 weeks apart. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 for the first course of treatment.
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Timepoint [6]
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Up to ~52 months
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Secondary outcome [7]
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Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined)
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Assessment method [7]
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Time to PSA progression was defined as the time from first day of study treatment to the date of PSA progression. Participants without PSA progression were censored at the last PSA assessment date. PSA progression was defined as the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir were documented. For participants who had a decline in PSA during treatment, PSA progression must have been confirmed by a second value 3 or more weeks later increased with respect to the nadir PSA. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
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Timepoint [7]
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Up to ~52 months
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Secondary outcome [8]
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Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined)
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Assessment method [8]
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rPFS was defined as the time from first day of study treatment to the documented disease progression by central imaging vendor where PD in bone-only tumors was determined by radionuclide bone scan using PCWG3 criteria and PD for all other tumors were determined using RECIST 1.1 or death due to any cause, whichever occurs first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
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Timepoint [8]
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Up to ~52 months
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Secondary outcome [9]
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Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
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Assessment method [9]
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OS was defined as the time from first day of study treatment to the time of death. Participants without documented death were censored at the date of the last follow up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
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Timepoint [9]
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Up to ~52 months
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Secondary outcome [10]
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Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined)
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Assessment method [10]
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Duration of PSA response was defined as the time from PSA response, when the PSA value first declined by at least 50% of the baseline (must have been confirmed by a second value), to the date of PSA progression at which there was an increase of 25% or more from the nadir PSA, provided the absolute increase from the nadir PSA was at least 2 ng/mL. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
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Timepoint [10]
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Up to ~52 months
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Secondary outcome [11]
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Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined)
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Assessment method [11]
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Time to initiation of cytotoxic chemotherapy was defined as the time from first day of study treatment to the time of initiation of cytotoxic chemotherapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
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Timepoint [11]
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Up to ~52 months
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Secondary outcome [12]
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Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined)
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Assessment method [12]
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Time to new-anticancer therapy was defined as the time from first day of study treatment to the time of new-anticancer therapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
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Timepoint [12]
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Up to ~52 months
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Secondary outcome [13]
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Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined)
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Assessment method [13]
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Time to initiation of first skeletal-related event was defined as the time from first day of study treatment to the first skeletal-related event, which was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change or antineoplastic therapy to treat bone pain. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
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Timepoint [13]
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Up to ~52 months
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Males
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Can healthy volunteers participate?
No
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Key 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 messenger ribonucleic
acid (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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/07/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
28/02/2022
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Sample size
Target
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Accrual to date
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Final
388
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Recruitment in Australia
Recruitment state(s)
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02787005
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02787005
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