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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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)
Scientific title
Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199)
Secondary ID [1] 0 0
163366
Secondary ID [2] 0 0
3475-199
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to ~52 months
Secondary outcome [1] 0 0
Percentage of Participants Who Experienced an Adverse Event (AE)
Timepoint [1] 0 0
Up to ~52 months
Secondary outcome [2] 0 0
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [2] 0 0
Up to ~52 months
Secondary outcome [3] 0 0
Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
Timepoint [3] 0 0
Up to ~52 months
Secondary outcome [4] 0 0
Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
Timepoint [4] 0 0
Up to ~52 months
Secondary outcome [5] 0 0
DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
Timepoint [5] 0 0
Up to ~52 months
Secondary outcome [6] 0 0
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)
Timepoint [6] 0 0
Up to ~52 months
Secondary outcome [7] 0 0
Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined)
Timepoint [7] 0 0
Up to ~52 months
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
Up to ~52 months
Secondary outcome [9] 0 0
Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
Timepoint [9] 0 0
Up to ~52 months
Secondary outcome [10] 0 0
Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined)
Timepoint [10] 0 0
Up to ~52 months
Secondary outcome [11] 0 0
Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined)
Timepoint [11] 0 0
Up to ~52 months
Secondary outcome [12] 0 0
Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined)
Timepoint [12] 0 0
Up to ~52 months
Secondary outcome [13] 0 0
Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined)
Timepoint [13] 0 0
Up to ~52 months

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2022
Sample size
Target
Accrual to date
Final
388
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT02787005
Trial related presentations / publications
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

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02787005