We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02787005




Registration number
NCT02787005
Ethics application status
Date submitted
26/05/2016
Date registered
26/05/2016
Date last updated
24/07/2018

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
2015-003644-40
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:
Metastatic Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Enzalutamide

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 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.

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.


Other interventions: Pembrolizumab
Intravenous infusion

Treatment: Drugs: Enzalutamide
Oral capsules

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
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 assessed by central imaging vendor (Cohorts 1 and 2 combined, Cohort 1, Cohort 2 and Cohort 4)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [1] 0 0
Disease Control Rate (DCR) (Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined, and by each cohort)
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Percentage of participants who experience an adverse event (AE) (All cohorts combined and by each cohort)
Timepoint [3] 0 0
Up to 27 months
Secondary outcome [4] 0 0
Percentage of participants who discontinue study drug due to an AE (All cohorts combined and by each cohort)
Timepoint [4] 0 0
Up to 2 years

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

- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
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.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Merck Sharp & Dohme - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Louisiana
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Dakota
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
South Dakota
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Germany
State/province [16] 0 0
Haar
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Hong Kong
Country [18] 0 0
Ireland
State/province [18] 0 0
Dublin
Country [19] 0 0
Japan
State/province [19] 0 0
Chiyoda-Ku, Tokyo
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Netherlands
State/province [21] 0 0
Haarlem
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Switzerland
State/province [23] 0 0
Lucerne 6
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Hoddesdon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
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/show/NCT02787005
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

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