Phase II Trial of Pembrolizumab (MK-3475) in Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199)

Phase 2

Completed

Conditions: Prostate cancer
10038597

Registration Number: NL-OMON55373

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial. The
subject may also provide consent for Future Biomedical Research. However, the
subject may participate in the main trial without participating in Future
Biomedical Research.
2. Be *18 years of age on day of signing informed consent.
3. Have histologically- or cytologically-confirmed adenocarcinoma of the
prostate without small cell histology. Diagnosis must be stated in a pathology
report and confirmed by the Investigator.
4. Have RECIST 1.1-measurable prostate cancer on computed tomography (CT) or
magnetic resonance imaging (MRI) scans (Cohorts 1, 2 and 4) or detectable bone
metastases by whole body bone scintigraphy and no RECIST 1.1-measurable tumors
(Cohorts 3 and 5), as determined by central review. Disease must be either
metastatic or locally confined inoperable disease that cannot be treated with
definitive intent.
5. Have supplied tumor tissue from a newly obtained biopsy or provided a tumor
tissue specimen *12 months prior to the screening date and an archival
specimen, if available, from a site not previously irradiated (tumors
progressing in a prior site of radiation are allowed for PD-L1
characterization; other exceptions may be considered after Sponsor
consultation). Adequacy of these specimens for PD-L1 biomarker analysis will be
required by a central laboratory prior to enrollment. Subjects in Cohorts 1, 2
and 4 with visceral / measurable lesions must provide a newly obtained biopsy
performed after the last line of systemic therapy where safely available or a
specimen obtained *12 months prior to the screening date and an archival
specimen, if available. Subjects in Cohort 3 and 5 must at least provide an
archival specimen.
For Cohorts 1, 2, and 3 only:
6. Have been treated with:
a. At least one 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).
b. At least one regimen / line of chemotherapy that contained docetaxel.
c. No more than two chemotherapy regimens.
d. No more than three regimens / lines of the aforementioned treatments (having
failed / progressed on chemotherapy and targeted endocrine therapy).
For Cohorts 4 and 5 only:
7. For chemotherapy-naive subjects with mCRPC either having failed or showing
early signs of failing on enzalutamide treatment as defined by PCWG3-
guidelines (eg, signs of clinical progression, increased alkaline phosphatase,
PSA increase, or positive imaging assessments). Subjects can have failed prior
abiraterone treatment before current enzalutamide treatment. Subjects 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.
All Cohorts:
8. Have documented prostate cancer progression within 6 months prior to
screening, as determined by the Investigator, by means of one of the following:
a. 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.
b. Radiographic disease progression in soft tissu

Exclusion Criteria

1. 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 trial treatment.
2. 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 trial treatment. The use of physiologic doses of corticosteroids may be
approved after consultation with the Sponsor (replacement therapy for adrenal
insufficiency is permitted).
3. Has had a prior anti-cancer mAb within 4 weeks prior to the first dose of
trial treatment or who has not recovered (i.e., * Grade 1 or at baseline) from
AEs due to mAbs administered more than 4 weeks earlier.
4. Has had prior chemotherapy, targeted small molecule therapy, or external
beam radiation therapy within 4 weeks prior to the first dose of trial
treatment or who has not recovered (i.e., * Grade 1 or at baseline) from AEs
due to a previously administered agent. Treatment with Radium-223 is allowed as
long as the last dose has been administered no less than 4 weeks prior to the
first dose.
5. 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 or in situ cervical cancer.
6. Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they are stable (without evidence of progression by
imaging for at least 4 weeks prior to the first dose of trial treatment and any
neurologic symptoms have returned to baseline), have no evidence of new or
enlarging brain metastases, and are not using steroids for at least 7 days
prior to the first dose of trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
7. 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). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
8. Has evidence of interstitial lung disease and / or a history of
(non-infectious) pneumonitis that required steroids, or current pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject*s participation for the full duration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the treating
Investigator.
11. Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
12. Has previously participated in any other pembrolizumab (MK-3475) trial, or
received prior therapy with an anti-PD-1, anti-PD-L1, and anti-PD-L2 (including
ipilimumab or any other antibody or drug specifically targeting T-cell <b

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Cohorts 1, 2, and 4 - Objective Response Rate (ORR) - per RECIST 1.1 assessed<br /><br>by central imaging vendor: Proportion of subjects int he analysis population<br /><br>who have complete response (CR) or partial response (PR) where responses are<br /><br>determined by RECIST 1.1 assessed by central imaging vendor. </p><br>

Secondary Outcome Measures