Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer.

Phase 1

• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002312-41-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-15
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 1000

Inclusion Criteria

1. Be willing and able to provide documented informed consent/assent for the trial.
2. Be <=18 years of age on day of signing informed consent.
3. Histology:
a. For Cohorts A, B, C, D, E, G: Have histologically- or cytologically confirmed
(if acceptable according to local health authority regulations) adenocarcinoma of the prostate without small cell histology. Diagnosis must be stated in a pathology report and confirmed by the investigator.
b. For Cohorts F, H, I: Have t-NE prostate cancer defined by =1% neuroendocrine cells in a recent biopsy specimen from a metastasis as determined by the investigational site. Neuroendocrine diagnosis must then be confirmed by central histology review prior to enrollment. Subjects must have prior histologic evidence of adenocarcinoma of the prostate gland by investigator report.
4. For all Cohorts: Have provided tumor tissue from a site not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed; other exceptions may be considered after Sponsor consultation). Adequacy of these for biomarker analysis will be evaluated by a central laboratory prior to enrollment. Cohorts A, E, & G: A core or excisional biopsy from soft tissue or a bone biopsy is required. A biopsy from soft tissue is preferred. In lieu of a soft tissue biopsy, a fresh bone biopsy is permitted. This biopsy must be performed within 1 year of screening and after developing mCRPC. A recent prior archival specimen should also be provided for these
subjects, if available. Cohort B: An archival tumor tissue sample or tumor tissue from a fresh core or excisional biopsy from soft tissue is required. Cohorts C & D: Subjects with soft tissue disease must provide a core or excisional biopsy from a soft tissue lesion if clinically accessible. In addition to the biopsy an archival specimen should also be provided if one is available. The biopsy must be performed within 1 year of screening and after developing mCRPC. If soft tissue disease cannot be biopsied then an archival specimen is required. For subjects with bone metastasis only, an archival tumor tissue specimen must be provided. Cohorts F, H, & I (neuroendocrine cohorts): A core or excisional biopsy from soft tissue or a bone biopsy is required. A biopsy from soft tissue is preferred. In lieu of a soft tissue biopsy, a fresh bone biopsy is permitted. This biopsy must be performed within 1 year of screening after developing mCRPC and demonstrate neuroendocrine histology as defined above under histology. A recent prior archival specimen should also be provided for these subjects, if available.
5.Have prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following:
a. PSA progression using local laboratory values as defined by a minimum of 2 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 tissue based on RECIST 1.1 criteria with or without PSA progression.
c. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA
progression.

For more inclusion criteria please see the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for th

Exclusion Criteria

1. Has had a prior anticancer mAb within 4 weeks prior to first dose of trial treatment or who has not recovered (ie, Grade =1 or at baseline) from AEs due to mAbs administered more than 4 weeks prior to first dose of trial treatment.
2. Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study
therapy or used an investigational device within 4 weeks of the treatment allocation/randomization.
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days
prior to treatment allocation/randomization. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor (replacement therapy for adrenal insufficiency is permitted).
4. If a subject has undergone major surgery, they must have recovered adequately from the toxicities and/or complications from the intervention prior to starting therapy.
5. Has had a prior radium treatment or treatment with other therapeutic radiopharmaceuticals for prostate cancer.
6. 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 or squamous cell carcinoma of the skin that has undergone potentially curative therapy.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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 a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
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 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 co-stimulation or checkpoint pathways)
13. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
14. Has known active hepatitis B virus (eg, hepatitis B surface antigen reactive) or hepatitis C virus (HCV) (e.g., HCV RNA [qualitative] is
detected)
15. Has received a live vaccine within 30 days of the first dose of trial treatment
16. Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto, ginkgo, turmeric, red rice yeast, citrus pectin polysaccharide, dehydroepiandrosterone) within 4 weeks prior to treatment allocation/randomization.

Cohort specific exclusion criteria are to be found in the protocol

For more exclusion criteria please see the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified