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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002312-41-IE
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-05-20
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 1200

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 providing documented informed consent.
3. Histology:
a. For Cohorts A, B, C, D, E, G, J: Have histol.- or cytol.-confirmed 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 or de novo metastatic prostate cancer defined by =1% neuroendocrine cells that are in discrete regions of a recent biopsy specimen. Neuroendocrine histology must be confirmed by central histology review prior to enrollment. Participants with t-NE 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. Adequacy of these for biomarker analysis will be evaluated by a central laboratory prior to enrollment.
Cohorts A, E, G & J: 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 bone biopsy is permitted. Biopsies must have been performed within 1 year of screening and after developing mCRPC to be eligible for the study. Biopsies can be newly obtained biopsies or archival specimens.
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: Participants 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 participants with bone metastasis only, an archival tumor tissue specimen must be provided.
Cohorts F, H, & I: A core or excisional biopsy from soft tissue or a biopsy is required. A biopsy from soft tissue is preferred. In lieu of a soft tissue biopsy, a bone biopsy is permitted. Biopsies must have been performed within 1 year of screening and after developing mCRPC and demonstrate neuroendocrine histology as defined above under histology to be eligible for the study.
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.
6. Have progression under the following conditions if the participant received anti-androgen therapy prior to enrollment:
a. Evidence of progression >4 weeks since last flutamide treatment.
b. Evidence of progression >6 weeks since last bicalutamide or nilutamide treatment.
7. Have ongoing androgen deprivation with serum testosterone <50 ng/dL (< 1.7 nM).
If the participant is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists this therapy must have been initiated at least 4 weeks prior to first dose of trial tr

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 participant 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 prior treatment with therapeutic radiopharmaceuticals for prostate cancer, such as Radium-223 or Leutitium-177, within 4 weeks prior to the first dose of trial treatment.
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 (noninfectious) 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 participant's participation for the full duration of the trial, or is not in the best interest of the participant 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 costimulation 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 or live-attenuated vaccine within 30 days of the first dose of trial treatment.
Refer to Section 5.5.2 of study protocol for more information on COVID-19 vaccines
16. Has used herbal or medicinal products that may have hormonal antiprostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto, ginkgo, turmeric, red rice yeast, citrus pectin polysaccharide, dehydroepiandrosterone, megestrol) within 4 weeks prior to treatment allocation/randomization.
17. Has known active central nervou

Study & Design

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