Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies inmCRPC (KEYNOTE-365)

Phase 1

• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); MedDRA version: 19.0Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002312-41-ES
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-08-17
• Last Update Posted: 30 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 210

Inclusion Criteria

1. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent 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 (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.
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.
Cohort A: A core or excisional biopsy from soft tissue or a bone biopsy is required. 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 newly obtained core or excisional biopsy from soft tissue is required.
Cohort C: 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.
5. 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 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.
Note: Radiographs must be collected and transmitted to the central imaging
vendor at study entry.
6. Have progression under the following conditions if the subject 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 (< 2.0 nM).
If the subject is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists (subjects who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to first dose of trial treatment and treatment must be continued throughout the study.
8. Subjects receiving bone resorptive therapy (including, but not limited to,
bisphosphonate or receptor activator of nuclear factor kappa-ß ligand inhibitor) must have been on stable doses for =4 weeks prior to first dose of trial treatment.
9. Agree to use an adequate method of contraception, if the subject is of reproductive potential, as outlined in Section 5

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.
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. 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
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 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 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 (e.g., 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 (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks prior to first dose of trial treatment
17. Has known active central nervous system metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate in
Cohorts A (pembrolizumab + olaparib) or B (pembrolizumab + docetaxel) provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to treatment allocation and any neurologic symptoms have returned to baseline), have

Study & Design

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