Phase II Trial of MK-3475 in Subjects with mCRPC with Prior Chemotherapy

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: EUCTR2015-003644-40-ES

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: 250

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 and 2) or detectable bone metastases by whole body bone scintigraphy and no RECIST 1.1-measurable tumors (Cohort 3), 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 either a newly obtained biopsy or an archival specimen 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 evaluated by a central laboratory prior to enrollment. Subjects in Cohorts 1 and 2 must provide a newly obtained biopsy performed after the last line of systemic therapy (required for at least the first 150 subjects screened and up to 300 subjects screened) and an archival specimen, if available. Subjects in Cohort 3 must provide an archival specimen.
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 (chemotherapy and targeted endocrine therapy).
7. 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 three 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 or bone with or without PSA progression
8. Have ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 2.0 nM). If the subject is currently being treated with LHRH agonists (subjects who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to first dose of trial treatment. This treatment must be continued throughout the study.
9. Subjects receiving bone resorptive therapy (including but limited to bisphosphonate or RANK-L inhibitor) must have been on stable doses for ? 4 weeks prior to first dose of trial treatment.
10. Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
11. Male subjects of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
12. Demonstrate adequate organ function as defined in protocol
Are the trial subjects under 18? no
Number of subjects for this age

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 monoclonal antibody (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 adverse events due to mAbs administered more than 4 weeks earlier.
4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ? Grade 1 or at baseline) from adverse events due to a previously administered agent.
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, 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 four 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.
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 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 (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
15. Has received a live vaccine within 30 days of planned start of study therapy.