Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 20.0Level: LLTClassification code: 10036910Term: Prostate cancer NOS Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506987-15-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Male
- Target Recruitment
- 1200
For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology, For Cohort B: Has received prior treatment with either abiraterone acetate or enzalutamide (but not both) in the prechemotherapy mCRPC state. Participants in Cohort B must have received at least 4 weeks of either abiraterone or enzalutamide treatment (but not both) who failed treatment or became intolerant of the drug, For Cohort C: Has received prior treatment with abiraterone acetate in the pre-chemotherapy mCRPC state without prior enzalutamide. Participants in Cohort C must have received at least 4 weeks of abiraterone treatment who failed treatment or become intolerant of the drug. Participants who received abiraterone acetate in the hormone-sensitive state will not be eligible, For Cohort D: Has not received chemotherapy for mCRPC and has either not had prior second generation hormonal manipulation for mCRPC OR has previously been treated with enzalutamide for mCRPC and failed treatment or has become intolerant of the drug. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if =4 weeks have elapsed from the last dose of docetaxel. Prior treatment with abiraterone acetate in the hormone-sensitive metastatic setting is allowed as long as there was no progression on this agent and abiraterone acetate was not discontinued due to adverse events (AEs), For Cohorts E, G and J: Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide or other next-generation hormonal agents [NHA]) are allowed. Participants who received prior ketoconazole for metastatic disease may be enrolled. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy. Prior docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC) is allowed if =4 weeks have elapsed from the last dose of docetaxel prior to Day 1 of Cycle 1, For Cohort F, H, and I: Participants must have received prior treatment with androgen deprivation therapy (ADT) for metastatic disease. Prior treatment with up to a total of 2 chemotherapies for mCRPC is allowed, as well as up to 2 second-generation hormonal manipulations for mCRPC. Participants who received prior ketoconazole for metastatic disease may be enrolled. Docetaxel for mHSPC is allowed in addition to docetaxel for mCRPC. If docetaxel chemotherapy is used more than once (eg, once for metastatic hormone-sensitive and once for mCRPC), it will be considered as 1 therapy, For Cohorts F, H, I: Has t-NE or de novo metastatic prostate cancer defined by =1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment. Epstein criteria of neuroendocrine differentiation in prostate cancer is used for eligibility. Specimens must have one of the morphologies of Small cell carcinoma or Large cell neuroendocrine carcinoma (LCNEC) or Mixed (small or large cell) NE carcinoma – acinar adenocarcinoma with positive IHC confirmed by central pathology review, Is able to provide tumor tissue from a site not previously irradiated as follows: Cohorts A, E, G and J: must provide a core or excisional biopsy fro
Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to first dose study therapy or who has not recovered (i.e., Grade =1 or at baseline) from AEs due to mAbs administered >4 weeks earlier, Has known active Hepatitis B or Hepatitis C, Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study therapy, Has known active central nervous system metastases and/or carcinomatous meningitis, Has a superscan” bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated, Has had prior solid, organ or bone marrow transplant, For Cohort A: Has experienced a seizure or seizures within 6 months of study start or is currently being treated with cytochrome P450 enzyme (CYP) inducing anti-epileptic drugs for seizures, For Cohort A: Is currently receiving strong or moderate inhibitors of CYP3A4 including azole antifungals; macrolide antibiotics; or protease inhibitors, For Cohort A: Is currently receiving strong or moderate inducers of CYP3A4, For Cohort A: Has myelodysplastic syndrome, For Cohort A: Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, or uncontrolled hypertension, Has had prior chemotherapy, targeted small molecule therapy abiraterone treatment, enzalutamide treatment, or radiation therapy within 2 weeks prior to first dose of study therapy or who has not recovered (ie, Grade =1 or at baseline) from AEs due to a previously administered agent, For Cohort B: Has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer, For Cohort B: Has peripheral neuropathy Common Terminology Criteria for Adverse Events =2 except due to trauma, For Cohort B: Has ascites and/or clinically significant pleural effusion, For Cohort B:Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), For Cohort B: Is currently receiving any of the following classes of inhibitors of CYP3A4: azole antifungals; macrolide antibiotics; or protease inhibitors, For Cohort C: Has received prior chemotherapy for mCRPC. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if =4 weeks elapsed from last dose of docetaxel. Participants who received abiraterone acetate in the hormone-sensitive state will not be eligible, For Cohort C: Has a history of seizure or any condition that may predispose to seizure (including, but not limited to prior cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation; or intracranial masses such as a schwannoma or meningioma that is causing edema or mass effect), For Cohort C:Has known or suspected brain metastasis or leptomeningeal carcinomatosis, For Cohort C: Has a history of loss of consciousness within 12 months of the screening visit, For Cohort C: Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit, Is currently participating in and receiving study therapy or has participated in a study of an investigational agent and received study drug or used an investigational device within 4 weeks of treatment allocation/randomization, For Cohort C: Has received treatm
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method