Metastatic Castration-Resistant Prostate CancerPhase 1/2NCT02861573
Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)
A Phase 1/2 study testing Pembrolizumab 200 mg, Olaparib 400 mg and Docetaxel 75 mg/m^2 in people with Metastatic Castration-Resistant Prostate Cancer, run by Merck Sharp & Dohme LLC.
Trial summary
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration resistant prostate cancer (mCRPC). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-Resistant Prostate Cancer
- What is being tested?
- Pembrolizumab 200 mg, Olaparib 400 mg and Docetaxel 75 mg/m^2
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,200 participants
- Where
- No sites listed yet
- Study dates
- 17 Nov 2016to 24 Jul 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
- 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 from soft tissue or bone biopsy within 1 year of screening and after developing mCRPC; Cohort B: must provide an archival tumor tissue sample or tumor tissue from a newly obtained core or excisional biopsy from soft tissue if the lesion is clinically accessible; Cohorts C and D with soft tissue disease: must provide a core or excisional biopsy from a soft tissue lesion if clinically accessible within 1 year of screening and after developing mCRPC and an archival specimen if available; and Cohorts F, H, and I must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen
- Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: 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; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Treatment with luteinizing hormone-releasing hormone agonists or antagonists for all cohorts must have been initiated ≥4 weeks prior to first dose of study therapy and must be continued throughout the study. Participants with de novo metastatic NE prostate cancer will not be required to have been previously treated with androgen deprivation therapy (ADT). ADT must be started in these participants by the time of treatment allocation/randomization
- Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa-β ligand inhibitor) must be on stable doses for ≥4 weeks prior to first dose of study therapy
Show all 14Show fewer
- Must be abstinent from heterosexual intercourse, refrain from donating sperm, or agree to use contraception (unless confirmed to be azoospermic) during the intervention period starting with the first dose of study therapy. The length of time required to continue contraception after the last dose of study intervention for each study intervention is as follows: 7 days for abiraterone acetate and lenvatinib; 30 days for enzalutamide; and 95 days for olaparib, docetaxel, and carboplatin/etoposide. No contraception measures are required during and after the intervention period for pembrolizumab/vibostolimab coformulation
- Has a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale for Cohorts A and C and a performance status of 0 or 1 for Cohorts B, D, E, F, G, H, I and J within 10 days of study start
- For Cohort A: Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (e.g., abiraterone acetate and/or enzalutamide) are allowed. Prior docetaxel for metastatic hormone-sensitive prostate cancer is allowed if ≥4 weeks have elapsed from the last dose of docetaxel prior to day 1 of Cycle 1
- 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
Who cannot join
- 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 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
- 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
- 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
- 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
- Has an active autoimmune disease that has required systemic treatment in past 2 years
Show all 54Show fewer
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- Has previously participated in any other pembrolizumab trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 1 (anti-PD-L2)
- Has a known history of Human Immunodeficiency Virus (HIV)
- 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
- 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
- For Cohort C: Has received treatment with 5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogens, and/or cyproterone within 4 weeks prior to Cycle 1
- For Cohort C: Has a history of prostate cancer progression on ketoconazole
- For Cohort D: Has received prior treatment with docetaxel or another chemotherapy agent for metastatic prostate cancer
- For Cohort D: Has progressed on prior abiraterone acetate for treatment of castration sensitive or resistant metastatic prostate cancer
- For Cohort D: Has discontinued prior treatment with abiraterone acetate due to AEs
- For Cohort D: Has previously been treated with ketoconazole for prostate cancer for >7 days
- For Cohort D: Has received prior systemic treatment with an azole drug (eg, fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
- For Cohort D: Has uncontrolled hypertension (systolic BP ≥ 160 mm Hg or diastolic BP ≥ 95 mm Hg)
- For Cohort D: Has a history of pituitary or adrenal dysfunction
- For Cohort D: Has clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline
- For Cohort D: Has atrial fibrillation, or other cardiac arrhythmia requiring therapy
- For Cohort D: Has a history of chronic liver disease
- For Cohort D: Is currently receiving strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during abiraterone acetate treatment, CYP2D6 substrates with a narrow therapeutic index (for example thioridazine), or CYP2C8 substrates with a narrow therapeutic index (for example pioglitazone)
- For Cohorts E and F: Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
- For Cohorts E and F: Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
- For Cohorts E and F: Has prolongation of QT interval by Fredericia (QTcF) interval to >480 milliseconds
- For Cohorts E and F: Has had major surgery within 3 weeks prior to first dose of study interventions
- For Cohorts E and F: Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
- For Cohorts E and F: Has had significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of New York Heart Association >Class II congestive heart failure, unstable angina, myocardial infarction, or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability
- For Cohorts E and F: Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of lenvatinib
- For Cohorts E and F: Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib
- For Cohorts G, H, and I: Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody
- For Cohorts G, H, and I: Has symptomatic ascites or pleural effusion
- For Cohort I: Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
- For Cohort I: Has received previous treatment for prostate cancer with platinum-containing compounds
About this study
Official title: Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365)
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration resistant prostate cancer (mCRPC). There will be ten cohorts in this study: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, Cohort C will receive pembrolizumab + enzalutamide, Cohort D will receive pembrolizumab + abiraterone + prednisone Cohort E will receive pembrolizumab+lenvatinib, Cohort F will receive pembrolizumab+lenvatinib, Cohort G will receive pembrolizumab/vibostolimab coformulation (MK-7684A), Cohort H will receive pembrolizumab/vibostolimab coformulation, Cohort I will receive pembrolizumab+carboplatin+etoposide in Arm 1 and carboplatin+etoposide in Arm 2 and Cohort J will receive belzutifan in Arm1 and Pembrolizumab+belzutifan in Arm 2. Outcome measures will be assessed individually for each cohort.
Read the detailed description
Assignment of patients to a cohort will be based on prior treatment as outlined in the eligibility criteria.
Participants who discontinue pembrolizumab or vibostolimab+pembrolizumab after 35 infusions for reasons other than disease progression or intolerability, or who discontinue pembrolizumab or coformulation of pembrolizumab/vibostolimab after attaining a complete response (and had at least 8 administrations of pembrolizumab or pembrolizumab/vibostolimab coformulation and at least 2 treatments with pembrolizumab or pembrolizumab/vibostolimab coformulation beyond initial complete response) may be eligible to receive a second course of treatment that includes up to 17 additional infusions (approximately 1 year) of pembrolizumab monotherapy or pembrolizumab/vibostolimab coformulation after they have experienced radiographic disease progression after stopping first course treatment.
Effective with Protocol Amendment 08, enrollment into Cohorts A, B, C, and D was closed.
Effective with Protocol Amendment 14, enrollment into Cohorts E, F, G, and H was closed (not due to any safety issues). No further efficacy and survival follow-up assessments will be collected in Cohorts A through H.
Effective with Protocol Amendment 16, enrollment into Cohort J was closed (not due to any safety issues).
- Being tested
- Pembrolizumab 200 mg, Olaparib 400 mg, Docetaxel 75 mg/m^2, Prednisone 5 mg, Enzalutamide 160 mg
- Keywords
- Metastatic Castration-Resistant Prostate Cancer, mCRPC, PD1, PD-1, PDL1, PD-L1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab 200 mgBiological
Also called KEYTRUDA®, MK-3475
IV Q3W
Olaparib 400 mgDrug
Also called LYNPARZA®, MK-7339
Eight 50-mg capsules PO BID
Docetaxel 75 mg/m^2Drug
Also called TAXOTERE®
IV Q3W
Prednisone 5 mgDrug
One 5-mg tablet PO BID
Enzalutamide 160 mgDrug
Also called XTANDI®
Four 40-mg capsules, four 40-mg tablets, or two 80-mg tablets PO QD
Dexamethasone 8 mgOther
Premedication for Cohort B given PO at 12, 3, and 1 hours prior to docetaxel infusion Q3W
Olaparib 300 mgDrug
Also called LYNPARZA®, MK-7339
Two 150-mg tablets PO BID
Abiraterone acetate 1000 mgDrug
Also called ZYTIGA®
Two 500-mg or four 250-mg tablets PO QD
LenvatinibDrug
Also called LENVIMA®, MK-7902
20 mg PO QD
Pembrolizumab/Vibostolimab coformulationBiological
Also called MK-7684A
IV Q3W
CarboplatinDrug
Also called PARAPLATIN®
IV Q3W
EtoposideDrug
Also called TOPOSAR™
IV on Days 1, 2 and 3 of each cycle
Belzutifan 120mgBiological
Also called WELIREG™
PO QD
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab+Olaparib | Experimental | Participants with adenocarcinoma (AC) mCRPC in Cohort A will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Olaparib 400 mg; Drug: Olaparib 300 mg |
| Pembrolizumab+Docetaxel+Prednisone | Experimental | Participants with AC mCRPC in Cohort B will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel 75 mg/m^2 IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Docetaxel 75 mg/m^2; Drug: Prednisone 5 mg; Other: Dexamethasone 8 mg |
| Pembrolizumab+Enzalutamide | Experimental | Participants with AC mCRPC in Cohort C will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Enzalutamide 160 mg |
| Pembrolizumab+Abiraterone+Prednisone | Experimental | Participants with AC mCRPC in Cohort D will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Prednisone 5 mg; Drug: Abiraterone acetate 1000 mg |
| Pembrolizumab+Lenvatinib: AC | Experimental | Participants with AC mCRPC in Cohort E will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Lenvatinib |
| Pembrolizumab+Lenvatinib:t-NE | Experimental | Participants with neuroendocrine (t-NE) mCRPC in Cohort F will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Receives: Biological: Pembrolizumab 200 mg; Drug: Lenvatinib |
| Pembrolizumab/Vibostolimab coformulation | Experimental | Participants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Receives: Biological: Pembrolizumab/Vibostolimab coformulation |
| Pembrolizumab/Vibostolimab coformulation:t-NE | Experimental | Participants with t-NE mCRPC in Cohort H will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Receives: Biological: Pembrolizumab/Vibostolimab coformulation |
| Pembrolizumab+Carboplatin+Etoposide | Experimental | Participants with neuroendocrine mCRPC in Cohort I Arm 1 will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs. Receives: Biological: Pembrolizumab 200 mg; Drug: Carboplatin; Drug: Etoposide |
| Carboplatin+Etoposide | Experimental | Participants with neuroendocrine mCRPC in Cohort I Arm 2 will receive carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. Receives: Drug: Carboplatin; Drug: Etoposide |
| Belzutifan | Experimental | Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Receives: Biological: Belzutifan 120mg |
| Pembrolizumab+Belzutifan | Experimental | Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Receives: Biological: Pembrolizumab 200 mg; Biological: Belzutifan 120mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Decrease of ≥50% in Prostatic Specific Antigen (PSA)
Measured: From Baseline Measured Every 3 Weeks Until Radiographic Progression Estimated to be Approximately 2 Years
Number of Participants with Adverse Events (AEs)
Measured: Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Number of Participants Discontinuing Study Drug Due to AEs
Measured: Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Secondary outcomes (7)
Disease Control Rate (DCR) Based on Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 Assessed by BICR
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Overall Survival (OS)
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Duration of Response (DOR) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
ORR Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Time to PSA Progression
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Radiographic Progression-free Survival (rPFS) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Composite Response Rate Defined as Any One of the Following: A. Response Based on RECIST 1.1; B. PSA Decrease of ≥50%; or C. Circulating Tumor-cell Count Conversion (Pembrolizumab + Olaparib Cohort Only)
Measured: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2016 (estimated)
- Study start17 Nov 2016
- Primary completion22 Oct 2027 (estimated)
- Study completion24 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metastatic Castration-Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02861573
- Sponsor's protocol ID
- 3475-365
- Other IDs
- KEYNOTE-365, MK-3475-365, 2023-506987-15-00, U1111-1294-7577, 2016-002312-41, 2016, 2023
- Status last verified
- Jul 2026
- First submitted
- 3 Aug 2016
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Yu EY, Ferrario C, Linch MD, Stoeckle M, Laguerre B, Arranz JA, Todenhofer T, Fong PC, Piulats JM, Berry W, Emmenegger U, Mourey L, Joshua AM, Mar N, Appleman LJ, Conter HJ, Gravis G, Li XT, Schloss C, Poehlein C, de Bono JS. Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D. Eur Urol Oncol. 2025 Jun;8(3):641-651. doi: 10.1016/j.euo.2024.05.013. Epub 2024 Jun 25.
PubMed 38926066Yu EY, Berry WR, Gurney H, Retz M, Conter HJ, Laguerre B, Fong PCC, Ferrario C, Todenhofer T, Gravis G, Piulats JM, Emmenegger U, Shore ND, Romano E, Mourey L, Li XT, Poehlein CH, Schloss C, Appleman LJ, de Bono JS. Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study. Eur Urol Oncol. 2024 Jun;7(3):509-518. doi: 10.1016/j.euo.2023.10.008. Epub 2023 Nov 7.
PubMed 37940446Augustin M, Laguerre B, Baldini C, Zedan AH, Gonzalez-Billalabeitia E, Fong PC, Zukov R, Hammerer P, Prentice M, Shore N, Necchi A, Todenhofer T, Kessler ER, Kose F, Gurney H, Valderrama BP, Zhu P, Imai K, Liu Y, McDermott R. Pembrolizumab Plus Lenvatinib in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort E. Eur Urol Oncol. 2026 May 2:S2588-9311(26)00084-2. doi: 10.1016/j.euo.2026.03.026. Online ahead of print.
PubMed 42070919Fong PC, Kwiatkowski M, Mosca A, Valderrama BP, Li C, Huang YH, Zedan AH, Kuc K, Wiechno P, Laguerre B, Gonzalez-Billalabeitia E, Osipov M, Sener Dede D, Goh JC, Daugaard G, Zhu P, Imai K, Liu Y, Arranz Arija JA. Vibostolimab Coformulated with Pembrolizumab in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: KEYNOTE-365 Cohort G. Eur Urol Focus. 2026 Mar;12(2):168-173. doi: 10.1016/j.euf.2025.07.018. Epub 2025 Aug 11.
PubMed 40796417Yu EY, Kolinsky MP, Berry WR, Retz M, Mourey L, Piulats JM, Appleman LJ, Romano E, Gravis G, Gurney H, Bogemann M, Emmenegger U, Joshua AM, Linch M, Sridhar S, Conter HJ, Laguerre B, Massard C, Li XT, Schloss C, Poehlein CH, de Bono JS. Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study. Eur Urol. 2022 Jul;82(1):22-30. doi: 10.1016/j.eururo.2022.02.023. Epub 2022 Apr 6.
PubMed 35397952
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365)
- ClinicalTrials.gov ID
- NCT02861573
- Acronym / sponsor ID
- 3475-365
- Keywords
- Metastatic Castration-Resistant Prostate Cancer, mCRPC, PD1, PD-1, PDL1, PD-L1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2016 (actual)
- Primary completion
- 22 Oct 2027 (estimated)
- Study completion
- 24 Jul 2028 (estimated)
- First posted
- 10 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration resistant prostate cancer (mCRPC). There will be ten cohorts in this study: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, Cohort C will receive pembrolizumab + enzalutamide, Cohort D will receive pembrolizumab + abiraterone + prednisone Cohort E will receive pembrolizumab+lenvatinib, Cohort F will receive pembrolizumab+lenvatinib, Cohort G will receive pembrolizumab/vibostolimab coformulation (MK-7684A), Cohort H will receive pembrolizumab/vibostolimab coformulation, Cohort I will receive pembrolizumab+carboplatin+etoposide in Arm 1 and carboplatin+etoposide in Arm 2 and Cohort J will receive belzutifan in Arm1 and Pembrolizumab+belzutifan in Arm 2. Outcome measures will be assessed individually for each cohort.
Detailed description
Assignment of patients to a cohort will be based on prior treatment as outlined in the eligibility criteria.
Participants who discontinue pembrolizumab or vibostolimab+pembrolizumab after 35 infusions for reasons other than disease progression or intolerability, or who discontinue pembrolizumab or coformulation of pembrolizumab/vibostolimab after attaining a complete response (and had at least 8 administrations of pembrolizumab or pembrolizumab/vibostolimab coformulation and at least 2 treatments with pembrolizumab or pembrolizumab/vibostolimab coformulation beyond initial complete response) may be eligible to receive a second course of treatment that includes up to 17 additional infusions (approximately 1 year) of pembrolizumab monotherapy or pembrolizumab/vibostolimab coformulation after they have experienced radiographic disease progression after stopping first course treatment.
Effective with Protocol Amendment 08, enrollment into Cohorts A, B, C, and D was closed.
Effective with Protocol Amendment 14, enrollment into Cohorts E, F, G, and H was closed (not due to any safety issues). No further efficacy and survival follow-up assessments will be collected in Cohorts A through H.
Effective with Protocol Amendment 16, enrollment into Cohort J was closed (not due to any safety issues).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab+Olaparib | Experimental | Biological: Pembrolizumab 200 mg, Drug: Olaparib 400 mg, Drug: Olaparib 300 mgParticipants with adenocarcinoma (AC) mCRPC in Cohort A will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. |
| Pembrolizumab+Docetaxel+Prednisone | Experimental | Biological: Pembrolizumab 200 mg, Drug: Docetaxel 75 mg/m^2, Drug: Prednisone 5 mg, Other: Dexamethasone 8 mgParticipants with AC mCRPC in Cohort B will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel 75 mg/m^2 IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. |
| Pembrolizumab+Enzalutamide | Experimental | Biological: Pembrolizumab 200 mg, Drug: Enzalutamide 160 mgParticipants with AC mCRPC in Cohort C will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug. |
| Pembrolizumab+Abiraterone+Prednisone | Experimental | Biological: Pembrolizumab 200 mg, Drug: Prednisone 5 mg, Drug: Abiraterone acetate 1000 mgParticipants with AC mCRPC in Cohort D will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. |
| Pembrolizumab+Lenvatinib: AC | Experimental | Biological: Pembrolizumab 200 mg, Drug: LenvatinibParticipants with AC mCRPC in Cohort E will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. |
| Pembrolizumab+Lenvatinib:t-NE | Experimental | Biological: Pembrolizumab 200 mg, Drug: LenvatinibParticipants with neuroendocrine (t-NE) mCRPC in Cohort F will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. |
| Pembrolizumab/Vibostolimab coformulation | Experimental | Biological: Pembrolizumab/Vibostolimab coformulationParticipants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. |
| Pembrolizumab/Vibostolimab coformulation:t-NE | Experimental | Biological: Pembrolizumab/Vibostolimab coformulationParticipants with t-NE mCRPC in Cohort H will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. |
| Pembrolizumab+Carboplatin+Etoposide | Experimental | Biological: Pembrolizumab 200 mg, Drug: Carboplatin, Drug: EtoposideParticipants with neuroendocrine mCRPC in Cohort I Arm 1 will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs. |
| Carboplatin+Etoposide | Experimental | Drug: Carboplatin, Drug: EtoposideParticipants with neuroendocrine mCRPC in Cohort I Arm 2 will receive carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 Q3W + etoposide 100 mg/m^2 IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug. |
| Belzutifan | Experimental | Biological: Belzutifan 120mgParticipants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. |
| Pembrolizumab+Belzutifan | Experimental | Biological: Pembrolizumab 200 mg, Biological: Belzutifan 120mgParticipants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- For Cohorts A, B, C, D, E, G, J: Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
- 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 from soft tissue or bone biopsy within 1 year of screening and after developing mCRPC; Cohort B: must provide an archival tumor tissue sample or tumor tissue from a newly obtained core or excisional biopsy from soft tissue if the lesion is clinically accessible; Cohorts C and D with soft tissue disease: must provide a core or excisional biopsy from a soft tissue lesion if clinically accessible within 1 year of screening and after developing mCRPC and an archival specimen if available; and Cohorts F, H, and I must provide a core or excisional biopsy from soft tissue or a bone biopsy. For de novo metastatic neuroendocrine prostate participants, biopsies must be performed within 1 year of screening. Participants with bone metastasis only must provide an archival tumor tissue specimen
- Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: 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; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months
- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Treatment with luteinizing hormone-releasing hormone agonists or antagonists for all cohorts must have been initiated ≥4 weeks prior to first dose of study therapy and must be continued throughout the study. Participants with de novo metastatic NE prostate cancer will not be required to have been previously treated with androgen deprivation therapy (ADT). ADT must be started in these participants by the time of treatment allocation/randomization
- Participants receiving bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa-β ligand inhibitor) must be on stable doses for ≥4 weeks prior to first dose of study therapy
Key exclusion criteria (54 listed)
- 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 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
- 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
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab 200 mgAlso: KEYTRUDA®, MK-3475IV Q3W | Biological | Pembrolizumab+Abiraterone+Prednisone, Pembrolizumab+Belzutifan, Pembrolizumab+Carboplatin+Etoposide, Pembrolizumab+Docetaxel+Prednisone, Pembrolizumab+Enzalutamide, Pembrolizumab+Lenvatinib: AC, Pembrolizumab+Lenvatinib:t-NE, Pembrolizumab+Olaparib |
| Olaparib 400 mgAlso: LYNPARZA®, MK-7339Eight 50-mg capsules PO BID | Drug | Pembrolizumab+Olaparib |
| Docetaxel 75 mg/m^2Also: TAXOTERE®IV Q3W | Drug | Pembrolizumab+Docetaxel+Prednisone |
| Prednisone 5 mgOne 5-mg tablet PO BID | Drug | Pembrolizumab+Abiraterone+Prednisone, Pembrolizumab+Docetaxel+Prednisone |
| Enzalutamide 160 mgAlso: XTANDI®Four 40-mg capsules, four 40-mg tablets, or two 80-mg tablets PO QD | Drug | Pembrolizumab+Enzalutamide |
| Dexamethasone 8 mgPremedication for Cohort B given PO at 12, 3, and 1 hours prior to docetaxel infusion Q3W | Other | Pembrolizumab+Docetaxel+Prednisone |
| Olaparib 300 mgAlso: LYNPARZA®, MK-7339Two 150-mg tablets PO BID | Drug | Pembrolizumab+Olaparib |
| Abiraterone acetate 1000 mgAlso: ZYTIGA®Two 500-mg or four 250-mg tablets PO QD | Drug | Pembrolizumab+Abiraterone+Prednisone |
| LenvatinibAlso: LENVIMA®, MK-790220 mg PO QD | Drug | Pembrolizumab+Lenvatinib: AC, Pembrolizumab+Lenvatinib:t-NE |
| Pembrolizumab/Vibostolimab coformulationAlso: MK-7684AIV Q3W | Biological | Pembrolizumab/Vibostolimab coformulation, Pembrolizumab/Vibostolimab coformulation:t-NE |
| CarboplatinAlso: PARAPLATIN®IV Q3W | Drug | Carboplatin+Etoposide, Pembrolizumab+Carboplatin+Etoposide |
| EtoposideAlso: TOPOSAR™IV on Days 1, 2 and 3 of each cycle | Drug | Carboplatin+Etoposide, Pembrolizumab+Carboplatin+Etoposide |
| Belzutifan 120mgAlso: WELIREG™PO QD | Biological | Belzutifan, Pembrolizumab+Belzutifan |
Primary outcome
Percentage of Participants With a Decrease of ≥50% in Prostatic Specific Antigen (PSA)
Time frame: From Baseline Measured Every 3 Weeks Until Radiographic Progression Estimated to be Approximately 2 Years
Number of Participants with Adverse Events (AEs)
Time frame: Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Number of Participants Discontinuing Study Drug Due to AEs
Time frame: Assessed Every 3 Weeks Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
7 secondary outcomes
Disease Control Rate (DCR) Based on Prostate Cancer Working Group 3 (PCWG3)-modified RECIST 1.1 Assessed by BICR
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Overall Survival (OS)
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Duration of Response (DOR) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
ORR Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Time to PSA Progression
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Radiographic Progression-free Survival (rPFS) Based on PCWG3-modified RECIST 1.1 Assessed by BICR
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Composite Response Rate Defined as Any One of the Following: A. Response Based on RECIST 1.1; B. PSA Decrease of ≥50%; or C. Circulating Tumor-cell Count Conversion (Pembrolizumab + Olaparib Cohort Only)
Time frame: Assessed Over the Duration of the Study Which is Estimated to be Approximately 2 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Results publication: PubMed 38926066Yu EY, Ferrario C, Linch MD, Stoeckle M, Laguerre B, Arranz JA, Todenhofer T, Fong PC, Piulats JM, Berry W, Emmenegger U, Mourey L, Joshua AM, Mar N, Appleman LJ, Conter HJ, Gravis G, Li XT, Schloss C, Poehlein C, de Bono JS. Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D. Eur Urol Oncol. 2025 Jun;8(3):641-651. doi: 10.1016/j.euo.2024.05.013. Epub 2024 Jun 25.
- Results publication: PubMed 37940446Yu EY, Berry WR, Gurney H, Retz M, Conter HJ, Laguerre B, Fong PCC, Ferrario C, Todenhofer T, Gravis G, Piulats JM, Emmenegger U, Shore ND, Romano E, Mourey L, Li XT, Poehlein CH, Schloss C, Appleman LJ, de Bono JS. Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study. Eur Urol Oncol. 2024 Jun;7(3):509-518. doi: 10.1016/j.euo.2023.10.008. Epub 2023 Nov 7.
- Derived from this study: PubMed 42070919Augustin M, Laguerre B, Baldini C, Zedan AH, Gonzalez-Billalabeitia E, Fong PC, Zukov R, Hammerer P, Prentice M, Shore N, Necchi A, Todenhofer T, Kessler ER, Kose F, Gurney H, Valderrama BP, Zhu P, Imai K, Liu Y, McDermott R. Pembrolizumab Plus Lenvatinib in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort E. Eur Urol Oncol. 2026 May 2:S2588-9311(26)00084-2. doi: 10.1016/j.euo.2026.03.026. Online ahead of print.
- Derived from this study: PubMed 40796417Fong PC, Kwiatkowski M, Mosca A, Valderrama BP, Li C, Huang YH, Zedan AH, Kuc K, Wiechno P, Laguerre B, Gonzalez-Billalabeitia E, Osipov M, Sener Dede D, Goh JC, Daugaard G, Zhu P, Imai K, Liu Y, Arranz Arija JA. Vibostolimab Coformulated with Pembrolizumab in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: KEYNOTE-365 Cohort G. Eur Urol Focus. 2026 Mar;12(2):168-173. doi: 10.1016/j.euf.2025.07.018. Epub 2025 Aug 11.
- Derived from this study: PubMed 35397952Yu EY, Kolinsky MP, Berry WR, Retz M, Mourey L, Piulats JM, Appleman LJ, Romano E, Gravis G, Gurney H, Bogemann M, Emmenegger U, Joshua AM, Linch M, Sridhar S, Conter HJ, Laguerre B, Massard C, Li XT, Schloss C, Poehlein CH, de Bono JS. Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study. Eur Urol. 2022 Jul;82(1):22-30. doi: 10.1016/j.eururo.2022.02.023. Epub 2022 Apr 6.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Related trials for Metastatic Castration-Resistant Prostate Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab 200 mg, Olaparib 400 mg and Docetaxel 75 mg/m^2 in people with Metastatic Castration-Resistant Prostate Cancer, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 54 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With a Decrease of ≥50% in Prostatic Specific Antigen (PSA) (time frame: From Baseline Measured Every 3 Weeks Until Radiographic Progression Estimated to be Approximately 2 Years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02861573, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.