Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)

Overview

About this study

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in patients with metastatic castrate resistant prostate cancer (mCRPC). There will be three cohorts in this study with 70 participants enrolled in each cohort: Cohort A will receive pembrolizumab + olaparib, Cohort B will receive pembrolizumab + docetaxel + prednisone, and Cohort C will receive pembrolizumab + enzalutamide. Outcome measures will be assessed individually for each cohort.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 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:
    • Cohort A 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; and
    • 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. 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.
  • Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Treatment with luteinizing hormone-releasing hormone agonists or antagonists must have been initiated ≥4 weeks prior to first dose of study therapy and must be continued throughout the study.
  • 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.
  • Women of childbearing potential and male participants must agree to use adequate contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • 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 Cohort B within 10 days of study start.  Participants in Cohort D must have a performance status of 0 or 1 on the ECOG Performance Scale.
  • 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.
  • 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.
  • 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).

Exclusion Criteria:

  • 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 (i.e., 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.
  • 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.
  • Has had a prior radium treatment or treatment with other therapeutic radiopharmaceuticals for prostate cancer.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD ligand 1 [anti-PD-L1], and 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 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.
  • For Cohort C: Has a history of seizure or any condition that may predispose to seizure.
  • 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 cytproterone within 4 weeks of the screening visit.
  • 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).

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

J Quevedo, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

J Quevedo, M.D.

Contact us for the latest status

Contact information:

No Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

J Quevedo, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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