Prostatic Neoplasms
Conditions
Interventions
investigational material(s)
Generic name etc : Pembrolizumab + Enzalutamide
INN of investigational material : pembrolizumab, enzalutamide
Therapeutic category code : 429 Other antitumor agents
Dosage
Sponsors
MSD K.K.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology 2) Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization 3) Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI) 4) Has met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naive; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression) 5) Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM) 6) Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization 7) Participants must agree to the following during the study treatment period and for at least 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom 8) Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample 9) Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
Exclusion criteria
Exclusion criteria: 1) Has a known additional malignancy that is progressing or has required active treatment in the last 3 years 2) Has an active autoimmune disease that has required systemic treatment in past 2 years 3) Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy 4) Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications 5) Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules 6) Has an active infection (including tuberculosis) requiring systemic therapy 7) Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease 8) Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection 9) Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis 10) Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients 11) Has a history of seizure or any condition that may predispose to seizure 12) Has a history of loss of consciousness within 12 months of screening 13) Has hypotension (systolic blood pressure 170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit 14) Has bradycardia (heart rate of <50 beats per minute) on the screening electrocardiogram (ECG) 15) Has history of prostate cancer progression on ketoconazole 16) Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate 17) Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor 18) Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer 19) Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC 20) Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization 21) Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization 22) Has received a live or live attenuated vaccine within 30 days prior to randomization 23) Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment 24) Has a "superscan" bone scan 25) Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of enzalutamide 26) Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy - Overall Survival (OS): OS was defined as the time from randomization to death due to any cause. - Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review: rPFS was defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurred first. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy - Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) - Prostate-specific Antigen (PSA) Response Rate - Objective Response (OR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review - Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review - Time to Prostate-specific Antigen (PSA) Progression - Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review - Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score) - Time to First Symptomatic Skeletal-related Event (SSRE) - Number of Participants Who Experience an Adverse Event (AE) - Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | — |
Countries
Asia except Japan, Japan, North America, Oceania, South America
Contacts
Public ContactMSDJRCT inquiry mailbox
MSD K.K.
Outcome results
None listed