Phase 3
N=186
Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension
Metastatic Hormone-Sensitive Prostate Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04934722 ↗Enrolled (actual)
186
Serious AEs
18.3%
Results posted
Nov 2023
Primary outcome: Primary: 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 (BICR) — 14.4; NA Months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pembrolizumab (Biological); Enzalutamide (Drug); Androgen Deprivation Therapy (ADT) (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Oct 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 (BICR) |
14.4; NA | — |
| PRIMARY Overall Survival (OS) |
NA; NA | — |
| SECONDARY Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) |
NA; NA | — |
| SECONDARY Time to First Symptomatic Skeletal-related Event (TTSSRE) |
NA; NA | — |
| SECONDARY Time to Prostate-specific Antigen (PSA) Progression |
NA; NA | — |
| SECONDARY Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR |
NA; NA | — |
| SECONDARY Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use |
NA; NA | — |
| SECONDARY Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2) |
NA; NA | — |
| SECONDARY Prostate-specific Antigen (PSA) Response Rate |
93.5; 98.9 | — |
| SECONDARY Prostate-specific Antigen (PSA) Undetectable |
45.6; 46.2 | — |
| SECONDARY Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR |
73.7; 65.9 | — |
| SECONDARY Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR |
NA; NA | — |
| SECONDARY Number of Participants Who Experience an Adverse Event (AE) |
— | — |
| SECONDARY Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) |
— | — |
Summary
This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in Chinese participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of Amendment 4, the study is being stopped for futility. All the prespecified interim analysis after interim analysis (IA1) and final analysis of the study described the statistical analysis plan (SAP) will not be performed. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.
Eligibility Criteria
Inclusion Criteria
- Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
- Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
- Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
- Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
- Has adequate organ function
- 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
- Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
- Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
Exclusion Criteria
- Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- 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
- Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
- Has an active infection (including tuberculosis) requiring systemic therapy
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has a history of seizure or any condition that may predispose to seizure
- Has a history of loss of consciousness within 12 months of screening
- Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
- Has hypotension (systolic blood pressure 170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
- Has a history of clinically significant ventricular arrhythmias
- Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
- Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
- Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
- 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-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received a live vaccine within 30 days prior to randomization
- Has a "
Data sourced from ClinicalTrials.gov (NCT04934722). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.