December 5, 2019
|
December 9, 2019
|
March 1, 2021
|
February 12, 2020
|
July 2, 2026 (Final data collection date for primary outcome measure)
|
- 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 [ Time Frame: Up to approximately 77 months ]
rPFS is defined as the time from randomization to radiographic progression, or death due to any cause, whichever occurs first. rPFS according to PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm.
- Overall Survival (OS) [ Time Frame: Up to approximately 77 months ]
OS is defined as the time from randomization to death due to any cause. OS will be reported for each study arm.
|
Same as current
|
|
- Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) [ Time Frame: Up to approximately 77 months ]
TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever comes first. TFST will be reported for each study arm.
- Time to Symptomatic Skeletal-Related Event (TTSSRE) [ Time Frame: Up to approximately 77 months ]
TTSSRE is defined as the time from randomization to the first Symptomatic Skeletal-Related Event (SSRE), defined as use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. TTSSRE will be reported for each study arm.
- Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: Up to approximately 77 months ]
Time to PSA progression is defined as the time from randomization to PSA progression. The PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA progression will be reported for each study arm.
- 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) as Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 77 months ]
Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression, and will be reported for each study arm.
- 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 [ Time Frame: Up to approximately 77 months ]
TTPP is defined as the time from randomization to pain progression. In this study, pain progression will be assessed by participant responses to Item 3 of the BPI-SF ("worst pain in 24 hours") and by participant opiate use, and will be reported for each study arm.
- 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) [ Time Frame: Up to approximately 77 months ]
PFS2 is defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first. PFS2 will be reported for each study arm.
- Prostate-specific Antigen (PSA) Response Rate [ Time Frame: Up to approximately 77 months ]
PSA response rate is defined as the percentage of participants in the analysis population with PSA decline of ≥50% from baseline measured twice at least 3 weeks apart, and will be reported for each study arm.
- Prostate-specific antigen (PSA) Undetectable Rate [ Time Frame: Up to approximately 77 months ]
PSA undetectable rate is defined as the percentage of participants in the analysis population with PSA < 0.2 ng/mL during study intervention, and will be reported for each study arm.
- Objective Response Rate (ORR) 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 [ Time Frame: Up to approximately 77 months ]
ORR is defined as the percentage of participants in the analysis population who have a best overall response of either confirmed CR or PR. ORR per PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm.
- Duration of Response (DOR) 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 [ Time Frame: Up to approximately 77 months ]
DOR is defined as the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever occurs first. DOR per PCWG-modified RECIST 1.1 as assessed by Blinded Independent Central Review will be reported for each study arm.
- Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 77 months ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported for each arm.
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 77 months ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.
|
Same as current
|
Not Provided
|
Not Provided
|
|
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)
|
A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)
|
This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in 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).
|
Not Provided
|
Interventional
|
Phase 3
|
Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
|
Metastatic Hormone-Sensitive Prostate Cancer
|
- Biological: Pembrolizumab
Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.
- Drug: Enzalutamide
Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.
Other Name: XTANDI®
- Procedure: Androgen Deprivation Therapy (ADT)
Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.
- Other: Placebo
Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.
|
- Experimental: Pembrolizumab + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Interventions:
- Biological: Pembrolizumab
- Drug: Enzalutamide
- Procedure: Androgen Deprivation Therapy (ADT)
- Placebo Comparator: Placebo + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Interventions:
- Drug: Enzalutamide
- Procedure: Androgen Deprivation Therapy (ADT)
- Other: Placebo
|
Not Provided
|
|
Recruiting
|
1232
|
Same as current
|
September 1, 2026
|
July 2, 2026 (Final data collection date for primary outcome measure)
|
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 ADT with a 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:
|
Sexes Eligible for Study: |
Male |
|
18 Years and older (Adult, Older Adult)
|
No
|
|
Australia, Austria, Brazil, Canada, Chile, Colombia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Russian Federation, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
|
|
|
NCT04191096
|
3475-991 2019-003633-41 ( EudraCT Number ) MK-3475-991 ( Other Identifier: Merck ) KEYNOTE-991 ( Other Identifier: Merck ) 205267 ( Registry Identifier: Japic-CTI )
|
Yes
|
Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
|
Plan to Share IPD: |
Yes |
Plan Description: |
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
URL: |
http://engagezone.msd.com/ds_documentation.php |
|
Merck Sharp & Dohme Corp.
|
Merck Sharp & Dohme Corp.
|
Not Provided
|
Study Director: |
Medical Director |
Merck Sharp & Dohme Corp. |
|
Merck Sharp & Dohme Corp.
|
February 2021
|