Trial · NCT04191096
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)
NCT04191096, Phase 3, Terminated, Merck Sharp & Dohme LLC; results first posted 2023-11-18
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. 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). Trials, record NCT04191096. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04191096
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
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)
- NCT number
- NCT04191096
- Status
- Terminated
- Phases
- Phase 3
- Enrollment
- 1,251 participants, actual
- Lead sponsor
- Merck Sharp & Dohme LLC
- Conditions
- Metastatic Hormone-Sensitive Prostate Cancer
- Interventions
- Pembrolizumab, Enzalutamide, Androgen Deprivation Therapy (ADT), Placebo
- First posted
- 2019-12-09
- Last updated
- 2026-09-28
- Other registries' IDs
- eudract:2019-003633-41
- Results first posted
- 2023-11-18
Source ClinicalTrials.gov
Registered outcomes14
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| 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) | Up to approximately 32 months | rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. |
| Primary | Overall Survival (OS) | Up to approximately 32 months | OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. |
| Secondary | Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) | Up to Approximately 32 months | TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy. |
| Secondary | Time to First Symptomatic Skeletal-related Event (TTSSRE) | Up to Approximately 32 months | TTSSRE was the time from randomization to the first symptomatic skeletal-related event 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. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment. |
| Secondary | Time to Prostate-specific Antigen (PSA) Progression | Up to Approximately 32 months | Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was 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 was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date. |
| Secondary | Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR | Up to Approximately 32 months | The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. |
| 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 | Up to Approximately 32 months | TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a \>2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score \>0 and/or currently taking opioids; a \>2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score \>4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had \> 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment. |
| 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) | Up to Approximately 32 months | PFS2 was 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. |
| Secondary | Prostate-specific Antigen (PSA) Response Rate | Up to Approximately 32 Months | PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by \>50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed \>3 weeks from the original response. |
| Secondary | Prostate-specific Antigen (PSA) Undetectable | Up to Approximately 32 Months | PSA undetectable rate was defined as the percentage of participants with detectable PSA (\> 0.2 ng/mL) at baseline, which becomes undetectable (\< 0.2 ng/mL) during study treatment. |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 registered outcomesOutcomes14
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| 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) | Up to approximately 32 months | All randomized participants | Months | MEDIAN |
| PRIMARY | Overall Survival (OS) | Up to approximately 32 months | All randomized participants | Months | MEDIAN |
| SECONDARY | Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) | Up to Approximately 32 months | All randomized participants | Months | MEDIAN |
| SECONDARY | Time to First Symptomatic Skeletal-related Event (TTSSRE) | Up to Approximately 32 months | All randomized participants | Months | MEDIAN |
| SECONDARY | Time to Prostate-specific Antigen (PSA) Progression | Up to Approximately 32 months | All randomized participants | Months | MEDIAN |
| SECONDARY | Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR | Up to Approximately 32 months | All randomized participants | Months | MEDIAN |
| 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 | Up to Approximately 32 months | All randomized participants who received at least one dose of study treatment, and who had at least 1 BPI-SF assessment | Months | MEDIAN |
| 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) | Up to Approximately 32 months | All randomized participants | Months | MEDIAN |
| SECONDARY | Prostate-specific Antigen (PSA) Response Rate | Up to Approximately 32 Months | All randomized participants who had a baseline PSA measurement and had data available for analysis | Percentage of participants | NUMBER |
| SECONDARY | Prostate-specific Antigen (PSA) Undetectable | Up to Approximately 32 Months | All randomized participants with detectable PSA at baseline and had data available for analysis | Percentage of Participants | NUMBER |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 outcomesResults by group24
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
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) | Pembrolizumab + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
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) | Placebo + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Overall Survival (OS) | Pembrolizumab + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Overall Survival (OS) | Placebo + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) | Pembrolizumab + Enzalutamide + ADT | NA | 95% Confidence Interval 29.0 to NA | Months | |
| Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) | Placebo + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Time to First Symptomatic Skeletal-related Event (TTSSRE) | Pembrolizumab + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Time to First Symptomatic Skeletal-related Event (TTSSRE) | Placebo + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Time to Prostate-specific Antigen (PSA) Progression | Pembrolizumab + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months | |
| Time to Prostate-specific Antigen (PSA) Progression | Placebo + Enzalutamide + ADT | NA | 95% Confidence Interval NA to NA | Months |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Pembrolizumab + Enzalutamide + ADT | 626 | |
| Overall Study | STARTED | Placebo + Enzalutamide + ADT | 625 | |
| Overall Study | COMPLETED | Pembrolizumab + Enzalutamide + ADT | 0 | |
| Overall Study | COMPLETED | Placebo + Enzalutamide + ADT | 0 | |
| Overall Study | NOT COMPLETED | Pembrolizumab + Enzalutamide + ADT | 626 | |
| Overall Study | NOT COMPLETED | Placebo + Enzalutamide + ADT | 625 |
Source ClinicalTrials.gov
Adverse events648
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Pembrolizumab + Enzalutamide + ADT | 97 | 625 | 139 |
| other | Anaemia | Blood and lymphatic system disorders | Placebo + Enzalutamide + ADT | 85 | 625 | 108 |
| other | Hypothyroidism | Endocrine disorders | Pembrolizumab + Enzalutamide + ADT | 82 | 625 | 82 |
| other | Hypothyroidism | Endocrine disorders | Placebo + Enzalutamide + ADT | 25 | 625 | 25 |
| other | Abdominal pain | Gastrointestinal disorders | Pembrolizumab + Enzalutamide + ADT | 32 | 625 | 41 |
| other | Abdominal pain | Gastrointestinal disorders | Placebo + Enzalutamide + ADT | 29 | 625 | 33 |
| other | Constipation | Gastrointestinal disorders | Pembrolizumab + Enzalutamide + ADT | 108 | 625 | 133 |
| other | Constipation | Gastrointestinal disorders | Placebo + Enzalutamide + ADT | 103 | 625 | 117 |
| other | Diarrhoea | Gastrointestinal disorders | Pembrolizumab + Enzalutamide + ADT | 127 | 625 | 196 |
| other | Diarrhoea | Gastrointestinal disorders | Placebo + Enzalutamide + ADT | 73 | 625 | 92 |
1 to 10 of 648Source ClinicalTrials.gov
See all 648 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Pembrolizumab + Enzalutamide + ADT | 105 | 626 |
| Total, all-cause mortality | Placebo + Enzalutamide + ADT | 93 | 625 |
| Total, other adverse events | Pembrolizumab + Enzalutamide + ADT | 588 | 625 |
| Total, other adverse events | Placebo + Enzalutamide + ADT | 551 | 625 |
| Total, serious adverse events | Pembrolizumab + Enzalutamide + ADT | 252 | 625 |
| Total, serious adverse events | Placebo + Enzalutamide + ADT | 145 | 625 |
Source ClinicalTrials.gov
Papers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 36705526 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Pembrolizumab + Enzalutamide + ADT vs Placebo + Enzalutamide + ADT: deaths from any cause | Trial comparisons |
| Pembrolizumab + Enzalutamide + ADT vs Placebo + Enzalutamide + ADT: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
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