Clinical Trials List
Protocol NumberMK-3475-991
NCT Number(ClinicalTrials.gov Identfier)NCT04191096
Active
2020-01-01 - 2027-07-31
Phase III
Recruiting5
ICD-10C61
Malignant neoplasm of prostate
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9185
Malignant neoplasm of prostate
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)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Tzu-Hao Huang Division of Urology
- 潘競成 Division of Others
- Yen-Hwa Chang Division of Urology
- 朱力行 Division of Nuclear Medicine
- Tzu-Ping Lin Division of Urology
- 陳威任 Division of Urology
- Tzu-chun Wei Division of Urology
- Yi-Hsiu Huang Division of Urology
- 沈書慧 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yung-Chang Lin Division of Hematology & Oncology
- I-hung Shao Division of Urology
- 吳燿宇 Division of Radiation Therapy
- 洪宗民 Division of Radiation Therapy
- Kai-Jie Yu Division of Urology
- 沈鼎文 Division of Radiology
- 張境夫 Division of Hematology & Oncology
- See-Tong Pang Division of Urology
- Hong-Cheng Gan Division of Urology
- 黃文冠 Division of Hematology & Oncology
- 林柏宏 Division of Urology
- Jing-Ren Tseng Division of Nuclear Medicine
- 詹頂立 Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Che-Yuan Hu Division of Urology
- Wu-Chou Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Yuh-Shyan Tsai Division of Urology
- Jiann-Hui Ou Division of Urology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- 康智雄 Division of Urology
- 羅浩倫 Division of Urology
- 吳佳哲 Division of Hematology & Oncology
- 鄭元佐 Division of Urology
- 林偉雄 Division of Radiology
- 陳彥豪 Division of Hematology & Oncology
- 陳彥達 Division of Urology
- 常景棣 Division of Radiology
- 賴香蘭 Division of Hematology & Oncology
- 王弘仁 Division of Urology
- 徐健欽 Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- CHUNG-HSIN CHEN Division of Urology
- JIAN-HUA HONG Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
- Hong-Chiang Chang Division of Urology
- YI-KAI CHANG Division of Urology
- Chia-Hsien Chen Division of Hematology & Oncology
- CHING-CHU LU Division of Nuclear Medicine
- Yeong-Shiau Pu Division of Urology
- PO-MING CHOW Division of Urology
- 馮國剛 Division of Urology
- - - Division of Radiology
- 劉詩彬 Division of Urology
- YU-CHUAN LU Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- 王中傑 Division of Others
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Objectives
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).
Test Drug
Keytruda®
Xtandi®
Xtandi®
Active Ingredient
Enzalutamide
Pembrolizumab
Pembrolizumab
Dosage Form
IVT
capsule/tablet
capsule/tablet
Dosage
100
40, 40, 80
40, 40, 80
Endpoints
Primary Outcome Measures :
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.
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.
Inclution Criteria
1. Has histologically- or cytologically-confirmed (if acceptable according to local health
authority regulations) adenocarcinoma of the prostate without small cell histology.
Diagnosis must be stated in a pathology report and confirmed by the investigator.
2. Has metastatic disease as assessed by investigator and verified by BICR (prior to
randomization) by either ≥2 bone lesions on bone scan and/or visceral disease (eg, lung
or liver) by CT/MRI. Participants whose metastatic disease is limited to lymph nodes are
not eligible.
3. Once randomized, participant must be willing to maintain continuous ADT with a LHRH
agonists or antagonists during study treatment or have a history of bilateral orchiectomy.
4. Has an ECOG performance status of 0 or 1 assessed within 10 days of randomization.
5. Participants receiving bone resorptive therapy (including, but not limited to,
bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to
randomization.
6. Demonstrates adequate organ function as defined in Table 4; all screening labs should be
performed in central laboratory within 10 days of the first dose of study intervention.
7. Is male, ≥18 years of age at the time of signing the informed consent
8. Male participants are eligible to participate if they 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 as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception, unless confirmed to be azoospermic (vasectomized
or secondary to medical cause [Appendix 5]), as detailed below:
• Agree to use a male condom plus partner use of an additional contraceptive
method when having penile-vaginal intercourse with a WOCBP who is not
currently pregnant. Note: Men with a pregnant or breastfeeding partner must
agree to remain abstinent from penile-vaginal intercourse or use a male condom
during each episode of penile-vaginal penetration.
9. 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.
10. The participant (or legally acceptable representative if applicable) provides written
informed consent/assent for the study.
(please review protocol Section 5.1)
authority regulations) adenocarcinoma of the prostate without small cell histology.
Diagnosis must be stated in a pathology report and confirmed by the investigator.
2. Has metastatic disease as assessed by investigator and verified by BICR (prior to
randomization) by either ≥2 bone lesions on bone scan and/or visceral disease (eg, lung
or liver) by CT/MRI. Participants whose metastatic disease is limited to lymph nodes are
not eligible.
3. Once randomized, participant must be willing to maintain continuous ADT with a LHRH
agonists or antagonists during study treatment or have a history of bilateral orchiectomy.
4. Has an ECOG performance status of 0 or 1 assessed within 10 days of randomization.
5. Participants receiving bone resorptive therapy (including, but not limited to,
bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to
randomization.
6. Demonstrates adequate organ function as defined in Table 4; all screening labs should be
performed in central laboratory within 10 days of the first dose of study intervention.
7. Is male, ≥18 years of age at the time of signing the informed consent
8. Male participants are eligible to participate if they 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 as their preferred and usual lifestyle
(abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception, unless confirmed to be azoospermic (vasectomized
or secondary to medical cause [Appendix 5]), as detailed below:
• Agree to use a male condom plus partner use of an additional contraceptive
method when having penile-vaginal intercourse with a WOCBP who is not
currently pregnant. Note: Men with a pregnant or breastfeeding partner must
agree to remain abstinent from penile-vaginal intercourse or use a male condom
during each episode of penile-vaginal penetration.
9. 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.
10. The participant (or legally acceptable representative if applicable) provides written
informed consent/assent for the study.
(please review protocol Section 5.1)
Exclusion Criteria
1. Has a known additional malignancy that is progressing or has required active treatment in
the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ that have undergone potentially curative
therapy are not excluded.
2. Has an active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment.
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study intervention.
4. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant’s participation
for the full duration of the study, or is not in the best interest of the participant to
participate, in the opinion of the treating investigator.
5. 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.
6. Has a gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer
disease within last 3 months).
7. Is unable to swallow tablets/capsules.
8. Has an active infection (including tuberculosis) requiring systemic therapy.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
10. Has known active HIV, hepatitis B virus (eg, hepatitis B surface antigen reactive) or
HCV (eg, HCV RNA [qualitative] is detected). Testing for Hepatitis B and Hepatitis C is
not required unless mandated by local regulation.
11. Has known or suspected CNS metastases and/or carcinomatous meningitis.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.
13. Has a history of seizure or any condition that may predispose to seizure (including, but
not limited to prior cerebrovascular accident, transient ischemic attack, or brain
arteriovenous malformation; or intracranial masses such as a schwannoma or
meningioma that is causing edema or mass effect).
14. Has a history of loss of consciousness within 12 months of the Screening Visit.
15. Has had myocardial infarction or uncontrolled angina within 6 months prior to
randomization.
Note: Participants with recent history of revascularization for acute coronary syndrome
within 3 months prior to randomization are included.
16. 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 unless a screening
echocardiogram or multigated acquisition scan performed within 3 months prior to
randomization date demonstrates a left ventricular ejection fraction >45%.
17. Has a history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, torsades de pointes).
18. Has a history of Mobitz II second degree or third degree heart block without a permanent
pacemaker in place.
19. Has hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mm
Hg) at the Screening Visit.
20. Has bradycardia as indicated by a heart rate of <50 beats per minute on the Screening
ECG.
21. Has uncontrolled hypertension as indicated by systolic blood pressure >170 mm Hg or
diastolic blood pressure >105 mm Hg at the Screening visit.
22. Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients.
(please review protocol Section 5.2)
the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ that have undergone potentially curative
therapy are not excluded.
2. Has an active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment.
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study intervention.
4. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant’s participation
for the full duration of the study, or is not in the best interest of the participant to
participate, in the opinion of the treating investigator.
5. 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.
6. Has a gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer
disease within last 3 months).
7. Is unable to swallow tablets/capsules.
8. Has an active infection (including tuberculosis) requiring systemic therapy.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
10. Has known active HIV, hepatitis B virus (eg, hepatitis B surface antigen reactive) or
HCV (eg, HCV RNA [qualitative] is detected). Testing for Hepatitis B and Hepatitis C is
not required unless mandated by local regulation.
11. Has known or suspected CNS metastases and/or carcinomatous meningitis.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.
13. Has a history of seizure or any condition that may predispose to seizure (including, but
not limited to prior cerebrovascular accident, transient ischemic attack, or brain
arteriovenous malformation; or intracranial masses such as a schwannoma or
meningioma that is causing edema or mass effect).
14. Has a history of loss of consciousness within 12 months of the Screening Visit.
15. Has had myocardial infarction or uncontrolled angina within 6 months prior to
randomization.
Note: Participants with recent history of revascularization for acute coronary syndrome
within 3 months prior to randomization are included.
16. 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 unless a screening
echocardiogram or multigated acquisition scan performed within 3 months prior to
randomization date demonstrates a left ventricular ejection fraction >45%.
17. Has a history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, torsades de pointes).
18. Has a history of Mobitz II second degree or third degree heart block without a permanent
pacemaker in place.
19. Has hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mm
Hg) at the Screening Visit.
20. Has bradycardia as indicated by a heart rate of <50 beats per minute on the Screening
ECG.
21. Has uncontrolled hypertension as indicated by systolic blood pressure >170 mm Hg or
diastolic blood pressure >105 mm Hg at the Screening visit.
22. Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients.
(please review protocol Section 5.2)
The Estimated Number of Participants
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Taiwan
35 participants
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Global
1232 participants
