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 | Completed Phase 3 Results DMC FDA Drug

• 7 other identifiers: 3475-991MK-3475-991KEYNOTE-991jRCT20802251712023-507024-24-00U1111-1294-95922019-003633-41
• Study Type: interventional
• Target: 1,251
• Locations: 28 countries
• Sites: 230

Brief Summary

This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus Androgen Deprivation Therapy (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). As of 19-JAN-2023, the study was unblinded and all study participants stopped ongoing treatment with pembrolizumab/placebo and will continue to receive Standard of Care treatment until meeting protocol-specified discontinuation criteria if deriving clinical benefit. 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.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1),; Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  Up to approximately 32 months

• Overall Survival (OS)

  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.

  Up to approximately 32 months

Secondary Outcomes (12)

• Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)

  Up to Approximately 32 months

• Time to First Symptomatic Skeletal-related Event (TTSSRE)

  Up to Approximately 32 months

• Time to Prostate-specific Antigen (PSA) Progression

  Up to Approximately 32 months

• 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

• 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

Study Arms (2)

Pembrolizumab + Enzalutamide + ADT

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: Enzalutamide; Drug: Androgen Deprivation Therapy (ADT)

Placebo + Enzalutamide + ADT

PLACEBO COMPARATOR

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.

Drug: Enzalutamide; Drug: Androgen Deprivation Therapy (ADT); Other: Placebo

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Enzalutamide + ADT

Enzalutamide DRUG

Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.

Also known as: XTANDI®

Pembrolizumab + Enzalutamide + ADT; Placebo + Enzalutamide + ADT

Androgen Deprivation Therapy (ADT) DRUG

Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.

Pembrolizumab + Enzalutamide + ADT; Placebo + Enzalutamide + ADT

Placebo OTHER

Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Placebo + Enzalutamide + ADT

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \<86 millimeters of mercury \[mmHg\]) or uncontrolled hypertension (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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (234)

Alaska Clinical Research Center ( Site 0274)

Anchorage, Alaska, 99503, United States

Location

Providence Alaska Medical Center ( Site 0276)

Anchorage, Alaska, 99508, United States

Location

City of Hope Medical Center ( Site 0217)

Duarte, California, 91010, United States

Location

UCLA Hematology/Oncology - Santa Monica ( Site 0241)

Los Angeles, California, 90404, United States

Location

University of Colorado, Anschutz Cancer Pavilion ( Site 0236)

Aurora, Colorado, 80045, United States

Location

Hartford HealthCare Medical Group ( Site 0212)

Manchester, Connecticut, 06042, United States

Location

Smilow Cancer Center at Yale-New Haven ( Site 0250)

New Haven, Connecticut, 06510, United States

Location

Sibley Memorial Hospital ( Site 0275)

Washington D.C., District of Columbia, 20016, United States

Location

Winship Cancer Institute of Emory University ( Site 0209)

Atlanta, Georgia, 30322-1013, United States

Location

The University of Chicago ( Site 0264)

Chicago, Illinois, 60637, United States

Location

Springfield Clinic [Springfield, IL] ( Site 0240)

Springfield, Illinois, 62702, United States

Location

Cotton-O'Neil Cancer Center ( Site 0228)

Topeka, Kansas, 66606, United States

Location

The Sidney Kimmel Comprehensive Cancer Center ( Site 0204)

Baltimore, Maryland, 21287, United States

Location

St. Vincent Frontier Cancer Center-Research ( Site 0213)

Billings, Montana, 59102, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 0269)

Las Vegas, Nevada, 89169, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270)

New York, New York, 10016, United States

Location

Weill Cornell Medical College ( Site 0263)

New York, New York, 10065, United States

Location

Associated Medical Professionals of NY ( Site 0251)

Syracuse, New York, 13210, United States

Location

Duke University ( Site 0206)

Durham, North Carolina, 27710, United States

Location

TriState Urologic Services PSC Inc. dba The Urology Group ( Site 0253)

Cincinnati, Ohio, 45212, United States

Location

MidLantic Urology ( Site 0273)

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Ralph H. Johnson VA Center ( Site 0256)

Charleston, South Carolina, 29401, United States

Location

Carolina Urologic Research Center ( Site 0259)

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Associates [Nashville, TN] ( Site 0233)

Nashville, Tennessee, 37209, United States

Location

Inova Health System ( Site 0205)

Fairfax, Virginia, 22031, United States

Location

Urology of Virginia ( Site 0224)

Virginia Beach, Virginia, 23462, United States

Location

Fred Hutchinson Cancer Center ( Site 0258)

Seattle, Washington, 98109, United States

Location

Chris OBrien Lifehouse ( Site 0300)

Camperdown, New South Wales, 2050, Australia

Location

Port Macquarie Base Hospital ( Site 0301)

Port Macquarie, New South Wales, 2444, Australia

Location

Riverina Cancer Care Center ( Site 0302)

Wagga Wagga, New South Wales, 2650, Australia

Location

Gallipoli Medical Research Ltd ( Site 0309)

Greenslopes, Queensland, 4120, Australia

Location

John Flynn Hospital & Medical Centre ( Site 0308)

Tugun, Queensland, 4224, Australia

Location

Box Hill Hospital ( Site 0304)

Box Hill, Victoria, 3128, Australia

Location

Monash Health ( Site 0305)

Clayton, Victoria, 3168, Australia

Location

Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0306)

Melbourne, Victoria, 3000, Australia

Location

Fiona Stanley Hospital ( Site 0311)

Perth, Western Australia, 6150, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen ( Site 0901)

Linz, Upper Austria, 4020, Austria

Location

Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900)

Salzburg, 5020, Austria

Location

Krankenhaus der Barmherzigen Brüder Wien ( Site 0904)

Vienna, 1020, Austria

Location

Medizinische Universität Wien ( Site 0903)

Vienna, 1090, Austria

Location

Oncocentro Ceara ( Site 2309)

Fortaleza, Ceará, 60135-237, Brazil

Location

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306)

Curitiba, Paraná, 80510-130, Brazil

Location

Hospital Sao Vicente de Paulo ( Site 2303)

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Hospital de Clinicas de Porto Alegre ( Site 2304)

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Clinica de Oncologia Reichow ( Site 2308)

Blumenau, Santa Catarina, 89010-340, Brazil

Location

Fundacao Dr Amaral Carvalho ( Site 2302)

Jaú, São Paulo, 17210-120, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305)

São Paulo, 12460-000, Brazil

Location

The Ottawa Hospital ( Site 0100)

Ottawa, Ontario, K1H 8L6, Canada

Location

Niagara Health System - St. Catharines ( Site 0107)

St. Catharines, Ontario, L2S 0A9, Canada

Location

CISSS de la Monteregie-Centre ( Site 0105)

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109)

Montreal, Quebec, H2X 3E4, Canada

Location

CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106)

Montreal, Quebec, H3T 1M5, Canada

Location

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0101)

Québec, Quebec, G1J 1Z4, Canada

Location

Centro Investigación del Cáncer James Lind ( Site 2401)

Temuco, Araucania, 4800827, Chile

Location

IC La Serena Research ( Site 2406)

La Serena, Coquimbo Region, 1720430, Chile

Location

Clinica Universidad Catolica del Maule ( Site 2407)

Talca, Maule Region, 3465584, Chile

Location

Clinica Alemana ( Site 2408)

Santiago, Region M. de Santiago, 7650568, Chile

Location

Pontificia Universidad Catolica de Chile ( Site 2402)

Santiago, Region M. de Santiago, 8330024, Chile

Location

Bradfordhill ( Site 2403)

Santiago, Region M. de Santiago, 8420383, Chile

Location

Oncocentro ( Site 2400)

Viña del Mar, Valparaiso, 2520598, Chile

Location

Peking University First Hospital ( Site 0800)

Beijing, Beijing Municipality, 100034, China

Location

Beijing Cancer Hospital ( Site 0802)

Beijing, Beijing Municipality, 100142, China

Location

Chongqing Cancer Hospital ( Site 0815)

Chongqing, Chongqing Municipality, 400030, China

Location

The First Affiliated Hospital of Xiamen University ( Site 0816)

Xiamen, Fujian, 361003, China

Location

The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 0837)

Guangdong, Guangdong, 510080, China

Location

Sun Yat-Sen University Cancer Center ( Site 0825)

Guangzhou, Guangdong, 510060, China

Location

Sun Yat Sen Memorial Hospital ( Site 0819)

Guangzhou, Guangdong, 510220, China

Location

Southern Medical University Nanfang Hospital ( Site 0838)

Guangzhou, Guangdong, 510515, China

Location

Harbin Medical University Cancer Hospital ( Site 0822)

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital ( Site 0818)

Zhengzhou, Henan, 450008, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0829)

Wuhan, Hubei, 430000, China

Location

Hubei Cancer Hospital ( Site 0833)

Wuhan, Hubei, 430079, China

Location

Hunan Cancer Hospital ( Site 0817)

Changsha, Hunan, 410013, China

Location

Nanjing Drum Tower Hospital ( Site 0811)

Nanjing, Jiangsu, 210008, China

Location

The First Affiliated Hospital of Nanchang University ( Site 0821)

Nanchang, Jiangxi, 330006, China

Location

The Second Affiliated Hosp of Xi'an Jiaotong Univ College of Medicine ( Site 0831)

Xi'an, Shaanxi, 710004, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0807)

Shanghai, Shanghai Municipality, 200127, China

Location

The first affiliated Hospital of Xi an Jiaotong University ( Site 0812)

Xi’an, Shanxi, 710061, China

Location

Tianjin Medical University Cancer Institute & Hospital ( Site 0804)

Tianjin, Tianjin Municipality, 300000, China

Location

2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0808)

Hangzhou, Zhejiang, 310009, China

Location

The 1st Affil Hosp of College of Medicine, Zhejiang Univ ( Site 0830)

Hangzhou, Zhejiang, 310009, China

Location

Zhejiang Provincial People's Hospital ( Site 0809)

Hangzhou, Zhejiang, 310014, China

Location

Ningbo First Hospital-Urology ( Site 0835)

Ningbo, Zhejiang, 315010, China

Location

The First Affiliated Hospital of Wenzhou Medical University ( Site 0834)

Wenzhou, Zhejiang, 325000, China

Location

Clinica de la Costa S.A.S. ( Site 2504)

Barranquilla, Atlántico, 080020, Colombia

Location

Administradora Country SA - Clinica del Country ( Site 2507)

Bogotá, Bogota D.C., 110221, Colombia

Location

Instituto Nacional de Cancerologia E.S.E ( Site 2506)

Bogotá, Bogota D.C., 111511, Colombia

Location

Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509)

Valledupar, Cesar Department, 200001, Colombia

Location

Hemato Oncologos ( Site 2503)

Cali, Valle del Cauca Department, 760042, Colombia

Location

Rigshospitalet ( Site 1005)

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev og Gentofte Hospital. ( Site 1004)

Herlev, Capital Region, 2730, Denmark

Location

Aalborg Universitetshospital ( Site 1000)

Aalborg, North Denmark, 9000, Denmark

Location

Odense Universitetshospital ( Site 1003)

Odense, Region Syddanmark, 5000, Denmark

Location

Vejle Sygehus ( Site 1002)

Vejle, Region Syddanmark, 7100, Denmark

Location

Keski-Suomen keskussairaala ( Site 1017)

Jyväskylä, Central Finland, 40620, Finland

Location

Tampereen yliopistollinen sairaala ( Site 1022)

Tampere, Pirkanmaa, 33520, Finland

Location

HYKS ( Site 1020)

Helsinki, Southwest Finland, 00290, Finland

Location

TYKS T-sairaala Syopatautien pkl ( Site 1019)

Turku, Southwest Finland, 20520, Finland

Location

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114)

Strasbourg, Alsace, 67200, France

Location

Centre Georges Francois Leclerc ( Site 1112)

Dijon, Cote-d Or, 21079, France

Location

CHU-Jean Minjoz ( Site 1101)

Besançon, Doubs, 25000, France

Location

CHU de Brest -Site Hopital Morvan ( Site 1103)

Brest, Finistere, 29200, France

Location

Institut Bergonie ( Site 1104)

Bordeaux, Gironde, 33076, France

Location

Centre Bourgogne ( Site 1119)

Lille, Hauts-de-France, 59000, France

Location

Hopital Foch ( Site 1105)

Suresnes, Hauts-de-Seine, 92151, France

Location

C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117)

Rennes, Ille-et-Vilaine, 35033, France

Location

Institut Jean Godinot-Clinical Research Unit ( Site 1118)

Reims, Marne, 51100, France

Location

Centre D Oncologie de Gentilly ( Site 1107)

Nancy, Meurthe-et-Moselle, 54000, France

Location

Centre Leon-Berard ( Site 1110)

Lyon, Rhone, 69373, France

Location

Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102)

Pierre-Bénite, Rhone, 69310, France

Location

Hopital Henri Mondor ( Site 1116)

Créteil, Val-de-Marne, 94010, France

Location

Universitaetsklinikum Freiburg ( Site 1200)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210)

Munich, Bavaria, 81377, Germany

Location

Klinikum Rechts der Isar ( Site 1206)

München, Bavaria, 81675, Germany

Location

Klinikum Nuernberg Nord ( Site 1213)

Nuremberg, Bavaria, 90419, Germany

Location

Staedtisches Klinikum Braunschweig gGmbH ( Site 1217)

Braunschweig, Lower Saxony, 38126, Germany

Location

Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204)

Dresden, Saxony, 01307, Germany

Location

Universitaetsklinikum Magdeburg A.o.R. ( Site 1211)

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Charite Universitaetsmedizin Berlin ( Site 1201)

Berlin, 10117, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf ( Site 1212)

Hamburg, 20246, Germany

Location

St Vincents University Hospital ( Site 1300)

Dublin, Dublin, D04 T6F4, Ireland

Location

Cork University Hospital ( Site 1304)

Cork, T12 DC4A, Ireland

Location

Tallaght University Hospital ( Site 1301)

Dublin, D24 NR0A, Ireland

Location

Beaumont Hospital ( Site 1302)

Dublin, Dublin 9, Ireland

Location

University Hospital Limerick ( Site 1305)

Limerick, V94 F858, Ireland

Location

University Hospital Waterford ( Site 1303)

Waterford, X91 ER8E, Ireland

Location

Rambam Health Care Campus-Oncology Division ( Site 1400)

Haifa, 3109601, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 1404)

Jerusalem, 9112001, Israel

Location

Meir Medical Center ( Site 1401)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 1402)

Petah Tikva, 4941492, Israel

Location

Sourasky Medical Center ( Site 1403)

Tel Aviv, 6423906, Israel

Location

Yitzhak Shamir Medical Center. ( Site 1405)

Ẕerifin, 70300, Israel

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503)

Meldola, Forli-Cesena, 47014, Italy

Location

Fondazione Policlinico Universitario A. Gemelli ( Site 1512)

Rome, Lazio, 00168, Italy

Location

Istituto Clinico Humanitas Research Hospital ( Site 1500)

Rozzano, Lombardy, 20089, Italy

Location

Centro Di Riferimento Oncologico ( Site 1511)

Aviano, Pordenone, 33081, Italy

Location

IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509)

Bari, 70124, Italy

Location

Azienda Ospedaliera Cannizzaro ( Site 1501)

Catania, 95126, Italy

Location

Istituto Nazionale dei Tumori ( Site 1510)

Milan, 20133, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508)

Naples, 80131, Italy

Location

Azienda Ospedaliera Santa Maria ( Site 1502)

Terni, 05100, Italy

Location

A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504)

Verona, 37126, Italy

Location

Toho University Sakura Medical Center ( Site 0732)

Sakura, Chiba, 285-8741, Japan

Location

Ehime University Hospital ( Site 0745)

Tōon, Ehime, 791-0295, Japan

Location

Sapporo Medical University Hospital ( Site 0730)

Sapporo, Hokkaido, 060-8543, Japan

Location

Kitasato University Hospital ( Site 0734)

Sagamihara, Kanagawa, 252-0375, Japan

Location

Yokohama City University Medical Center ( Site 0735)

Yokohama, Kanagawa, 232-0024, Japan

Location

Nara Medical University Hospital ( Site 0744)

Kashihara, Nara, 634-8522, Japan

Location

Kindai University Hospital ( Site 0743)

Sayama, Osaka, 589-8511, Japan

Location

The University of Osaka Hospital ( Site 0742)

Suita, Osaka, 565-0871, Japan

Location

Saitama Medical University International Medical Center ( Site 0737)

Hidaka, Saitama, 350-1298, Japan

Location

Dokkyo Medical University Saitama Medical Center ( Site 0736)

Koshigaya, Saitama, 343-8555, Japan

Location

Hamamatsu University Hospital ( Site 0748)

Hamamatsu, Shizuoka, 431-3192, Japan

Location

Yamaguchi University Hospital ( Site 0746)

Ube, Yamaguchi, 755-8505, Japan

Location

Chiba Cancer Center ( Site 0733)

Chiba, 260-8717, Japan

Location

Harasanshin Hospital ( Site 0747)

Fukuoka, 812-0033, Japan

Location

Nagano Municipal Hospital ( Site 0731)

Nagano, 381-8551, Japan

Location

Osaka Metropolitan University Hospital ( Site 0741)

Osaka, 545-8586, Japan

Location

Toranomon Hospital ( Site 0740)

Tokyo, 105-8470, Japan

Location

Nippon Medical School Hospital ( Site 0738)

Tokyo, 113-8603, Japan

Location

Tokyo Women's Medical University ( Site 0739)

Tokyo, 162-8666, Japan

Location

Hospital San Lucas Cardiologica del Sureste ( Site 2606)

Tuxtla Gutiérrez, Chiapas, 29090, Mexico

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607)

Guadalajara, Jalisco, 44280, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua ( Site 2608)

Chihuahua City, 31000, Mexico

Location

Grupo Medico Camino SC ( Site 2613)

Mexico City, 03310, Mexico

Location

Centro Oncologico Internacional. SEDNA ( Site 2609)

Mexico City, 04700, Mexico

Location

Boca Raton Clinical Research QTO ( Site 2611)

Querétaro, 76070, Mexico

Location

Radboud University Medical Center ( Site 1606)

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Antoni van Leeuwenhoek Ziekenhuis ( Site 1603)

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Vrije Universiteit Medisch Centrum ( Site 1601)

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Isala Klinieken, Locatie Sophia ( Site 1604)

Zwolle, Overijssel, 8025 AB, Netherlands

Location

Franciscus Gasthuis en Vlietland ( Site 1605)

Schiedam, South Holland, 3118 JH, Netherlands

Location

Meander Medisch Centrum ( Site 1602)

Amersfoort, Utrecht, 3813TZ, Netherlands

Location

St. Antonius Ziekenhuis ( Site 1600)

Utrecht, 3543 AZ, Netherlands

Location

Auckland City Hospital ( Site 0321)

Auckland, 1023, New Zealand

Location

Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700)

Arequipa, Ariqipa, 04001, Peru

Location

Clinica Peruano Americana S.A. ( Site 2702)

Trujillo, La Libertad, 13011, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708)

Lima, 15033, Peru

Location

IPOR Instituto Peruano de Oncología & Radioterapia-Centro de Investigación ( Site 2706)

Lima, 15036, Peru

Location

Hospital Militar Central [Lima, Peru] ( Site 2704)

Lima, 15076, Peru

Location

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 1710)

Poznan, Greater Poland Voivodeship, 61-848, Poland

Location

Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094, Poland

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

MICS Centrum Medyczne Torun ( Site 1718)

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Szpital Uniwersytecki w Krakowie ( Site 1707)

Krakow, Lesser Poland Voivodeship, 30-688, Poland

Location

Radomskie Centrum Onkologii ( Site 1701)

Radom, Masovian Voivodeship, 26-600, Poland

Location

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700)

Przemyśl, Podkarpackie Voivodeship, 37-700, Poland

Location

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717)

Bytom, Silesian Voivodeship, 41-900, Poland

Location

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721)

Szczecin, West Pomeranian Voivodeship, 71-434, Poland

Location

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810)

Krasnoyarsk, Krasnoyarsk Krai, 660133, Russia

Location

SBIH City clinical hospital named after D.D. Pletniov ( Site 1813)

Moscow, Moscow, 105077, Russia

Location

Russian Scientific Center of Roentgenoradiology ( Site 1800)

Moscow, Moscow, 117997, Russia

Location

Volga District Medical Center Federal Medical and Biological Agency ( Site 1805)

Nizhny Novgorod, Nizhny Novgorod Oblast, 603074, Russia

Location

Omsk Clinical Oncology Dispensary ( Site 1809)

Omsk, Omsk Oblast, 644013, Russia

Location

Chonnam National University Hwasun Hospital ( Site 0406)

Jeollanam-do, Jeonranamdo, 58128, South Korea

Location

National Cancer Center ( Site 0400)

Gyeonggi-do, Kyonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital ( Site 0401)

Seongnam-si, Kyonggi-do, 13620, South Korea

Location

Kyungpook National University Chilgok Hospital ( Site 0404)

Daegu, Kyongsangbuk-do, 41404, South Korea

Location

Seoul National University Hospital ( Site 0405)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0402)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 0403)

Seoul, 05505, South Korea

Location

Instituto Catalan de Oncologia - ICO ( Site 1901)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Institut Català d'Oncologia (ICO) - Girona ( Site 1900)

Girona, Gerona, 17007, Spain

Location

Hospital Universitario Lucus Augusti ( Site 1905)

Lugo, 27003, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 1902)

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos ( Site 1906)

Madrid, 28040, Spain

Location

Hospital 12 de Octubre de Madrid ( Site 1903)

Madrid, 28041, Spain

Location

Hospital Virgen de la Macarena ( Site 1904)

Seville, 41009, Spain

Location

Kantonsspital St. Gallen ( Site 2000)

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

CHUV (centre hospitalier universitaire vaudois) ( Site 2002)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Universitaetsspital Zuerich ( Site 2001)

Zurich, Canton of Zurich, 8091, Switzerland

Location

Kantonsspital Graubuenden ( Site 2003)

Chur, Kanton Graubünden, 7000, Switzerland

Location

Kaohsiung Chang Gung Memorial Hospital ( Site 0504)

Kaohsiung City, 83301, Taiwan

Location

National Cheng Kung University Hospital ( Site 0503)

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital ( Site 0500)

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital ( Site 0501)

Taipei, 11217, Taiwan

Location

Chang Gung Medical Foundation. Linkou ( Site 0502)

Taoyuan District, 33305, Taiwan

Location

Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600)

Bangkok, Bangkok, 10330, Thailand

Location

Ramathibodi Hospital. ( Site 0601)

Bangkok, Bangkok, 10400, Thailand

Location

Faculty of Medicine Siriraj Hospital ( Site 0602)

Bangkok, Bangkok, 10700, Thailand

Location

Srinagarind Hospital ( Site 0604)

Khon Kaen, 40002, Thailand

Location

Ankara Bilkent Sehir Hastanesi ( Site 2103)

Ankara, Adana, 06800, Turkey (Türkiye)

Location

Acibadem Adana Hastanesi ( Site 2106)

Adana, 01130, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi. ( Site 2101)

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Universitesi Tıp Fakultesi ( Site 2105)

Ankara, 06230, Turkey (Türkiye)

Location

Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100)

Istanbul, 34098, Turkey (Türkiye)

Location

Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102)

Izmir, 35100, Turkey (Türkiye)

Location

Konya Necmettin Erbakan University Medical Faculty ( Site 2104)

Konya, 42080, Turkey (Türkiye)

Location

Aberdeen Royal Infirmary ( Site 1315)

Aberdeen, Aberdeen City, AB25 2ZN, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust ( Site 1317)

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

University College London Hospitals NHS Foundation Trust ( Site 1320)

London, London, City of, NW1 2BU, United Kingdom

Location

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1318)

London, London, City of, SW3 6JJ, United Kingdom

Location

Velindre Cancer Centre Hospital ( Site 1322)

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Related Publications (1)

• Gratzke C, Kwiatkowski M, De Giorgi U, Martins da Trindade K, De Santis M, Armstrong AJ, Niu C, Liu Y, Poehlein CH. KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer. Future Oncol. 2023 Jan 27. doi: 10.2217/fon-2022-0776. Online ahead of print.

  PMID: 36705526 DERIVED

Related Links

• Merck Oncology Clinical Trial Information
• Plain Language Summary

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; enzalutamide; Androgen Antagonists

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 9, 2019
• Study Start: February 12, 2020
• Primary Completion: October 31, 2022
• Study Completion: April 8, 2026
• Last Updated: April 29, 2026
• Results First Posted: November 18, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (7); CA (6); PL (10); GB (5); CO (5); NL (7); JP (19); CL (7); TW (5); FI (4); RU (5); IL (6); BR (7); TH (4); AU (9); KR (7); US (27); TU (7); PE (5); CN (24); FR (13); DE (9); NZ (1); CH (4); IT (10); ME (6); IE (6); DK (5)