Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)

NCT03834493 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 7 other identifiers: 3475-641MK-3475-641KEYNOTE-6411950052022-500785-10-00U1111-1278-11512018-004117-40
• Study Type: interventional
• Target: 1,244
• Locations: 27 countries
• Sites: 249

Brief Summary

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and enzalutamide in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve, or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to 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.

Conditions

Prostatic Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause. The OS for all participants is presented.

  Up to 40 months (through database cut-off date of 12-Dec-2022)

• 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

  rPFS was defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurred first. The rPFS per PCWG-modified RECIST for all participants is presented.

  Up to 40 months (through database cut-off date of 12-Dec-2022)

Secondary Outcomes (11)

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

  Up to 40 months (through database cut-off date of 12-Dec-2022)

• Prostate-specific Antigen (PSA) Response Rate

  Up to 40 months (through database cut-off date of 12-Dec-2022)

• Prostate-specific Antigen (PSA) Undetectable Rate

  Up to 40 months (through database cut-off date of 12-Dec-2022)

• Objective Response (OR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review

  Up to 40 months (through database cut-off date of 12-Dec-2022)

• Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review

  Up to 40 months (through database cut-off date of 12-Dec-2022)

Study Arms (2)

Pembrolizumab + Enzalutamide

EXPERIMENTAL

Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered orally (PO) once a day (QD) continuously until progression.

Biological: Pembrolizumab; Drug: Enzalutamide

Placebo + Enzalutamide

PLACEBO COMPARATOR

Participants receive placebo by IV infusion administered on Day 1 Q3W for up to 35 cycles (approximately 2 years) PLUS enzalutamide 160 mg administered PO QD continuously until progression.

Drug: Enzalutamide; Drug: Placebo

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Enzalutamide

Enzalutamide DRUG

Capsules/Tablets

Also known as: XTANDI®

Pembrolizumab + Enzalutamide; Placebo + Enzalutamide

Placebo DRUG

IV infusion

Also known as: Normal saline or dextrose infusion

Placebo + Enzalutamide

Eligibility Criteria

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

You may not qualify if:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression)
• Has ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<2.0 nM)
• Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
• Participants must agree to the following during the study treatment period and for at least 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom
• 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
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (259)

University of South Alabama, Mitchell Cancer Institute ( Site 0065)

Mobile, Alabama, 36604, United States

Location

Providence Medical Foundation-Oncology ( Site 0069)

Fullerton, California, 92835, United States

Location

UCLA Hematology/Oncology - Santa Monica ( Site 0081)

Los Angeles, California, 90404, United States

Location

University of Colorado Cancer Center ( Site 0022)

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital at Yale New Haven ( Site 0038)

New Haven, Connecticut, 06513, United States

Location

Moffitt Cancer Center ( Site 0080)

Tampa, Florida, 33612, United States

Location

Georgia Cancer Center at Augusta University ( Site 0026)

Augusta, Georgia, 30912, United States

Location

Mount Sinai Hospital ( Site 0042)

Chicago, Illinois, 60608, United States

Location

Methodist Hospitals. ( Site 0008)

Merrillville, Indiana, 46410, United States

Location

Tulane Cancer Center ( Site 0066)

New Orleans, Louisiana, 70112, United States

Location

University of Massachusetts Worcester ( Site 0053)

Worcester, Massachusetts, 01655, United States

Location

Cancer & Hematology Centers of Western Michigan ( Site 0013)

Grand Rapids, Michigan, 49503, United States

Location

Munson Medical Center ( Site 0030)

Traverse City, Michigan, 49684, United States

Location

St. Vincent Frontier Cancer Center ( Site 0016)

Billings, Montana, 59102, United States

Location

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0034)

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 0092)

Las Vegas, Nevada, 89169, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)

Hackensack, New Jersey, 07601, United States

Location

Associated Medical Professionals of NY ( Site 0060)

Syracuse, New York, 13210, United States

Location

W. G. Bill Hefner VA Medical Center ( Site 0029)

Salisbury, North Carolina, 28144, United States

Location

Gabrail Cancer Center-Research ( Site 0096)

Canton, Ohio, 44718, United States

Location

Tri-State Urologic Services PSC, Inc. ( Site 0094)

Cincinnati, Ohio, 45212, United States

Location

University Hospitals Cleveland Medical Center ( Site 0036)

Cleveland, Ohio, 44106, United States

Location

Oregon Health Science University ( Site 0031)

Portland, Oregon, 97239, United States

Location

Carolina Urologic Research Center ( Site 0070)

Myrtle Beach, South Carolina, 29572, United States

Location

Inova Schar Cancer Institute ( Site 0006)

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Institute ( Site 0052)

Richmond, Virginia, 23230, United States

Location

Blue Ridge Cancer Care ( Site 0086)

Roanoke, Virginia, 24014, United States

Location

Froedtert Hospital & the Medical College of Wisconsin ( Site 0045)

Milwaukee, Wisconsin, 53226, United States

Location

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)

Berazategui, Buenos Aires, B1884BBF, Argentina

Location

Organizacion Medica de Investigacion ( Site 1019)

CABA, Buenos Aires, C1015ABO, Argentina

Location

Instituto Medico Alexander Fleming ( Site 1010)

Ciudad Autonoma de Buenos Aires., Buenos Aires, C1426ANZ, Argentina

Location

Instituto de Investigaciones Clinicas ( Site 1000)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

Location

Centro de Diagnostico Urologico ( Site 1008)

Buenos Aires, Buenos Aires F.D., C1120AAT, Argentina

Location

Sanatorio Parque ( Site 1002)

Rosario, Santa Fe Province, S2000DSV, Argentina

Location

Instituto de Oncologia de Rosario ( Site 1015)

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)

Buenos Aires, C1012AAR, Argentina

Location

Hospital Aleman ( Site 1004)

Buenos Aires, C1118AAT, Argentina

Location

Centro Medico Dra De Salvo ( Site 1018)

Buenos Aires, C1426ABP, Argentina

Location

CEMAIC ( Site 1014)

Córdoba, X5008HHW, Argentina

Location

Centro Oncologico Riojano Integral ( Site 1005)

La Rioja, F5300COE, Argentina

Location

Centro Oncologico de Integracion Regional. COIR ( Site 1007)

Mendoza, M5500AYB, Argentina

Location

St. Vincent's Hospital ( Site 0158)

Darlinghurst, New South Wales, 2010, Australia

Location

St George Hospital ( Site 0157)

Kogarah, New South Wales, 2217, Australia

Location

Macquarie University ( Site 0151)

Macquarie University, New South Wales, 2109, Australia

Location

Port Macquarie Base Hospital ( Site 0153)

Port Macquarie, New South Wales, 2444, Australia

Location

Calvary Mater Newcastle ( Site 0148)

Waratah, New South Wales, 2298, Australia

Location

Gallipoli Medical Research Ltd ( Site 0149)

Greenslopes, Queensland, 4120, Australia

Location

Gold Coast University Hospital ( Site 0150)

Southport, Queensland, 4215, Australia

Location

Royal Adelaide Hospital ( Site 0154)

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre ( Site 0147)

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital ( Site 0162)

Perth, Western Australia, 6150, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)

Linz, Upper Austria, 4020, Austria

Location

Medizinische Universität Wien ( Site 0375)

Vienna, 1090, Austria

Location

Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1036)

Curitiba, Paraná, 81520-060, Brazil

Location

Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1032)

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 1038)

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)

Itajaí, Santa Catarina, 88301-215, Brazil

Location

Hospital de Base de Sao Jose de Rio Preto ( Site 1022)

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

A.C. Camargo Cancer Center ( Site 1026)

São Paulo, 01509-900, Brazil

Location

Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1040)

São Paulo, 04014-002, Brazil

Location

MHAT Serdika-Second Department of Medical Oncology ( Site 0505)

Sofia, Sofia (stolitsa), 1301, Bulgaria

Location

MHAT Central Hospital ( Site 0503)

Plovdiv, 4000, Bulgaria

Location

Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0507)

Plovdiv, 4004, Bulgaria

Location

BC Cancer Victoria-Clinical Trials Unit ( Site 0111)

Victoria, British Columbia, V8R 6V5, Canada

Location

Health Sciences North ( Site 0122)

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)

Hamilton, Ontario, L8V 5C2, Canada

Location

Grand River Hospital ( Site 0120)

Kitchener, Ontario, N2G 1G3, Canada

Location

Lakeridge Health ( Site 0117)

Oshawa, Ontario, L1G 2B9, Canada

Location

Sunnybrook Research Institute ( Site 0108)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0107)

Toronto, Ontario, M5G 2M9, Canada

Location

CISSS de la Monteregie-Centre ( Site 0119)

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)

Montreal, Quebec, H2X 3E4, Canada

Location

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0103)

Québec, Quebec, G1J 1Z4, Canada

Location

CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)

Rimouski, Quebec, G5L 5T1, Canada

Location

CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Fundacion Arturo Lopez Perez ( Site 1049)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Pontificia Universidad Catolica de Chile ( Site 1047)

Santiago, Region M. de Santiago, 8330024, Chile

Location

Bradfordhill ( Site 1044)

Santiago, Region M. de Santiago, 8420383, Chile

Location

Centro Investigación del Cáncer James Lind ( Site 1041)

Temuco, Región de la Araucanía, 4800827, Chile

Location

Rey y Oreilly Limitada ( Site 1048)

Temuco, Región de la Araucanía, 4810148, Chile

Location

Oncocentro ( Site 1045)

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Hospital Pablo Tobon Uribe ( Site 1066)

Medellín, Antioquia, 050034, Colombia

Location

Biomelab S A S ( Site 1067)

Barranquilla, Atlántico, 080001, Colombia

Location

Clinica de la Costa S.A.S. ( Site 1073)

Barranquilla, Atlántico, 080020, Colombia

Location

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)

Bogotá, Bogota D.C., 110311, Colombia

Location

Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)

Valledupar, Cesar Department, 200001, Colombia

Location

Oncomédica S.A.S ( Site 1057)

Montería, Departamento de Córdoba, 230002, Colombia

Location

Clínica Imbanaco S.A.S ( Site 1064)

Cali, Valle del Cauca Department, 760042, Colombia

Location

Hemato Oncologos S.A. ( Site 1065)

Cali, Valle del Cauca Department, 760042, Colombia

Location

Fakultni Nemocnice u sv. Anny v Brne-Onkologicko-chirurgicke oddeleni ( Site 1303)

Brno, Brno-mesto, 656 91, Czechia

Location

Nemocnice AGEL Novy Jicin a.s. ( Site 1304)

Nový Jičín, Novy Jicin, 741 01, Czechia

Location

Fakultni nemocnice Olomouc ( Site 1301)

Olomouc, Olomoucký kraj, 779 00, Czechia

Location

C.H. de Saint Quentin ( Site 0481)

Saint-Quentin, Aisne, 02321, France

Location

Centre Jean Perrin ( Site 0434)

Clermont-Ferrand, Auvergne, 63011, France

Location

Clinique Sainte Anne ( Site 0431)

Strasbourg, Bas-Rhin, 67000, France

Location

CHU de Brest -Site Hopital Morvan ( Site 0441)

Brest, Brittany Region, 29200, France

Location

CHU Jean Minjoz ( Site 0423)

Besançon, Doubs, 25000, France

Location

Institut Bergonie ( Site 0421)

Bordeaux, Gironde, 33076, France

Location

Institut Claudius Regaud IUCT Oncopole ( Site 0418)

Toulouse, Haute-Garonne, 31059, France

Location

Hopital Foch ( Site 0428)

Suresnes, Hauts-de-Seine, 92150, France

Location

Institut Regional du Cancer de Montpellier - ICM ( Site 0443)

Montpellier, Herault, 34298, France

Location

Institut De Cancerologie De L Ouest ( Site 0448)

Saint-Herblain, Loire-Atlantique, 44805, France

Location

Centre Hospitalier Regional du Orleans ( Site 0430)

Orléans, Loiret, 45100, France

Location

Centre D Oncologie de Gentilly ( Site 0432)

Nancy, Meurthe-et-Moselle, 54000, France

Location

Centre Hospitalier de Valenciennes ( Site 0439)

Valenciennes, Nord, 59300, France

Location

C.H.U. Lyon Sud ( Site 0436)

Pierre-Bénite, Rhone, 69310, France

Location

CHU Amiens Picardie Site Sud Amiens ( Site 0438)

Amiens, Somme, 80000, France

Location

Institut Gustave Roussy ( Site 0416)

Villejuif, Val-de-Marne, 94800, France

Location

Institut Sainte Catherine ( Site 0447)

Avignon, Vaucluse, 84918, France

Location

Institut Mutualiste Montsouris ( Site 0446)

Paris, 75014, France

Location

Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Studienpraxis Urologie ( Site 0309)

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Universitaetsklinik fuer Urologie ( Site 0307)

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Klinikum Rechts der Isar ( Site 0300)

Munich, Bavaria, 81675, Germany

Location

Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)

Nuremberg, Bavaria, 90419, Germany

Location

Universitaetsklinikum Goettingen ( Site 0345)

Göttingen, Lower Saxony, 37075, Germany

Location

Uniklinik RWTH Aachen ( Site 0308)

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitaetsklinikum Muenster ( Site 0320)

Münster, North Rhine-Westphalia, 48149, Germany

Location

Krankenhaus der Barmherzigen Brueder Trier ( Site 0310)

Trier, Rhineland-Palatinate, 54292, Germany

Location

Universitaetsklinikum des Saarlandes ( Site 0348)

Homburg, Saarland, 66421, Germany

Location

Universitaetsklinikum Schleswig Holstein. ( Site 0346)

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitaetsklinikum Jena ( Site 0305)

Jena, Thuringia, 07747, Germany

Location

Charite Universitaetsmedizin Berlin ( Site 0301)

Berlin, 10117, Germany

Location

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1321)

Kecskemét, Bács-Kiskun county, 6000, Hungary

Location

Petz Aladár Megyei Oktató Kórház-Onkológiai Osztály ( Site 1324)

Győr, Győr-Moson-Sopron, 9024, Hungary

Location

Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 1325)

Budapest, Pest County, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 1326)

Budapest, 1062, Hungary

Location

Beaumont Hospital ( Site 0726)

Dublin, D09 V2N0, Ireland

Location

Tallaght University Hospital ( Site 0730)

Dublin, D24 NROA, Ireland

Location

Mid Western Cancer Centre ( Site 0728)

Limerick, V98F858, Ireland

Location

HaEmek Medical Center ( Site 0548)

Afula, 1834111, Israel

Location

Assuta Ashdod Medical Center ( Site 0550)

Ashdod, 7747629, Israel

Location

Soroka Medical Center ( Site 0549)

Beersheba, 8410101, Israel

Location

Rambam Health Care Campus-Oncology Division ( Site 0543)

Haifa, 3109601, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 0546)

Jerusalem, 9112001, Israel

Location

Meir Medical Center ( Site 0544)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 0545)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 0541)

Ramat Gan, 5262000, Israel

Location

Sourasky Medical Center ( Site 0542)

Tel Aviv, 6423906, Israel

Location

Yitzhak Shamir Medical Center. ( Site 0547)

Ẕerifin, 70300, Israel

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 0464)

Meldola, Emilia-Romagna, 47014, Italy

Location

A.O. Universitaria di Modena ( Site 0454)

Modena, Emilia-Romagna, 41124, Italy

Location

Istituto Clinico Humanitas Research Hospital ( Site 0452)

Rozzano, Lombardy, 20089, Italy

Location

Presidio Ospedaliero S. Maria Delle Grazie-U.O.C. ONCOLOGIA ( Site 0802)

Pozzuoli, Napoli, 80078, Italy

Location

Centro Di Riferimento Oncologico ( Site 0800)

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0465)

Verona, Veneto, 37134, Italy

Location

Medical Oncology Ospedale San Donato ( Site 0461)

Arezzo, 52100, Italy

Location

Ospedale Policlinico S. Orsola-Malpighi ( Site 0453)

Bologna, 40138, Italy

Location

Azienda Ospedaliera Cannizzaro ( Site 0458)

Catania, 95126, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0462)

Napoli, 80131, Italy

Location

Azienda Ospedaliera San Camillo Forlanini ( Site 0455)

Roma, 00152, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli ( Site 0801)

Roma, 00168, Italy

Location

Azienda Ospedaliera Santa Maria Terni ( Site 0456)

Terni, 05100, Italy

Location

Az. Osp. Univ. Sta Maria della Misericordia di Udine ( Site 0460)

Udine, 33100, Italy

Location

National Cancer Center Hospital East ( Site 0702)

Kashiwa, Chiba, 2778577, Japan

Location

Toho University Sakura Medical Center ( Site 0703)

Sakura, Chiba, 285-8741, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 0716)

Matsuyama, Ehime, 791-0280, Japan

Location

Iizuka Hospital ( Site 0744)

Iizuka, Fukuoka, 820-8505, Japan

Location

Hakodate Goryoukaku Hospital ( Site 0739)

Hakodate, Hokkaido, 040-8611, Japan

Location

Kanazawa University Hospital ( Site 0701)

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Kitasato University Hospital ( Site 0705)

Sagamihara, Kanagawa, 252-0375, Japan

Location

Yokohama City University Medical Center ( Site 0706)

Yokohama, Kanagawa, 232-0024, Japan

Location

Miyagi Cancer Center ( Site 0747)

Natori-shi, Miyagi, 981-1293, Japan

Location

Nara Medical University Hospital ( Site 0715)

Kashihara, Nara, 634-8522, Japan

Location

Kindai University Hospital ( Site 0714)

Sayama, Osaka, 589-8511, Japan

Location

The University of Osaka Hospital ( Site 0713)

Suita, Osaka, 565-0871, Japan

Location

Saitama Medical University International Medical Center ( Site 0708)

Hidaka, Saitama, 350-1298, Japan

Location

Saitama Medical Center ( Site 0743)

Kawagoe, Saitama, 350-8550, Japan

Location

Dokkyo Medical University Saitama Medical Center ( Site 0707)

Koshigaya, Saitama, 343-8555, Japan

Location

Hamamatsu University Hospital ( Site 0720)

Hamamatsu, Shizuoka, 431-3192, Japan

Location

Yamaguchi University Hospital ( Site 0717)

Ube, Yamaguchi, 755-8505, Japan

Location

Chiba Cancer Center ( Site 0704)

Chiba, 260-8717, Japan

Location

Kyushu University Hospital ( Site 0718)

Fukuoka, 812-8582, Japan

Location

Hiroshima Prefectural Hospital ( Site 0748)

Hiroshima, 734-8530, Japan

Location

University of Miyazaki Hospital ( Site 0721)

Miyazaki, 889-1692, Japan

Location

Nagasaki University Hospital ( Site 0719)

Nagasaki, 852-8510, Japan

Location

Toranomon Hospital ( Site 0711)

Tokyo, 105-8470, Japan

Location

Nippon Medical School Hospital ( Site 0709)

Tokyo, 113-8603, Japan

Location

Keio University Hospital ( Site 0710)

Tokyo, 160-8582, Japan

Location

Radboud University Medical Center ( Site 0470)

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Maastricht University Medical Centre ( Site 0467)

Maastricht, Limburg, 6229 HX, Netherlands

Location

Amphia Hospital Location Molengracht ( Site 0474)

Breda, North Brabant, 4818 CK, Netherlands

Location

Catharina Ziekenhuis ( Site 0472)

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

Noordwest Ziekenhuisgroep NWZ ( Site 0468)

Alkmaar, North Holland, 1815 JD, Netherlands

Location

Vrije Universiteit Medisch Centrum ( Site 0479)

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Tergooiziekenhuizen ( Site 0466)

Hilversum, North Holland, 1213 XZ, Netherlands

Location

Spaarne Ziekenhuis ( Site 0473)

Hoofddorp, North Holland, 2134TM, Netherlands

Location

Ziekenhuisgroep Twente ( Site 0469)

Hengelo, Overijssel, 7555 DL, Netherlands

Location

Haaglanden MC - locatie Antoniushove ( Site 0471)

Leidschendam, South Holland, 2501 ck, Netherlands

Location

Franciscus Gasthuis en Vlietland ( Site 0489)

Schiedam, South Holland, 3118 JH, Netherlands

Location

Tauranga Hospital ( Site 0215)

Tauranga, Bay of Plenty, 3112, New Zealand

Location

Canterbury Regional Cancer & Blood Service ( Site 0195)

Christchurch, Canterbury, 8011, New Zealand

Location

Auckland City Hospital ( Site 0193)

Auckland, 1023, New Zealand

Location

Przychodnia Lekarska Komed ( Site 0628)

Konin, Greater Poland Voivodeship, 62-500, Poland

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0636)

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

Location

Clinical Best Solutions ( Site 0622)

Warsaw, Masovian Voivodeship, 02-793, Poland

Location

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0624)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Salve Medica SP ( Site 0686)

Lodz, Łódź Voivodeship, 91-211, Poland

Location

Provita Prolife Centrum Medyczne ( Site 0630)

Tomaszów Mazowiecki, Łódź Voivodeship, 97-200, Poland

Location

Puerto Rico Medical Research Center LLC ( Site 1122)

San Juan, 00918, Puerto Rico

Location

FDI Clinical Research ( Site 1121)

San Juan, 00927, Puerto Rico

Location

Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)

Chelyabinsk, Chelyabinsk Oblast, 454087, Russia

Location

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)

Krasnoyarsk, Krasnoyarsk Krai, 660133, Russia

Location

State Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital" ( Site 0588)

Gatchina, Leningradskaya Oblast', 188300, Russia

Location

Russian Scientific Center of Roentgenoradiology ( Site 0559)

Moscow, Moscow, 117485, Russia

Location

Central Clinical Hospital with Polyclinic ( Site 0562)

Moscow, Moscow, 121359, Russia

Location

Omsk Clinical Oncology Dispensary ( Site 0568)

Omsk, Omsk Oblast, 644013, Russia

Location

SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)

Samara, Samara Oblast, 443031, Russia

Location

Clinical Research Center of specialized types medical care-Oncology ( Site 0570)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)

Tomsk, Tomsk Oblast, 634050, Russia

Location

National Cancer Center ( Site 0174)

Goyang-si, Kyonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital ( Site 0175)

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

Location

Asan Medical Center ( Site 0176)

Songpagu, Seoul, 05505, South Korea

Location

Seoul National University Hospital ( Site 0171)

Seoul, 03080, South Korea

Location

Samsung Medical Center ( Site 0172)

Seoul, 06351, South Korea

Location

Instituto Catalan de Oncologia - ICO ( Site 0330)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Parc Tauli ( Site 0335)

Sabadell, Barcelona, 08208, Spain

Location

Institut Català d'Oncologia (ICO) - Girona ( Site 0321)

Girona, Gerona, 17007, Spain

Location

Instituto Valenciano de Oncologia ( Site 0331)

Valencia, Valenciana, Comunitat, 46009, Spain

Location

Hospital del Mar ( Site 0333)

Barcelona, 08003, Spain

Location

Hospital Provincial San Pedro Alcantara ( Site 0326)

Cáceres, 10003, Spain

Location

Hospital Universitario Gregorio Maranon ( Site 0327)

Madrid, 28007, Spain

Location

MD Anderson Cancer Center Madrid ( Site 0332)

Madrid, 28033, Spain

Location

Hospital Clinico San Carlos ( Site 0324)

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro ( Site 0322)

Madrid, 28050, Spain

Location

Hospital Quiron Madrid ( Site 0325)

Madrid, 28223, Spain

Location

Hospital Universitario Virgen de la Victoria ( Site 0337)

Málaga, 29016, Spain

Location

Hospital Virgen del Rocio ( Site 0329)

Seville, 41013, Spain

Location

National Cheng Kung University Hospital ( Site 0134)

Tainen, Tainan, 704, Taiwan

Location

China Medical University Hospital ( Site 0132)

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital ( Site 0133)

Taichung, 407, Taiwan

Location

National Taiwan University Hospital ( Site 0131)

Taipei, 10048, Taiwan

Location

Taipei Veterans General Hospital ( Site 0135)

Taipei, 11217, Taiwan

Location

Ege University Medicine of Faculty ( Site 0661)

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Baskent University Dr. Turgut Noyan Research and Training Center-ONCCOLOGY ( Site 0618)

Adana, 01250, Turkey (Türkiye)

Location

Ankara University Hospital Cebeci ( Site 0613)

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Universitesi-oncology hospital ( Site 0615)

Ankara, 06230, Turkey (Türkiye)

Location

Ankara City Hospital-Medical Oncology ( Site 0616)

Ankara, 06800, Turkey (Türkiye)

Location

T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 0620)

Istanbul, 34440, Turkey (Türkiye)

Location

Acıbadem Maslak Hastanesi ( Site 0660)

Istanbul, 34457, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0619)

Istanbul, 34722, Turkey (Türkiye)

Location

Cherkasy Regional Oncology Dispensary ( Site 1203)

Cherkassy, Cherkasy Oblast, 18009, Ukraine

Location

Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 1205)

Dnipro, Dnipropetrovsk Oblast, 49005, Ukraine

Location

Dnepropetrovsk Regional Clinical Oncology Hospital-Clinical oncological dispensary ( Site 1201)

Dnipropetrovsk, Dnipropetrovsk Oblast, 49055, Ukraine

Location

Ivano-Frankivsk Regional Hospital-Urology department ( Site 1208)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76008, Ukraine

Location

Communal Non-Commercial Enterprise ""Prykarpatski Clinical Oncological Center"" of Ivano-Frankivsk R ( Site 1209)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

Location

CNPE Regional Center of Oncology-oncourology department ( Site 1202)

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

LISOD - Israeli Oncological Hospital ""MedX-ray Internationa-Department of Clinical and Scientific ( Site 1207)

Kiev, Kyivska Oblast, 08720, Ukraine

Location

Municipal non-profit enterprise Kyiv City Clinical Oncology -Oncourology department ( Site 1204)

Kyiv, Kyivska Oblast, 03115, Ukraine

Location

University Hospitals Bristol NHS Foundation Trust ( Site 0530)

Bristol, Bristol, City of, BS2 8ED, United Kingdom

Location

Cambridge University Hospitals NHS Trust ( Site 0540)

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Torbay Hospital ( Site 0532)

Torquay, Devon, TQ2 7AA, United Kingdom

Location

University College London Hospitals NHS Foundation Trust ( Site 0482)

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

Location

Western General Hospital ( Site 0531)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

Royal Marsden Hospital (Sutton) ( Site 0526)

London, Surrey, SM3 5PT, United Kingdom

Location

Musgrove Park Hospital ( Site 0537)

Taunton, Worcestershire, TA1 5DA, United Kingdom

Location

Mount Vernon Cancer Centre ( Site 0536)

Northwood, HA6 2RN, United Kingdom

Location

Related Publications (2)

• Graff JN, Burotto M, Fong PC, Pook DW, Zurawski B, Manneh Kopp R, Salinas J, Bylow KA, Kramer G, Ratta R, Kwiatkowski M, Retz M, Kwak C, Arranz Arija JA, Gurney H, Matsubara N, Villanueva L, Todenhofer T, Liang LW, Todoric J, Imai K, Stenzl A; KEYNOTE-641 Investigators. Pembrolizumab plus enzalutamide versus placebo plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer: the randomized, double-blind, phase III KEYNOTE-641 study. Ann Oncol. 2025 Aug;36(8):976-987. doi: 10.1016/j.annonc.2025.05.007. Epub 2025 May 16.

  PMID: 40383193 RESULT

• Graff JN, Liang LW, Kim J, Stenzl A. KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Future Oncol. 2021 Aug;17(23):3017-3026. doi: 10.2217/fon-2020-1008. Epub 2021 May 28.

  PMID: 34044584 DERIVED

Related Links

• Merck Oncology Clinical Trial Information
• Plain Language Summary

MeSH Terms

Conditions

Prostatic Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; enzalutamide; Saline Solution

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study became unblinded in February 2023.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: July 28, 2019
• Primary Completion: December 12, 2022
• Study Completion: May 29, 2026
• Last Updated: July 18, 2025
• Results First Posted: December 20, 2023

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

IL (10); US (28); AU (2); KR (5); ES (13); GB (8); CA (12); IT (14); CL (6); IE (3); JP (25); RU (10); AR (13); CZ (3); NZ (3); PL (6); PR (2); BR (8); TW (5); HU (4); TU (8); NL (11); UA (8); BU (3); FR (18); DE (13); CO (8)