Prostatic NeoplasmsPhase 3NCT03834493
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)
A Phase 3 study testing Pembrolizumab and Enzalutamide in people with Prostatic Neoplasms, run by Merck Sharp & Dohme LLC at 259 sites in 28 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Pembrolizumab and Enzalutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,244 participants
- Where
- 259 sitesin 28 countries
- Study dates
- 28 Jul 2019to 8 Jun 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
- Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
- 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 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 bradycardia (heart rate of <50 beats per minute) on the screening electrocardiogram (ECG)
- Has history of prostate cancer progression on ketoconazole
- Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate
- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
- Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
- Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization
- Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization
- Has received a live or live attenuated vaccine within 30 days prior to randomization
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
- Has a "superscan" bone scan
- Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of enzalutamide
- Has had an allogenic tissue/solid organ transplant
Trial locations and contacts
259 sites in 28 countries.
259 sites in 28 countries
United States28 sites
Georgia Cancer Center at Augusta University ( Site 0026)
Augusta, Georgia, 30912
University of Colorado Cancer Center ( Site 0022)
Aurora, Colorado, 80045
St. Vincent Frontier Cancer Center ( Site 0016)
Billings, Montana, 59102
Gabrail Cancer Center-Research ( Site 0096)
Canton, Ohio, 44718
Mount Sinai Hospital ( Site 0042)
Chicago, Illinois, 60608
Tri-State Urologic Services PSC, Inc. ( Site 0094)
Cincinnati, Ohio, 45212
University Hospitals Cleveland Medical Center ( Site 0036)
Cleveland, Ohio, 44106
Inova Schar Cancer Institute ( Site 0006)
Fairfax, Virginia, 22031
Providence Medical Foundation-Oncology ( Site 0069)
Fullerton, California, 92835
Cancer & Hematology Centers of Western Michigan ( Site 0013)
Grand Rapids, Michigan, 49503
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
Hackensack, New Jersey, 07601
Comprehensive Cancer Centers of Nevada ( Site 0092)
Las Vegas, Nevada, 89169
UCLA Hematology/Oncology - Santa Monica ( Site 0081)
Los Angeles, California, 90404
Methodist Hospitals. ( Site 0008)
Merrillville, Indiana, 46410
Froedtert Hospital & the Medical College of Wisconsin ( Site 0045)
Milwaukee, Wisconsin, 53226
University of South Alabama, Mitchell Cancer Institute ( Site 0065)
Mobile, Alabama, 36604
Carolina Urologic Research Center ( Site 0070)
Myrtle Beach, South Carolina, 29572
Smilow Cancer Hospital at Yale New Haven ( Site 0038)
New Haven, Connecticut, 06513
Tulane Cancer Center ( Site 0066)
New Orleans, Louisiana, 70112
Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0034)
Omaha, Nebraska, 68130
Oregon Health Science University ( Site 0031)
Portland, Oregon, 97239
Virginia Cancer Institute ( Site 0052)
Richmond, Virginia, 23230
Blue Ridge Cancer Care ( Site 0086)
Roanoke, Virginia, 24014
W. G. Bill Hefner VA Medical Center ( Site 0029)
Salisbury, North Carolina, 28144
Associated Medical Professionals of NY ( Site 0060)
Syracuse, New York, 13210
Moffitt Cancer Center ( Site 0080)
Tampa, Florida, 33612
Munson Medical Center ( Site 0030)
Traverse City, Michigan, 49684
University of Massachusetts Worcester ( Site 0053)
Worcester, Massachusetts, 01655
Japan25 sites
Chiba Cancer Center ( Site 0704)
Chiba, 260-8717
Kyushu University Hospital ( Site 0718)
Fukuoka, 812-8582
Hakodate Goryoukaku Hospital ( Site 0739)
Hakodate, Hokkaido, 040-8611
Hamamatsu University Hospital ( Site 0720)
Hamamatsu, Shizuoka, 431-3192
Saitama Medical University International Medical Center ( Site 0708)
Hidaka, Saitama, 350-1298
Hiroshima Prefectural Hospital ( Site 0748)
Hiroshima, 734-8530
Iizuka Hospital ( Site 0744)
Iizuka, Fukuoka, 820-8505
Kanazawa University Hospital ( Site 0701)
Kanazawa, Ishikawa-ken, 920-8641
Nara Medical University Hospital ( Site 0715)
Kashihara, Nara, 634-8522
National Cancer Center Hospital East ( Site 0702)
Kashiwa, Chiba, 2778577
Saitama Medical Center ( Site 0743)
Kawagoe, Saitama, 350-8550
Dokkyo Medical University Saitama Medical Center ( Site 0707)
Koshigaya, Saitama, 343-8555
National Hospital Organization Shikoku Cancer Center ( Site 0716)
Matsuyama, Ehime, 791-0280
University of Miyazaki Hospital ( Site 0721)
Miyazaki, 889-1692
Nagasaki University Hospital ( Site 0719)
Nagasaki, 852-8510
Miyagi Cancer Center ( Site 0747)
Natori-shi, Miyagi, 981-1293
Kitasato University Hospital ( Site 0705)
Sagamihara, Kanagawa, 252-0375
Toho University Sakura Medical Center ( Site 0703)
Sakura, Chiba, 285-8741
Kindai University Hospital ( Site 0714)
Sayama, Osaka, 589-8511
The University of Osaka Hospital ( Site 0713)
Suita, Osaka, 565-0871
Toranomon Hospital ( Site 0711)
Tokyo, 105-8470
Nippon Medical School Hospital ( Site 0709)
Tokyo, 113-8603
Keio University Hospital ( Site 0710)
Tokyo, 160-8582
Yamaguchi University Hospital ( Site 0717)
Ube, Yamaguchi, 755-8505
Yokohama City University Medical Center ( Site 0706)
Yokohama, Kanagawa, 232-0024
France18 sites
CHU Amiens Picardie Site Sud Amiens ( Site 0438)
Amiens, Somme, 80000
Institut Sainte Catherine ( Site 0447)
Avignon, Vaucluse, 84918
CHU Jean Minjoz ( Site 0423)
Besançon, Doubs, 25000
Institut Bergonie ( Site 0421)
Bordeaux, Gironde, 33076
CHU de Brest -Site Hopital Morvan ( Site 0441)
Brest, Brittany Region, 29200
Centre Jean Perrin ( Site 0434)
Clermont-Ferrand, Auvergne, 63011
Institut Regional du Cancer de Montpellier - ICM ( Site 0443)
Montpellier, Herault, 34298
Centre D Oncologie de Gentilly ( Site 0432)
Nancy, Meurthe-et-Moselle, 54000
Centre Hospitalier Regional du Orleans ( Site 0430)
Orléans, Loiret, 45100
Institut Mutualiste Montsouris ( Site 0446)
Paris, 75014
C.H.U. Lyon Sud ( Site 0436)
Pierre-Bénite, Rhone, 69310
Institut De Cancerologie De L Ouest ( Site 0448)
Saint-Herblain, Loire-Atlantique, 44805
C.H. de Saint Quentin ( Site 0481)
Saint-Quentin, Aisne, 02321
Clinique Sainte Anne ( Site 0431)
Strasbourg, Bas-Rhin, 67000
Hopital Foch ( Site 0428)
Suresnes, Hauts-de-Seine, 92150
Institut Claudius Regaud IUCT Oncopole ( Site 0418)
Toulouse, Haute-Garonne, 31059
Centre Hospitalier de Valenciennes ( Site 0439)
Valenciennes, Nord, 59300
Institut Gustave Roussy ( Site 0416)
Villejuif, Val-de-Marne, 94800
Italy14 sites
Medical Oncology Ospedale San Donato ( Site 0461)
Arezzo, 52100
Centro Di Riferimento Oncologico ( Site 0800)
Aviano, Pordenone, 33081
Ospedale Policlinico S. Orsola-Malpighi ( Site 0453)
Bologna, 40138
Azienda Ospedaliera Cannizzaro ( Site 0458)
Catania, 95126
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 0464)
Meldola, Emilia-Romagna, 47014
A.O. Universitaria di Modena ( Site 0454)
Modena, Emilia-Romagna, 41124
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0462)
Naples, 80131
Presidio Ospedaliero S. Maria Delle Grazie-U.O.C. ONCOLOGIA ( Site 0802)
Pozzuoli, Napoli, 80078
Azienda Ospedaliera San Camillo Forlanini ( Site 0455)
Roma, 00152
Fondazione Policlinico Universitario Agostino Gemelli ( Site 0801)
Roma, 00168
Istituto Clinico Humanitas Research Hospital ( Site 0452)
Rozzano, Lombardy, 20089
Azienda Ospedaliera Santa Maria Terni ( Site 0456)
Terni, 05100
Az. Osp. Univ. Sta Maria della Misericordia di Udine ( Site 0460)
Udine, 33100
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0465)
Verona, Veneto, 37134
Argentina13 sites
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
Berazategui, Buenos Aires, B1884BBF
Centro de Diagnostico Urologico ( Site 1008)
Buenos Aires, Buenos Aires F.D., C1120AAT
Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)
Buenos Aires, C1012AAR
Hospital Aleman ( Site 1004)
Buenos Aires, C1118AAT
Centro Medico Dra De Salvo ( Site 1018)
Buenos Aires, C1426ABP
Organizacion Medica de Investigacion ( Site 1019)
CABA, Buenos Aires, C1015ABO
Instituto Medico Alexander Fleming ( Site 1010)
Ciudad Autonoma de Buenos Aires., Buenos Aires, C1426ANZ
CEMAIC ( Site 1014)
Córdoba, X5008HHW
Centro Oncologico Riojano Integral ( Site 1005)
La Rioja, F5300COE
Instituto de Investigaciones Clinicas ( Site 1000)
Mar del Plata, Buenos Aires, B7600FZO
Centro Oncologico de Integracion Regional. COIR ( Site 1007)
Mendoza, M5500AYB
Sanatorio Parque ( Site 1002)
Rosario, Santa Fe Province, S2000DSV
Instituto de Oncologia de Rosario ( Site 1015)
Rosario, Santa Fe Province, S2000KZE
Germany13 sites
Uniklinik RWTH Aachen ( Site 0308)
Aachen, North Rhine-Westphalia, 52074
Charite Universitaetsmedizin Berlin ( Site 0301)
Berlin, 10117
Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Universitaetsklinikum Goettingen ( Site 0345)
Göttingen, Lower Saxony, 37075
Universitaetsklinikum des Saarlandes ( Site 0348)
Homburg, Saarland, 66421
Universitaetsklinikum Jena ( Site 0305)
Jena, Thuringia, 07747
Universitaetsklinikum Schleswig Holstein. ( Site 0346)
Lübeck, Schleswig-Holstein, 23538
Klinikum Rechts der Isar ( Site 0300)
Munich, Bavaria, 81675
Universitaetsklinikum Muenster ( Site 0320)
Münster, North Rhine-Westphalia, 48149
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
Nuremberg, Bavaria, 90419
Studienpraxis Urologie ( Site 0309)
Nürtingen, Baden-Wurttemberg, 72622
Krankenhaus der Barmherzigen Brueder Trier ( Site 0310)
Trier, Rhineland-Palatinate, 54292
Universitaetsklinik fuer Urologie ( Site 0307)
Tübingen, Baden-Wurttemberg, 72076
Spain13 sites
Hospital del Mar ( Site 0333)
Barcelona, 08003
Hospital Provincial San Pedro Alcantara ( Site 0326)
Cáceres, 10003
Institut Català d'Oncologia (ICO) - Girona ( Site 0321)
Girona, Gerona, 17007
Instituto Catalan de Oncologia - ICO ( Site 0330)
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Gregorio Maranon ( Site 0327)
Madrid, 28007
MD Anderson Cancer Center Madrid ( Site 0332)
Madrid, 28033
Hospital Clinico San Carlos ( Site 0324)
Madrid, 28040
Hospital Universitario HM Sanchinarro ( Site 0322)
Madrid, 28050
Hospital Quiron Madrid ( Site 0325)
Madrid, 28223
Hospital Universitario Virgen de la Victoria ( Site 0337)
Málaga, 29016
Hospital Parc Tauli ( Site 0335)
Sabadell, Barcelona, 08208
Hospital Virgen del Rocio ( Site 0329)
Seville, 41013
Instituto Valenciano de Oncologia ( Site 0331)
Valencia, Valenciana, Comunitat, 46009
Canada12 sites
Health Sciences North ( Site 0122)
Greater Sudbury, Ontario, P3E 5J1
CISSS de la Monteregie-Centre ( Site 0119)
Greenfield Park, Quebec, J4V 2H1
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)
Hamilton, Ontario, L8V 5C2
Grand River Hospital ( Site 0120)
Kitchener, Ontario, N2G 1G3
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)
Montreal, Quebec, H2X 3E4
Lakeridge Health ( Site 0117)
Oshawa, Ontario, L1G 2B9
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0103)
Québec, Quebec, G1J 1Z4
CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)
Rimouski, Quebec, G5L 5T1
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)
Sherbrooke, Quebec, J1H 5N4
Sunnybrook Research Institute ( Site 0108)
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre ( Site 0107)
Toronto, Ontario, M5G 2M9
BC Cancer Victoria-Clinical Trials Unit ( Site 0111)
Victoria, British Columbia, V8R 6V5
Netherlands11 sites
Noordwest Ziekenhuisgroep NWZ ( Site 0468)
Alkmaar, North Holland, 1815 JD
Vrije Universiteit Medisch Centrum ( Site 0479)
Amsterdam, North Holland, 1081 HV
Amphia Hospital Location Molengracht ( Site 0474)
Breda, North Brabant, 4818 CK
Catharina Ziekenhuis ( Site 0472)
Eindhoven, North Brabant, 5623 EJ
Ziekenhuisgroep Twente ( Site 0469)
Hengelo, Overijssel, 7555 DL
Tergooiziekenhuizen ( Site 0466)
Hilversum, North Holland, 1213 XZ
Spaarne Ziekenhuis ( Site 0473)
Hoofddorp, North Holland, 2134TM
Haaglanden MC - locatie Antoniushove ( Site 0471)
Leidschendam, South Holland, 2501 ck
Maastricht University Medical Centre ( Site 0467)
Maastricht, Limburg, 6229 HX
Radboud University Medical Center ( Site 0470)
Nijmegen, Gelderland, 6525 GA
Franciscus Gasthuis en Vlietland ( Site 0489)
Schiedam, South Holland, 3118 JH
Australia10 sites
Royal Adelaide Hospital ( Site 0154)
Adelaide, South Australia, 5000
Monash Medical Centre ( Site 0147)
Clayton, Victoria, 3168
St. Vincent's Hospital ( Site 0158)
Darlinghurst, New South Wales, 2010
Gallipoli Medical Research Ltd ( Site 0149)
Greenslopes, Queensland, 4120
St George Hospital ( Site 0157)
Kogarah, New South Wales, 2217
Macquarie University ( Site 0151)
Macquarie University, New South Wales, 2109
Fiona Stanley Hospital ( Site 0162)
Perth, Western Australia, 6150
Port Macquarie Base Hospital ( Site 0153)
Port Macquarie, New South Wales, 2444
Gold Coast University Hospital ( Site 0150)
Southport, Queensland, 4215
Calvary Mater Newcastle ( Site 0148)
Waratah, New South Wales, 2298
Israel10 sites
HaEmek Medical Center ( Site 0548)
Afula, 1834111
Assuta Ashdod Medical Center ( Site 0550)
Ashdod, 7747629
Soroka Medical Center ( Site 0549)
Beersheba, 8410101
Rambam Health Care Campus-Oncology Division ( Site 0543)
Haifa, 3109601
Hadassah Ein Kerem Medical Center ( Site 0546)
Jerusalem, 9112001
Meir Medical Center ( Site 0544)
Kfar Saba, 4428164
Rabin Medical Center ( Site 0545)
Petah Tikva, 4941492
Chaim Sheba Medical Center ( Site 0541)
Ramat Gan, 5262000
Sourasky Medical Center ( Site 0542)
Tel Aviv, 6423906
Yitzhak Shamir Medical Center. ( Site 0547)
Ẕerifin, 70300
Russia10 sites
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
Chelyabinsk, Chelyabinsk Oblast, 454087
State Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital" ( Site 0588)
Gatchina, Leningradskaya Oblast', 188300
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
Krasnoyarsk, Krasnoyarsk Krai, 660133
Russian Scientific Center of Roentgenoradiology ( Site 0559)
Moscow, Moscow, 117485
Central Clinical Hospital with Polyclinic ( Site 0562)
Moscow, Moscow, 121359
Omsk Clinical Oncology Dispensary ( Site 0568)
Omsk, Omsk Oblast, 644013
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
Saint Petersburg, Sankt-Peterburg, 197758
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
Saint Petersburg, Sankt-Peterburg, 197758
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
Samara, Samara Oblast, 443031
Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)
Tomsk, Tomsk Oblast, 634050
Brazil8 sites
Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1036)
Curitiba, Paraná, 81520-060
ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 1038)
Ijuí, Rio Grande do Sul, 98700-000
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)
Itajaí, Santa Catarina, 88301-215
Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1032)
Natal, Rio Grande do Norte, 59075-740
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital de Base de Sao Jose de Rio Preto ( Site 1022)
São José do Rio Preto, São Paulo, 15090-000
A.C. Camargo Cancer Center ( Site 1026)
São Paulo, 01509-900
Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1040)
São Paulo, 04014-002
Colombia8 sites
Biomelab S A S ( Site 1067)
Barranquilla, Atlántico, 080001
Clinica de la Costa S.A.S. ( Site 1073)
Barranquilla, Atlántico, 080020
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)
Bogotá, Bogota D.C., 110311
Clínica Imbanaco S.A.S ( Site 1064)
Cali, Valle del Cauca Department, 760042
Hemato Oncologos S.A. ( Site 1065)
Cali, Valle del Cauca Department, 760042
Hospital Pablo Tobon Uribe ( Site 1066)
Medellín, Antioquia, 050034
Oncomédica S.A.S ( Site 1057)
Montería, Departamento de Córdoba, 230002
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)
Valledupar, Cesar Department, 200001
Turkey (Türkiye)8 sites
Baskent University Dr. Turgut Noyan Research and Training Center-ONCCOLOGY ( Site 0618)
Adana, 01250
Ankara University Hospital Cebeci ( Site 0613)
Ankara, 06100
Hacettepe Universitesi-oncology hospital ( Site 0615)
Ankara, 06230
Ankara City Hospital-Medical Oncology ( Site 0616)
Ankara, 06800
Ege University Medicine of Faculty ( Site 0661)
Bornova, İzmir, 35100
T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training ( Site 0620)
Istanbul, 34440
Acıbadem Maslak Hastanesi ( Site 0660)
Istanbul, 34457
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0619)
Istanbul, 34722
Ukraine8 sites
Cherkasy Regional Oncology Dispensary ( Site 1203)
Cherkassy, Cherkasy Oblast, 18009
Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 1205)
Dnipro, Dnipropetrovsk Oblast, 49005
Dnepropetrovsk Regional Clinical Oncology Hospital-Clinical oncological dispensary ( Site 1201)
Dnipropetrovsk, Dnipropetrovsk Oblast, 49055
Ivano-Frankivsk Regional Hospital-Urology department ( Site 1208)
Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76008
Communal Non-Commercial Enterprise ""Prykarpatski Clinical Oncological Center"" of Ivano-Frankivsk R ( Site 1209)
Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018
CNPE Regional Center of Oncology-oncourology department ( Site 1202)
Kharkiv, Kharkiv Oblast, 61070
LISOD - Israeli Oncological Hospital ""MedX-ray Internationa-Department of Clinical and Scientific ( Site 1207)
Kiev, Kyivska Oblast, 08720
Municipal non-profit enterprise Kyiv City Clinical Oncology -Oncourology department ( Site 1204)
Kyiv, Kyivska Oblast, 03115
United Kingdom8 sites
University Hospitals Bristol NHS Foundation Trust ( Site 0530)
Bristol, Bristol, City of, BS2 8ED
Cambridge University Hospitals NHS Trust ( Site 0540)
Cambridge, Cambridgeshire, CB2 0QQ
Western General Hospital ( Site 0531)
Edinburgh, Midlothian, EH4 2XU
University College London Hospitals NHS Foundation Trust ( Site 0482)
London, London, City of, NW1 2PG
Royal Marsden Hospital (Sutton) ( Site 0526)
London, Surrey, SM3 5PT
Mount Vernon Cancer Centre ( Site 0536)
Northwood, HA6 2RN
Musgrove Park Hospital ( Site 0537)
Taunton, Worcestershire, TA1 5DA
Torbay Hospital ( Site 0532)
Torquay, Devon, TQ2 7AA
Chile6 sites
Fundacion Arturo Lopez Perez ( Site 1049)
Santiago, Region M. de Santiago, 7500921
Pontificia Universidad Catolica de Chile ( Site 1047)
Santiago, Region M. de Santiago, 8330024
Bradfordhill ( Site 1044)
Santiago, Region M. de Santiago, 8420383
Centro Investigación del Cáncer James Lind ( Site 1041)
Temuco, Araucania, 4800827
Rey y Oreilly Limitada ( Site 1048)
Temuco, Araucania, 4810148
Oncocentro ( Site 1045)
Viña del Mar, Valparaiso, 2520598
Poland6 sites
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0636)
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796
Przychodnia Lekarska Komed ( Site 0628)
Konin, Greater Poland Voivodeship, 62-500
Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0624)
Koszalin, West Pomeranian Voivodeship, 75-581
Salve Medica SP ( Site 0686)
Lodz, Łódź Voivodeship, 91-211
Provita Prolife Centrum Medyczne ( Site 0630)
Tomaszów Mazowiecki, Łódź Voivodeship, 97-200
Clinical Best Solutions ( Site 0622)
Warsaw, Masovian Voivodeship, 02-793
South Korea5 sites
National Cancer Center ( Site 0174)
Goyang-si, Kyonggi-do, 10408
Seoul National University Bundang Hospital ( Site 0175)
Seongnam-si, Kyonggi-do, 13620
Seoul National University Hospital ( Site 0171)
Seoul, 03080
Samsung Medical Center ( Site 0172)
Seoul, 06351
Asan Medical Center ( Site 0176)
Songpagu, Seoul, 05505
Taiwan5 sites
China Medical University Hospital ( Site 0132)
Taichung, 40447
Taichung Veterans General Hospital ( Site 0133)
Taichung, 407
National Cheng Kung University Hospital ( Site 0134)
Tainen, Tainan, 704
National Taiwan University Hospital ( Site 0131)
Taipei, 10048
Taipei Veterans General Hospital ( Site 0135)
Taipei, 11217
Hungary4 sites
Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 1325)
Budapest, Pest County, 1122
Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 1326)
Budapest, 1062
Petz Aladár Megyei Oktató Kórház-Onkológiai Osztály ( Site 1324)
Győr, Győr-Moson-Sopron, 9024
Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1321)
Kecskemét, Bács-Kiskun county, 6000
Bulgaria3 sites
MHAT Central Hospital ( Site 0503)
Plovdiv, 4000
Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0507)
Plovdiv, 4004
MHAT Serdika-Second Department of Medical Oncology ( Site 0505)
Sofia, Sofia (stolitsa), 1301
Czechia3 sites
Fakultni Nemocnice u sv. Anny v Brne-Onkologicko-chirurgicke oddeleni ( Site 1303)
Brno, Brno-mesto, 656 91
Nemocnice AGEL Novy Jicin a.s. ( Site 1304)
Nový Jičín, Novy Jicin, 741 01
Fakultni nemocnice Olomouc ( Site 1301)
Olomouc, Olomouc Region, 779 00
Ireland3 sites
Beaumont Hospital ( Site 0726)
Dublin, D09 V2N0
Tallaght University Hospital ( Site 0730)
Dublin, D24 NROA
Mid Western Cancer Centre ( Site 0728)
Limerick, V98F858
New Zealand3 sites
Auckland City Hospital ( Site 0193)
Auckland, 1023
Canterbury Regional Cancer & Blood Service ( Site 0195)
Christchurch, Canterbury, 8011
Tauranga Hospital ( Site 0215)
Tauranga, Bay of Plenty, 3112
Austria2 sites
Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)
Linz, Upper Austria, 4020
Medizinische Universität Wien ( Site 0375)
Vienna, 1090
Puerto Rico2 sites
Puerto Rico Medical Research Center LLC ( Site 1122)
San Juan, 00918
FDI Clinical Research ( Site 1121)
San Juan, 00927
About this study
Official title: A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-641)
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
- Being tested
- Pembrolizumab, Enzalutamide, Placebo
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- Prostatic Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called KEYTRUDA®, MK-3475
IV infusion
EnzalutamideDrug
Also called XTANDI®
Capsules/Tablets
PlaceboDrug
Also called Normal saline or dextrose infusion
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Enzalutamide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. The OS for all participants is presented.
Measured: 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.
Measured: 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)
TFST was defined as time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurs first. The TFST for all participants is presented.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Prostate-specific Antigen (PSA) Response Rate
PSA response rate was defined as percentage of participants in the analysis population who have a negative change (decrease) in PSA level of ≥50% measured twice ≥3 weeks apart. The analysis was performed on participants who had baseline PSA measurements.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Prostate-specific Antigen (PSA) Undetectable Rate
PSA undetectable rate was defined as percentage of participants in the analysis population with PSA <0.2 ng/mL during study treatment. The analysis was performed on participants who had baseline PSA measurements.
Measured: 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
OR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).
Measured: 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
DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for ≥6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Time to Prostate-specific Antigen (PSA) Progression
Time from randomization to PSA progression. PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review
Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score)
Time from randomization to pain progression. In this study, pain progression was assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores which are both assessed by participants daily for 7 consecutive days.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Time to First Symptomatic Skeletal-related Event (SSRE)
Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Number of Participants Who Experience an Adverse Event (AE)
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who experienced an AE is presented.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to 40 months (through database cut-off date of 12-Dec-2022)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2019
- Study start28 Jul 2019
- Primary completion12 Dec 2022
- Study completion8 Jun 2026
Why it stopped: The study stopped due to futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,244 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03834493
- Sponsor's protocol ID
- 3475-641
- Other IDs
- MK-3475-641, KEYNOTE-641, 195005, 2022-500785-10-00, U1111-1278-1151, 2018-004117-40, 2018
- Status last verified
- Aug 2026
- First submitted
- 6 Feb 2019
- Last updated
- 28 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 40383193Graff 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.
PubMed 34044584