Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)

A Phase 3, Randomized, Double-blind Study of Pembrolizumab (MK-3475) Plus Docetaxel Plus Prednisone Versus Placebo Plus Docetaxel Plus Prednisone in Participants With Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Progressed on a Next Generation Hormonal Agent (NHA) (KEYNOTE-921)

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and docetaxel in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but have progressed on or are intolerant to Next Generation Hormonal Agent (NHA).

There are two primary study hypotheses.

Hypothesis 1: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone with respect to Overall Survival (OS).

Hypothesis 2: The combination of pembrolizumab plus docetaxel plus prednisone is superior to placebo plus docetaxel plus prednisone 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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Docetaxel; Drug: Prednisone; Drug: Dexamethasone; Drug: Placebo

Detailed Description

With Amendment 6 (effective date: 29-Sep-2022), all participants will be unblinded and placebo treatment will be stopping. Participants who are deemed to be deriving clinical benefit from treatment may continue at the discretion of the investigator.

The global study for MK-3475-921 enrolled 1030 participants. Of the 1030 total participants enrolled in the global study, 21 were also enrolled in the China extension study for MK-3475-921 (NCT04907227).

• Study Type: Interventional
• Enrollment (Actual): 1030
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman ( Site 1004)
  • Buenos Aires, Argentina, C1426ANZ
    • Instituto Medico Alexander Fleming ( Site 1010)
  • Cordoba, Argentina, X5008HHW
    • CEMAIC ( Site 1014)
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, B1884BBF
      • Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • Instituto de Investigaciones Clinicas ( Site 1000)
  • Caba
    • Buenos Aires, Caba, Argentina, C1120AAT
      • Centro de Diagnostico Urologico ( Site 1008)
    • Buenos Aires, Caba, Argentina, C1280AEB
      • Hospital Britanico de Buenos Aires ( Site 1006)
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DSV
      • Sanatorio Parque ( Site 1002)
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital ( Site 0157)
    • Macquarie University, New South Wales, Australia, 2109
      • Macquarie University ( Site 0151)
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital ( Site 0153)
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle ( Site 0148)
  • Queensland
    • Redcliffe, Queensland, Australia, 4020
      • Redcliffe Hospital ( Site 0161)
    • Tugun, Queensland, Australia, 4224
      • John Flynn Hospital & Medical Centre ( Site 0164)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Hollywood Private Hospital ( Site 0163)
• Austria
  • Salzburg, Austria, 5020
    • SCRI-CCCIT GesmbH ( Site 0371)
  • Wien, Austria, 1090
    • Medizinische Universitaet Wien ( Site 0375)
  • Oberosterreich
    • Linz, Oberosterreich, Austria, 4020
      • Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universitat Graz ( Site 0374)
• Brazil
  • Sao Paulo, Brazil, 01509-900
    • A.C. Camargo Cancer Center ( Site 1026)
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • Hospital de Caridade de Ijui ( Site 1038)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
  • Santa Catarina
    • Itajai, Santa Catarina, Brazil, 88301-215
      • Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)
  • Sao Paulo
    • Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose de Rio Preto ( Site 1022)
• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0103)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority QEII-HSC ( Site 0114)
  • Ontario
    • Hamilton, Ontario, Canada, L8V5C2
      • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Hospital ( Site 0120)
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health ( Site 0117)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0108)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0107)
  • Quebec
    • Rimouski, Quebec, Canada, G5L 5T1
      • CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4780000
      • Centro Investigación del Cáncer James Lind ( Site 1041)
    • Temuco, Araucania, Chile, 4810148
      • Rey y Oreilly Limitada ( Site 1048)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez ( Site 1049)
    • Santiago, Region M. De Santiago, Chile, 8330032
      • Pontificia Universidad Catolica de Chile ( Site 1047)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Bradford Hill Centro de Investigaciones Clinicas ( Site 1044)
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2540488
      • Centro de Investigaciones Clinicas Vina del Mar ( Site 1042)
• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital ( Site 1303)
    • Beijing, Beijing, China, 100071
      • The Fifth Medical Center of PLA General Hospital ( Site 1307)
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital ( Site 1305)
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University ( Site 1319)
  • Guangdong
    • Guangzhou, Guangdong, China, 510220
      • Sun Yat Sen Memorial Hospital ( Site 1323)
    • Guangzhou, Guangdong, China, 510230
      • The First Affiliated Hospital of Guangzhou Medical University ( Site 1330)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital ( Site 1326)
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital ( Site 1321)
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital ( Site 1329)
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 1320)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital ( Site 1312)
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center ( Site 1300)
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University ( Site 1301)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309)
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital ( Site 1310)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe ( Site 1066)
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080002
      • Biomelab S A S ( Site 1067)
    • Barranquilla, Atlantico, Colombia, 080020
      • Clinica de la Costa Ltda. ( Site 1073)
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)
  • Cordoba
    • Monteria, Cordoba, Colombia, 230002
      • Oncomedica S.A. ( Site 1057)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 110321
      • Instituto Nacional de Cancerologia E.S.E ( Site 1061)
    • Bogota, Distrito Capital De Bogota, Colombia, 111321
      • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)
  • Risaralda
    • Pereira, Risaralda, Colombia, 660001
      • Oncologos del Occidente S.A. ( Site 1072)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760042
      • Centro Medico Imbanaco de Cali S.A ( Site 1064)
    • Cali, Valle Del Cauca, Colombia, 760042
      • Hemato Oncologos S.A. ( Site 1065)
• France
  • Paris, France, 75014
    • Institut Mutualiste Montsouris ( Site 0446)
  • Aisne
    • Saint Quentin, Aisne, France, 02321
      • C.H. de Saint Quentin ( Site 0481)
  • Alsace
    • Strasbourg, Alsace, France, 67000
      • Clinique Sainte Anne ( Site 0431)
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63011
      • Centre Jean Perrin ( Site 0434)
    • Lyon, Auvergne, France, 69373
      • Centre Leon Berard ( Site 0422)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13009
      • Institut Paoli Calmettes. ( Site 0419)
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU Jean Minjoz ( Site 0423)
  • Finistere
    • Brest, Finistere, France, 29200
      • CHU de Brest -Site Hopital Morvan ( Site 0441)
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Institut Bergonie ( Site 0421)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud IUCT Oncopole ( Site 0418)
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • Hopital Foch ( Site 0428)
  • Loire-Atlantique
    • Saint Herblain, Loire-Atlantique, France, 44805
      • Institut De Cancerologie De L Ouest ( Site 0448)
  • Loiret
    • Orleans, Loiret, France, 45100
      • Centre Hospitalier Regional du Orleans ( Site 0430)
  • Meurthe-et-Moselle
    • Nancy, Meurthe-et-Moselle, France, 54100
      • Centre D Oncologie de Gentilly ( Site 0432)
  • Rhone
    • Pierre Benite, Rhone, France, 69310
      • C.H.U. Lyon Sud ( Site 0436)
  • Somme
    • Amiens, Somme, France, 80000
      • CHU Amiens Picardie Site Sud Amiens ( Site 0438)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94800
      • Institut Gustave Roussy ( Site 0416)
  • Vaucluse
    • Avignon, Vaucluse, France, 84000
      • Institut Sainte Catherine ( Site 0447)
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin ( Site 0301)
  • Baden-Wurttemberg
    • Freiburg, Baden-Wurttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Universitaetsklinikum in Mannheim ( Site 0314)
    • Nuertingen, Baden-Wurttemberg, Germany, 72622
      • Studienpraxis Urologie ( Site 0309)
    • Tuebingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinik fuer Urologie ( Site 0307)
  • Bayern
    • Muenchen, Bayern, Germany, 81675
      • Klinikum Rechts der Isar ( Site 0300)
    • Nuernberg, Bayern, Germany, 90419
      • Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
    • Wuerzburg, Bayern, Germany, 97080
      • Universitaetsklinikum Wuerzburg ( Site 0302)
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, 37075
      • Universitaetsklinikum Goettingen ( Site 0345)
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Uniklinik RWTH Aachen ( Site 0308)
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitaetsklinikum des Saarlandes ( Site 0348)
  • Thuringen
    • Jena, Thuringen, Germany, 07747
      • Universitaetsklinikum Jena ( Site 0305)
• Ireland
  • Cork, Ireland, T12 YE02
    • Cork University Hospital ( Site 0727)
  • Dublin, Ireland, D24 NROA
    • Tallaght University Hospital ( Site 0730)
  • Limerick, Ireland
    • Mid Western Cancer Centre ( Site 0728)
• Israel
  • Beer Sheva, Israel, 8410101
    • Soroka Medical Center ( Site 0548)
  • Beer Yaakov-Zerifin, Israel, 7030001
    • Assaf Harofeh MC ( Site 0547)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0543)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 0546)
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center ( Site 0544)
  • Petach-Tikwa, Israel, 4941492
    • Rabin Medical Center ( Site 0545)
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center ( Site 0541)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0542)
• Italy
  • Catania, Italy, 95126
    • Azienda Ospedaliera Cannizzaro ( Site 0458)
  • Modena, Italy, 41100
    • A.O. Universitaria di Modena ( Site 0454)
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0457)
  • Roma, Italy, 00152
    • Azienda Ospedaliera San Camillo Forlanini ( Site 0455)
  • Terni, Italy, 05100
    • Azienda Ospedaliera Santa Maria Terni ( Site 0456)
  • Trento, Italy, 38122
    • Presidio Ospedaliero Santa Chiara ( Site 0451)
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas Research Hospital ( Site 0452)
• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center ( Site 0704)
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0718)
  • Miyazaki, Japan, 889-1692
    • University of Miyazaki Hospital ( Site 0721)
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital ( Site 0719)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 0711)
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital ( Site 0709)
  • Tokyo, Japan, 160-8582
    • Keio University Hospital ( Site 0710)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0702)
    • Sakura, Chiba, Japan, 285-8741
      • Toho University Sakura Medical Center ( Site 0703)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 0716)
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital ( Site 0701)
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Kitasato University Hospital ( Site 0705)
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center ( Site 0706)
  • Nara
    • Kashihara, Nara, Japan, 634-8522
      • Nara Medical University Hospital ( Site 0715)
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0714)
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 0713)
  • Saitama
    • Hidaka, Saitama, Japan, 1932
      • Saitama Medical University International Medical Center ( Site 0708)
    • Koshigaya, Saitama, Japan, 343-8555
      • Dokkyo Medical University Saitama Medical Center ( Site 0707)
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital ( Site 0720)
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Hospital ( Site 0717)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 0171)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 0176)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 0172)
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, Korea, Republic of, 10408
      • National Cancer Center ( Site 0174)
    • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 0175)
• Netherlands
  • Fryslan
    • Leeuwarden, Fryslan, Netherlands, 8934 AD
      • Medisch Centrum Leeuwarden ( Site 0477)
  • Gelderland
    • Ede, Gelderland, Netherlands, 6746 RP
      • Ziekenhuis Gelderse Vallei ( Site 0485)
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University Medical Center ( Site 0470)
  • Limburg
    • Venlo, Limburg, Netherlands, 5912 BL
      • VieCuri Medisch Centrum ( Site 0487)
  • Noord-Brabant
    • Den Bosch, Noord-Brabant, Netherlands, 5223 GZ
      • Jeroen Bosch Ziekenhuis ( Site 1200)
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Catharina Ziekenhuis ( Site 0472)
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066 CX
      • Antoni van Leeuwenhoek Ziekenhuis ( Site 0480)
    • Hilversum, Noord-Holland, Netherlands, 1213 XZ
      • Ziekenhuis Hilversum ( Site 0466)
  • Overijssel
    • Hengelo, Overijssel, Netherlands, 7555 DL
      • Ziekenhuisgroep Twente ( Site 0469)
  • Zuid-Holland
    • Delft, Zuid-Holland, Netherlands, 2625 AD
      • Reinier de Graaf Groep ( Site 0484)
    • Den Haag, Zuid-Holland, Netherlands, 2545 AA
      • Hagaziekenhuis ( Site 1201)
• Russian Federation
  • Chelyabinskaya Oblast
    • Chelyabinsk, Chelyabinskaya Oblast, Russian Federation, 454087
      • Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
  • Krasnoyarskiy Kray
    • Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133
      • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
  • Moskva
    • Moscow, Moskva, Russian Federation, 105077
      • SBIH City clinical hospital named after D.D. Pletniov ( Site 0575)
    • Moscow, Moskva, Russian Federation, 117485
      • Russian Scientific Center of Radiology ( Site 0559)
    • Moscow, Moskva, Russian Federation, 121359
      • Central Clinical Hospital with Polyclinic ( Site 0562)
    • Moscow, Moskva, Russian Federation, 125284
      • National Medical Research Radiological Center ( Site 0556)
  • Nizhegorodskaya Oblast
    • Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603074
      • Volga District Medical Center Federal Medical and Biological Agency ( Site 0572)
  • Omskaya Oblast
    • Omsk, Omskaya Oblast, Russian Federation, 644013
      • Omsk Clinical Oncology Dispensary ( Site 0568)
  • Samarskaya Oblast
    • Samara, Samarskaya Oblast, Russian Federation, 443031
      • SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • SPb SBHI City Clinical Oncological Dispensary ( Site 0571)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 188663
      • Leningrad Regional Oncology Center ( Site 0588)
  • Tomskaya Oblast
    • Tomsk, Tomskaya Oblast, Russian Federation, 634050
      • Tomsk National Research Medical Center of Russian Academy of Sciences ( Site 0579)
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar ( Site 0333)
  • Barcelona, Spain, 08036
    • Hospital Clinic ( Site 0323)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal ( Site 0328)
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos ( Site 0324)
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro ( Site 0322)
  • Malaga, Spain, 29016
    • Hospital Universitario Virgen de la Victoria ( Site 0337)
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocio ( Site 0329)
  • Barcelona
    • L Hospitalet De Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia - ICO ( Site 0330)
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Consorci Sanitari Parc Tauli ( Site 0335)
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla ( Site 0336)
  • Gerona
    • Girona, Gerona, Spain, 17007
      • Hospital Josep Trueta ( Site 0321)
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital ( Site 0132)
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital ( Site 0133)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 0131)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 0135)
  • Tainan
    • Tainen, Tainan, Taiwan, 704
      • National Cheng Kung University Hospital ( Site 0134)
• United Kingdom
  • Bristol, City Of
    • Bristol, Bristol, City Of, United Kingdom, BS2 8ED
      • University Hospitals Bristol NHS Foundation Trust ( Site 0530)
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Trust ( Site 0540)
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Torbay Hospital ( Site 0532)
  • England
    • Sheffield, England, United Kingdom, S10 2SJ
      • Weston Park Hospital ( Site 0539)
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden Hospital ( Site 0526)
  • Hertfordshire
    • Northwood, Hertfordshire, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre ( Site 0536)
  • London, City Of
    • London, London, City Of, United Kingdom, EC1A 7BE
      • Barts Cancer Institute ( Site 0483)
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • University of North Midlands NHS Foundation Trust ( Site 0527)
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama, Mitchell Cancer Institute ( Site 0065)
  • California
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare ( Site 0069)
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Comprehensive Cancer Center ( Site 0061)
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology Hematology Newport Beach ( Site 0093)
    • San Francisco, California, United States, 94158
      • University of California San Francisco ( Site 0023)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center ( Site 0022)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center ( Site 0038)
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center ( Site 0080)
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University ( Site 0026)
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center ( Site 0042)
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Methodist Hospital- Merriillville ( Site 0008)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute ( Site 0077)
    • Detroit, Michigan, United States, 48202-2608
      • Henry Ford Health System ( Site 0039)
    • Grand Rapids, Michigan, United States, 49503
      • Cancer & Hematology Centers of Western Michigan ( Site 0013)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 0057)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center ( Site 0016)
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists ( Site 0034)
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada ( Site 0092)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
  • New York
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of NY ( Site 0060)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center ( Site 0010)
    • Salisbury, North Carolina, United States, 28144
      • W. G. Bill Hefner VA Medical Center ( Site 0029)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center ( Site 0036)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University ( Site 0031)
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center ( Site 0070)
  • Virginia
    • Fairfax, Virginia, United States, 22031-4867
      • Inova Schar Cancer Institute ( Site 0006)
    • Richmond, Virginia, United States, 23230
      • Virginia Cancer Institute ( Site 0052)
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care ( Site 0086)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• 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 screening
• 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 received prior treatment with one (but not more than one) NHA (eg, abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC) and either a) progressed through treatment OR b) has become intolerant of the drug
• 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 120 days after the last dose of pembrolizumab or for at least 180 days after the last dose of docetaxel (whichever is longer): Refrain from donating sperm PLUS Use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
• Participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
• 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

Exclusion Criteria:

• 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 current pneumonitis
• Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)
• Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization or who has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to mAbs
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto) prior to randomization
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
• Has hypersensitivity to docetaxel or polysorbate 80
• Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Has received prior targeted small molecule therapy or abiraterone acetate, enzalutamide, apalutamide, or darolutamide within 4 weeks prior to the first dose of study treatment, or has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to a previously administered agent
• Has received prior radiotherapy to within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
• Has received a live vaccine within 30 days prior to randomization
• Has received treatment with 5α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to randomization
• Has received prior treatment with ketoconazole for prostate cancer
• 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 120 days after the last dose of study treatment
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab+Docetaxel; Participants receive pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m^2 by IV infusion Q3W for a maximum of 10 cycles (approximately 7 months). Participants also receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each docetaxel cycle.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®; Drug: Docetaxel; IV infusion; Other Names: TAXOTERE®; Drug: Prednisone; Oral tablets; Drug: Dexamethasone; Oral tablets; Other Names: DECADRON®
Placebo Comparator: Placebo+Docetaxel; Participants receive placebo by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to a maximum of 35 cycles (approximately 2 years) PLUS docetaxel 75 mg/m^2 by IV infusion Q3W for a maximum of 10 cycles (approximately 7 months). Participants also receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours, and 1 hour prior to docetaxel administration and prednisone 5 mg by oral tablets twice daily during each docetaxel cycle.	Drug: Docetaxel; IV infusion; Other Names: TAXOTERE®; Drug: Prednisone; Oral tablets; Drug: Dexamethasone; Oral tablets; Other Names: DECADRON®; Drug: Placebo; IV infusion; Other Names: Normal saline or dextrose infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 36.5 months
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	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 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 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)	TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit (Kaplan-Meier) method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received.	Up to approximately 28 months
Prostate-specific Antigen (PSA) Response Rate	The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements.	Up to 36.5 months
Objective Response Rate (ORR) 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	ORR 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).	Up to 36.5 months
Duration of Response (DOR) 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	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.	Up to 36.5 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 Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score	TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF and by the AQA score. Pain progression was defined as: For participants asymptomatic at baseline: a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain; For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids:, a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits. TTPP was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.	Up to 36.5 months
Time to First Symptomatic Skeletal-related Event (SSRE)	SSRE was the time from randomization to the first symptomatic skeletal-related event defined as: Use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms; Occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral); Occurrence of spinal cord compression; Tumor-related orthopedic surgical intervention, whichever occurs first. The SSRE was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.	Up to 36.5 months
Time to Prostate-specific Antigen (PSA) Progression	The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of: ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR; ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline Time to PSA progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without PSA progression were censored at the last evaluable assessment.	Up to 36.5 months
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) as Assessed by Blinded Independent Central Review (BICR)	The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.	Up to 36.5 months
Number of Participants Who Experienced an Adverse Event (AE)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented.	Up to approximately 30 months
Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented.	Up to approximately 27 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Petrylak DP, Ratta R, Gafanov R, Facchini G, Piulats JM, Kramer G, Flaig TW, Chandana SR, Li B, Burgents J, Fizazi K. KEYNOTE-921: Phase III study of pembrolizumab plus docetaxel for metastatic castration-resistant prostate cancer. Future Oncol. 2021 Sep;17(25):3291-3299. doi: 10.2217/fon-2020-1133. Epub 2021 Jun 8.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): July 18, 2023

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Programmed Cell Death 1 (PD 1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL 1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL 2, PD-L2)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Docetaxel; Dexamethasone; Pembrolizumab; Prednisone
• Other Study ID Numbers: 3475-921; MK-3475-921 (Other Identifier: Merck); KEYNOTE-921 (Other Identifier: Merck); JAPAC-CTI (Registry Identifier: 194831); 2018-004116-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No