Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)

November 16, 2023 updated by: Merck Sharp & Dohme LLC

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)

This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus Androgen Deprivation Therapy (ADT) versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of 19-JAN-2023, the study was unblinded and all study participants stopped ongoing treatment with pembrolizumab/placebo and will continue to receive Standard of Care treatment until meeting protocol-specified discontinuation criteria if deriving clinical benefit. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.

Study Overview

Study Type

Interventional

Enrollment (Actual)

1251

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris OBrien Lifehouse ( Site 0300)
      • Port Macquarie, New South Wales, Australia, 2444
        • Port Macquarie Base Hospital ( Site 0301)
      • Wagga Wagga, New South Wales, Australia, 2650
        • Riverina Cancer Care Center ( Site 0302)
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
        • Gallipoli Medical Research Foundation ( Site 0309)
      • Tugun, Queensland, Australia, 4224
        • John Flynn Hospital & Medical Centre ( Site 0308)
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital ( Site 0304)
      • Clayton, Victoria, Australia, 3168
        • Monash Health ( Site 0305)
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre ( Site 0306)
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Fiona Stanley Hospital ( Site 0311)
      • Salzburg, Austria, 5020
        • Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900)
      • Wien, Austria, 1020
        • Krankenhaus der Barmherzigen Brüder Wien ( Site 0904)
      • Wien, Austria, 1090
        • Medizinische Universitaet Wien ( Site 0903)
    • Oberosterreich
      • Linz, Oberosterreich, Austria, 4020
        • Ordensklinikum Linz GmbH Elisabethinen ( Site 0901)
      • Sao Paulo, Brazil, 01246-000
        • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305)
    • Ceara
      • Fortaleza, Ceara, Brazil, 60135-237
        • Oncocentro Ceara ( Site 2309)
    • Parana
      • Curitiba, Parana, Brazil, 80510-130
        • Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306)
    • Rio Grande Do Sul
      • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
        • Hospital Sao Vicente de Paulo ( Site 2303)
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre ( Site 2304)
    • Santa Catarina
      • Blumenau, Santa Catarina, Brazil, 89010-340
        • Clinica de Oncologia Reichow ( Site 2308)
    • Sao Paulo
      • Jau, Sao Paulo, Brazil, 17210-120
        • Fundacao Dr Amaral Carvalho ( Site 2302)
      • Quebec, Canada, G1R 2J6
        • CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0101)
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital ( Site 0100)
      • St. Catharines, Ontario, Canada, L2S 0A9
        • Niagara Health System - St. Catharines ( Site 0107)
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • CISSS de la Monteregie-Centre ( Site 0105)
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109)
      • Montreal, Quebec, Canada, H3T 1M5
        • CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106)
    • Araucania
      • Temuco, Araucania, Chile, 4780000
        • Centro Investigación del Cáncer James Lind ( Site 2401)
    • Coquimbo
      • La Serena, Coquimbo, Chile, 1720430
        • IC La Serena Research ( Site 2406)
    • Maule
      • Talca, Maule, Chile, 3465584
        • Clinica Universidad Catolica del Maule ( Site 2407)
    • Region M. De Santiago
      • Santiago, Region M. De Santiago, Chile, 7650568
        • Clinica Alemana ( Site 2408)
      • Santiago, Region M. De Santiago, Chile, 8330032
        • Pontificia Universidad Catolica de Chile ( Site 2402)
      • Santiago, Region M. De Santiago, Chile, 8420383
        • Sociedad Medica Aren y Bachero Limitada ( Site 2403)
    • Valparaiso
      • Vina del Mar, Valparaiso, Chile, 2520598
        • Oncocentro ( Site 2400)
    • Beijing
      • Beijing, Beijing, China, 100034
        • Peking University First Hospital ( Site 0800)
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310014
        • Zhejiang Provincial People's Hospital ( Site 0809)
      • Wenzhou, Zhejiang, China, 325000
        • The First Affiliated Hospital of Wenzhou Medical University ( Site 0834)
    • Atlantico
      • Barranquilla, Atlantico, Colombia, 080020
        • Institucion Prestadora de Servicios de Salud Clinica de la Costa LTDA ( Site 2504)
    • Cesar
      • Valledupar, Cesar, Colombia, 200001
        • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509)
    • Distrito Capital De Bogota
      • Bogota, Distrito Capital De Bogota, Colombia, 110221
        • Administradora Country SA - Clinica del Country ( Site 2507)
      • Bogota, Distrito Capital De Bogota, Colombia, 110321
        • Instituto Nacional de Cancerologia E.S.E ( Site 2506)
    • Valle Del Cauca
      • Cali, Valle Del Cauca, Colombia, 760042
        • Hemato Oncologos ( Site 2503)
    • Hovedstaden
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Rigshospitalet ( Site 1005)
      • Herlev, Hovedstaden, Denmark, 2730
        • Herlev og Gentofte Hospital. ( Site 1004)
    • Nordjylland
      • Aalborg, Nordjylland, Denmark, 9000
        • Aalborg Universitetshospital ( Site 1000)
    • Syddanmark
      • Odense, Syddanmark, Denmark, 5000
        • Odense Universitetshospital ( Site 1003)
      • Vejle, Syddanmark, Denmark, 7100
        • Vejle Sygehus ( Site 1002)
    • Mellersta Finland
      • Jyvaskyla, Mellersta Finland, Finland, 40620
        • Keski-Suomen keskussairaala ( Site 1017)
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampereen yliopistollinen sairaala ( Site 1022)
    • Varsinais-Suomi
      • Helsinki, Varsinais-Suomi, Finland, 00290
        • HYKS ( Site 1020)
      • Turku, Varsinais-Suomi, Finland, 20521
        • TYKS T-sairaala Syopatautien pkl ( Site 1019)
    • Auvergne
      • Lyon, Auvergne, France, 69373
        • Centre Leon-Berard ( Site 1110)
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, France, 67200
        • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114)
    • Bretagne
      • Brest, Bretagne, France, 29200
        • CHU de Brest -Site Hopital Morvan ( Site 1103)
    • Cote-d Or
      • Dijon, Cote-d Or, France, 21079
        • Centre Georges Francois Leclerc ( Site 1112)
    • Doubs
      • Besancon, Doubs, France, 25000
        • CHU-Jean Minjoz ( Site 1101)
    • Gironde
      • Bordeaux, Gironde, France, 33076
        • Institut Bergonie ( Site 1104)
    • Hauts-de-Seine
      • Suresnes, Hauts-de-Seine, France, 92151
        • Hopital Foch ( Site 1105)
    • Ille-et-Vilaine
      • Rennes, Ille-et-Vilaine, France, 35033
        • C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117)
    • Marne
      • Reims, Marne, France, 51726
        • Institut Jean Godinot-Clinical Research Unit ( Site 1118)
    • Meurthe-et-Moselle
      • Nancy, Meurthe-et-Moselle, France, 54100
        • Centre D Oncologie de Gentilly ( Site 1107)
    • Nord-Pas-de-Calais
      • Lille, Nord-Pas-de-Calais, France, 59000
        • Centre Bourgogne ( Site 1119)
    • Rhone
      • Pierre Benite, Rhone, France, 69310
        • Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102)
    • Val-de-Marne
      • Creteil, Val-de-Marne, France, 94010
        • Hopital Henri Mondor ( Site 1116)
      • Berlin, Germany, 10117
        • Charite Universitaetsmedizin Berlin ( Site 1201)
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf ( Site 1212)
    • Baden-Wurttemberg
      • Freiburg, Baden-Wurttemberg, Germany, 79106
        • Universitaetsklinikum Freiburg ( Site 1200)
    • Bayern
      • Muenchen, Bayern, Germany, 81377
        • Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210)
      • Munchen, Bayern, Germany, 81675
        • Klinikum Rechts der Isar ( Site 1206)
      • Nurnberg, Bayern, Germany, 90419
        • Klinikum Nuernberg Nord ( Site 1213)
    • Niedersachsen
      • Braunschweig, Niedersachsen, Germany, 38126
        • Staedtisches Klinikum Braunschweig gGmbH ( Site 1217)
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204)
    • Sachsen-Anhalt
      • Magdeburg, Sachsen-Anhalt, Germany, 39120
        • Universitaetsklinikum Magdeburg A.o.R. ( Site 1211)
      • Cork, Ireland, T12 DC4A
        • Cork University Hospital ( Site 1304)
      • Dublin, Ireland, 00009
        • Beaumont Hospital ( Site 1302)
      • Dublin, Ireland, D24 NR0A
        • Tallaght University Hospital ( Site 1301)
      • Dublin, Ireland, DO4 YN63
        • St Vincents University Hospital ( Site 1300)
      • Limerick, Ireland, V94 F858
        • University Hospital Limerick ( Site 1305)
      • Waterford, Ireland, X91 ER8E
        • University Hospital Waterford ( Site 1303)
      • Haifa, Israel, 3109601
        • Rambam Medical Center ( Site 1400)
      • Jerusalem, Israel, 9112001
        • Hadassah Ein Kerem Medical Center ( Site 1404)
      • Kfar Saba, Israel, 4428164
        • Meir Medical Center ( Site 1401)
      • Petach Tikva, Israel, 4941492
        • Rabin Medical Center ( Site 1402)
      • Tel Aviv, Israel, 6423906
        • Sourasky Medical Center ( Site 1403)
      • Zerifin, Israel, 70300
        • Assaf Harofeh Medical Center ( Site 1405)
      • Bari, Italy, 70124
        • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509)
      • Catania, Italy, 95126
        • Azienda Ospedaliera Cannizzaro ( Site 1501)
      • Milano, Italy, 20133
        • Istituto Nazionale dei Tumori ( Site 1510)
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508)
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli ( Site 1512)
      • Terni, Italy, 05100
        • Azienda Ospedaliera Santa Maria ( Site 1502)
      • Verona, Italy, 37126
        • A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504)
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503)
    • Lombardia
      • Rozzano, Lombardia, Italy, 20089
        • Istituto Clinico Humanitas Research Hospital ( Site 1500)
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Centro Di Riferimento Oncologico ( Site 1511)
      • Chiba, Japan, 260-8717
        • Chiba Cancer Center ( Site 0733)
      • Fukuoka, Japan, 812-0033
        • Harasanshin Hospital ( Site 0747)
      • Nagano, Japan, 381-8551
        • Nagano Municipal Hospital ( Site 0731)
      • Osaka, Japan, 545-8586
        • Osaka City University Hospital ( Site 0741)
      • Tokyo, Japan, 105-8470
        • Toranomon Hospital ( Site 0740)
      • Tokyo, Japan, 113-8603
        • Nippon Medical School Hospital ( Site 0738)
      • Tokyo, Japan, 162-8666
        • Tokyo Women's Medical University Hospital ( Site 0739)
    • Chiba
      • Sakura, Chiba, Japan, 285-8741
        • Toho University Sakura Medical Center ( Site 0732)
    • Ehime
      • Toon, Ehime, Japan, 791-0295
        • Ehime University Hospital ( Site 0745)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital ( Site 0730)
    • Kanagawa
      • Sagamihara, Kanagawa, Japan, 252-0375
        • Kitasato University Hospital ( Site 0734)
      • Yokohama, Kanagawa, Japan, 232-0024
        • Yokohama City University Medical Center ( Site 0735)
    • Nara
      • Kashihara, Nara, Japan, 634-8522
        • Nara Medical University Hospital ( Site 0744)
    • Osaka
      • Osakasayama, Osaka, Japan, 589-8511
        • Kindai University Hospital ( Site 0743)
      • Suita, Osaka, Japan, 565-0871
        • Osaka University Hospital ( Site 0742)
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Saitama Medical University International Medical Center ( Site 0737)
      • Koshigaya, Saitama, Japan, 343-8555
        • Dokkyo Medical University Saitama Medical Center ( Site 0736)
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan, 431-3192
        • Hamamatsu University Hospital ( Site 0748)
    • Yamaguchi
      • Ube, Yamaguchi, Japan, 755-8505
        • Yamaguchi University Hospital ( Site 0746)
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital ( Site 0405)
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System ( Site 0402)
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center ( Site 0403)
    • Jeonranamdo
      • Jeollanam-do, Jeonranamdo, Korea, Republic of, 58128
        • Chonnam National University Hwasun Hospital ( Site 0406)
    • Kyonggi-do
      • Gyeonggi-do, Kyonggi-do, Korea, Republic of, 10408
        • National Cancer Center ( Site 0400)
      • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital ( Site 0401)
    • Taegu-Kwangyokshi
      • Daegu, Taegu-Kwangyokshi, Korea, Republic of, 41404
        • Kyungpook National University Chilgok Hospital ( Site 0404)
      • Chihuahua, Mexico, 31000
        • Centro Estatal de Cancerologia de Chihuahua ( Site 2608)
      • Mexico City, Mexico, 03310
        • Grupo Medico Camino SC ( Site 2613)
      • Mexico City, Mexico, 04700
        • Centro Oncologico Internacional. SEDNA ( Site 2609)
      • Queretaro, Mexico, 76070
        • Boca Raton Clinical Research QTO ( Site 2611)
    • Chiapas
      • Tuxtla Gutierrez, Chiapas, Mexico, 29090
        • Hospital San Lucas Cardiologica del Sureste ( Site 2606)
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44280
        • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607)
      • Utrecht, Netherlands, 3543 AZ
        • St. Antonius Ziekenhuis ( Site 1600)
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • Radboud University Medical Center ( Site 1606)
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek Ziekenhuis ( Site 1603)
      • Amsterdam, Noord-Holland, Netherlands, 1081 HV
        • Vrije Universiteit Medisch Centrum ( Site 1601)
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8025 AB
        • Isala Klinieken, Locatie Sophia ( Site 1604)
    • Utrecht
      • Amersfoort, Utrecht, Netherlands, 3813 TZ
        • Meander Medisch Centrum ( Site 1602)
    • Zuid-Holland
      • Schiedam, Zuid-Holland, Netherlands, 3118 JH
        • Franciscus Gasthuis en Vlietland ( Site 1605)
      • Auckland, New Zealand, 1023
        • Auckland City Hospital ( Site 0321)
      • Lima, Peru, 15033
        • Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708)
      • Lima, Peru, 15036
        • Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 2706)
      • Lima, Peru, 15076
        • Hospital Militar Central [Lima, Peru] ( Site 2704)
    • Ariqipa
      • Arequipa, Ariqipa, Peru, 04001
        • Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700)
    • La Libertad
      • Trujillo, La Libertad, Peru, 13011
        • Clinica Peruano Americana S.A. ( Site 2702)
    • Kujawsko-pomorskie
      • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
        • Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720)
      • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716)
      • Torun, Kujawsko-pomorskie, Poland, 87-100
        • Nasz Lekarz Przychodnie Medyczne ( Site 1718)
    • Malopolskie
      • Krakow, Malopolskie, Poland, 30-688
        • Szpital Uniwersytecki w Krakowie ( Site 1707)
    • Mazowieckie
      • Radom, Mazowieckie, Poland, 26-600
        • Radomskie Centrum Onkologii ( Site 1701)
    • Podkarpackie
      • Przemysl, Podkarpackie, Poland, 37-700
        • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700)
    • Slaskie
      • Bytom, Slaskie, Poland, 41-902
        • Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717)
    • Wielkopolskie
      • Poznan, Wielkopolskie, Poland, 61-848
        • Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
    • Zachodniopomorskie
      • Koszalin, Zachodniopomorskie, Poland, 75-581
        • Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709)
      • Szczecin, Zachodniopomorskie, Poland, 71-434
        • Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721)
    • Krasnoyarskiy Kray
      • Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133
        • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810)
    • Moskva
      • Moscow, Moskva, Russian Federation, 105077
        • SBIH City clinical hospital named after D.D. Pletniov ( Site 1813)
      • Moscow, Moskva, Russian Federation, 117997
        • Russian Scientific Center of Roentgenoradiology ( Site 1800)
    • Nizhegorodskaya Oblast
      • Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603074
        • Volga District Medical Center Federal Medical and Biological Agency ( Site 1805)
    • Omskaya Oblast
      • Omsk, Omskaya Oblast, Russian Federation, 644013
        • Omsk Clinical Oncology Dispensary ( Site 1809)
      • Lugo, Spain, 27003
        • Hospital Universitario Lucus Augusti ( Site 1905)
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal ( Site 1902)
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos ( Site 1906)
      • Madrid, Spain, 28041
        • Hospital 12 de Octubre de Madrid ( Site 1903)
      • Sevilla, Spain, 41071
        • Hospital Virgen de la Macarena ( Site 1904)
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Instituto Catalan de Oncologia - ICO ( Site 1901)
    • Gerona
      • Girona, Gerona, Spain, 17007
        • Hospital Josep Trueta ( Site 1900)
    • Grisons
      • Chur, Grisons, Switzerland, 7000
        • Kantonsspital Graubuenden ( Site 2003)
    • Sankt Gallen
      • St. Gallen, Sankt Gallen, Switzerland, 9007
        • Kantonsspital St. Gallen ( Site 2000)
    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • CHUV (centre hospitalier universitaire vaudois) ( Site 2002)
    • Zurich
      • Zuerich, Zurich, Switzerland, 8091
        • Universitaetsspital Zuerich ( Site 2001)
      • Kaohsiung, Taiwan, 83301
        • Kaohsiung Chang Gung Memorial Hospital ( Site 0504)
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital ( Site 0503)
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital ( Site 0500)
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital ( Site 0501)
      • Taoyuan, Taiwan, 333
        • Chang Gung Medical Foundation. Linkou ( Site 0502)
      • Khon Kaen, Thailand, 40002
        • Srinagarind Hospital ( Site 0604)
    • Krung Thep Maha Nakhon
      • Bangkok, Krung Thep Maha Nakhon, Thailand, 10330
        • Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600)
      • Bangkok, Krung Thep Maha Nakhon, Thailand, 10400
        • Ramathibodi Hospital. ( Site 0601)
      • Bangkok, Krung Thep Maha Nakhon, Thailand, 10700
        • Faculty of Medicine Siriraj Hospital ( Site 0602)
      • Adana, Turkey, 01130
        • Acibadem Adana Hastanesi ( Site 2106)
      • Ankara, Turkey, 06100
        • Ankara Universitesi Tip Fakultesi. ( Site 2101)
      • Ankara, Turkey, 06230
        • Hacettepe Universitesi Tıp Fakultesi ( Site 2105)
      • Ankara, Turkey, 06800
        • Ankara Sehir Hastanesi ( Site 2103)
      • Istanbul, Turkey, 34098
        • Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100)
      • Izmir, Turkey, 35100
        • Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102)
      • Konya, Turkey, 42080
        • Konya Necmettin Erbakan University Medical Faculty ( Site 2104)
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre Hospital ( Site 1322)
    • Aberdeen City
      • Aberdeen, Aberdeen City, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary ( Site 1315)
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospitals NHS Trust ( Site 1317)
    • London, City Of
      • London, London, City Of, United Kingdom, NW1 2BU
        • University College London Hospitals NHS Foundation Trust ( Site 1320)
      • London, London, City Of, United Kingdom, SW3 6JJ
        • Royal Marsden NHS Foundation Trust ( Site 1318)
    • Alaska
      • Anchorage, Alaska, United States, 99503
        • Alaska Clinical Research Center ( Site 0274)
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center ( Site 0276)
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center ( Site 0217)
      • Los Angeles, California, United States, 90404
        • UCLA Hematology/Oncology - Santa Monica ( Site 0241)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado, Anschutz Cancer Pavilion ( Site 0236)
    • Connecticut
      • Manchester, Connecticut, United States, 06042
        • Hartford HealthCare Medical Group ( Site 0212)
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Center at Yale-New Haven ( Site 0250)
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • Sibley Memorial Hospital ( Site 0275)
    • Georgia
      • Atlanta, Georgia, United States, 30322-1013
        • Winship Cancer Institute of Emory University ( Site 0209)
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago ( Site 0264)
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic [Springfield, IL] ( Site 0240)
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton-O'Neil Cancer Center ( Site 0228)
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Sidney Kimmel Comprehensive Cancer Center ( Site 0204)
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center-Research ( Site 0213)
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada ( Site 0269)
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270)
      • New York, New York, United States, 10065
        • Weill Cornell Medical College ( Site 0263)
      • Syracuse, New York, United States, 13210
        • Associated Medical Professionals of NY ( Site 0251)
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University ( Site 0206)
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • Tri-State Urologic Services PSC, Inc. ( Site 0253)
    • Pennsylvania
      • Bala-Cynwyd, Pennsylvania, United States, 19004
        • MidLantic Urology ( Site 0273)
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • Ralph H. Johnson VA Center ( Site 0256)
      • Myrtle Beach, South Carolina, United States, 29572
        • Carolina Urologic Research Center ( Site 0259)
    • Tennessee
      • Nashville, Tennessee, United States, 37209
        • Urology Associates [Nashville, TN] ( Site 0233)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Health System ( Site 0205)
      • Virginia Beach, Virginia, United States, 23462
        • Urology of Virginia ( Site 0224)
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance ( Site 0258)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
  • Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
  • Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
  • Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
  • Has adequate organ function
  • Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
  • Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
  • Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex

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 has current pneumonitis
  • Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has a history of seizure or any condition that may predispose to seizure
  • Has a history of loss of consciousness within 12 months of screening
  • Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
  • Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
  • Has a history of clinically significant ventricular arrhythmias
  • Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
  • Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
  • Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
  • 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-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Has received a live vaccine within 30 days prior to randomization
  • Has a "superscan" bone scan
  • Has had an allogenic tissue/solid organ transplant
  • 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 received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:

    1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
    2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
    3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
    4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.
Other Names:
  • MK-3475
  • KEYTRUDA®
Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.
Other Names:
  • XTANDI®
Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.
Placebo Comparator: Placebo + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.
Other Names:
  • XTANDI®
Placebo infusion solution is administered as an IV infusion on Day 1 of each 21-day cycle for up to 35 cycles.
Stable regimen of ADT (LHRH agonist or antagonist) at a dose and frequency of administration that is consistent with the local product label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to approximately 32 months
rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.
Up to approximately 32 months
Overall Survival (OS)
Time Frame: Up to approximately 32 months
OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Up to approximately 32 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)
Time Frame: Up to Approximately 32 months
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. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.
Up to Approximately 32 months
Time to First Symptomatic Skeletal-related Event (TTSSRE)
Time Frame: Up to Approximately 32 months
TTSSRE 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 nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.
Up to Approximately 32 months
Time to Prostate-specific Antigen (PSA) Progression
Time Frame: Up to Approximately 32 months
Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was 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. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.
Up to Approximately 32 months
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR
Time Frame: Up to Approximately 32 months
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 Approximately 32 months
Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use
Time Frame: Up to Approximately 32 months
TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a >2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) 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 the average worst pain score >4 and no decrease in average opioid use. TTPP was calculated using the 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 Approximately 32 months
Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)
Time Frame: Up to Approximately 32 months
PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.
Up to Approximately 32 months
Prostate-specific Antigen (PSA) Response Rate
Time Frame: Up to Approximately 32 Months
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.
Up to Approximately 32 Months
Prostate-specific Antigen (PSA) Undetectable
Time Frame: Up to Approximately 32 Months
PSA undetectable rate was defined as the percentage of participants with detectable PSA (> 0.2 ng/mL) at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment.
Up to Approximately 32 Months
Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR
Time Frame: Up to Approximately 32 Months
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 base 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 Approximately 32 Months
Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR
Time Frame: Up to Approximately 32 Months
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 a 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.
Up to Approximately 32 Months
Number of Participants Who Experience an Adverse Event (AE)
Time Frame: Up to Approximately 59 Months
An AE was defined as 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 unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.
Up to Approximately 59 Months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to Approximately 59 Months
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 can therefore be any unfavourable 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 discontinue study treatment due to an AE will be reported for each arm.
Up to Approximately 59 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2020

Primary Completion (Actual)

October 31, 2022

Study Completion (Estimated)

February 2, 2026

Study Registration Dates

First Submitted

December 5, 2019

First Submitted That Met QC Criteria

December 5, 2019

First Posted (Actual)

December 9, 2019

Study Record Updates

Last Update Posted (Estimated)

November 17, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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