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COMPLETED
NCT04700124
PHASE3

Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304)

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).

Official title: A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

808

Start Date

2021-04-21

Completion Date

2025-10-27

Last Updated

2026-06-26

Healthy Volunteers

No

Conditions

Interventions

BIOLOGICAL

Pembrolizumab

200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.

BIOLOGICAL

Enfortumab vedotin (EV)

1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length = 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length = 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.

PROCEDURE

RC + PLND

Curative intent RC + PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC + PLND to be done approximately at 15 weeks from randomization).

DRUG

Gemcitabine

1000 mg/m\^2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

DRUG

Cisplatin

70 mg/m\^2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)

Locations (188)

Mayo Clinic in Arizona - Phoenix ( Site 0043)

Phoenix, Arizona, United States

St Joseph Heritage Healthcare-Oncology ( Site 0035)

Fullerton, California, United States

UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 0005)

Los Angeles, California, United States

University of California San Francisco ( Site 0010)

San Francisco, California, United States

Stanford University ( Site 0023)

Stanford, California, United States

University of Colorado, Anschutz Cancer Pavilion ( Site 0009)

Aurora, Colorado, United States

UF Health ( Site 0031)

Gainesville, Florida, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 0050)

Indianapolis, Indiana, United States

University of Iowa Hospital and Clinics ( Site 0029)

Iowa City, Iowa, United States

University of Louisville, James Graham Brown Cancer Center ( Site 0022)

Louisville, Kentucky, United States

Icahn School of Medicine at Mount Sinai ( Site 0011)

New York, New York, United States

White Plains Hospital ( Site 0039)

White Plains, New York, United States

Duke University Medical Center ( Site 0017)

Durham, North Carolina, United States

Wake Forest Baptist Health ( Site 0014)

Winston-Salem, North Carolina, United States

Oregon Health and Science University ( Site 0028)

Portland, Oregon, United States

MidLantic Urology ( Site 0002)

Bala-Cynwyd, Pennsylvania, United States

Saint Francis Cancer Center ( Site 0008)

Greenville, South Carolina, United States

The University of Tennessee Medical Center ( Site 0034)

Knoxville, Tennessee, United States

UT Southwestern Medical Center ( Site 0003)

Dallas, Texas, United States

Houston Methodist Urology Associates ( Site 0033)

Houston, Texas, United States

Urology of San Antonio ( Site 0020)

San Antonio, Texas, United States

University of Wisconsin Hospital and Clinics ( Site 0037)

Madison, Wisconsin, United States

Hospital Británico de Buenos Aires-Oncology ( Site 1551)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Hospital Italiano de Buenos Aires ( Site 1554)

ABB, Buenos Aires F.D., Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 1553)

Buenos Aires, Buenos Aires F.D., Argentina

Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 1558)

Buenos Aires, Buenos Aires F.D., Argentina

Fundacion Estudios Clinicos-Oncology ( Site 1557)

Rosario, Santa Fe Province, Argentina

Centro de Urología (CDU) ( Site 1552)

Buenos Aires, Argentina

Macquarie University-MQ Health Clinical Trials Unit ( Site 1259)

Macquarie University, New South Wales, Australia

Mater Hospital Brisbane ( Site 1257)

South Brisbane, Queensland, Australia

Lyell McEwin Hospital ( Site 1252)

Elizabeth Vale, South Australia, Australia

Frankston Hospital-Oncology and Haematology ( Site 1258)

Frankston, Victoria, Australia

MHAT "Uni Hospital" OOD ( Site 1154)

Panagyurishte, Pazardzhik, Bulgaria

Complex Oncology Center Plovdiv ( Site 1151)

Plovdiv, Bulgaria

MHAT Central Onco Hospital OOD ( Site 1158)

Plovdiv, Bulgaria

MHAT Serdika ( Site 1152)

Sofia, Bulgaria

BC Cancer - Vancouver Center ( Site 0110)

Vancouver, British Columbia, Canada

CancerCare Manitoba ( Site 0108)

Winnipeg, Manitoba, Canada

Moncton Hospital ( Site 0107)

Moncton, New Brunswick, Canada

Ottawa Hospital Research Institute ( Site 0109)

Ottawa, Ontario, Canada

Département clinique de médecine de laboratoire du CHUM ( Site 0106)

Montreal, Quebec, Canada

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1406)

Guangzhou, Guangdong, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University ( Site 1413)

Guangzhou, Guangdong, China

Hunan Cancer Hospital ( Site 1403)

Changsha, Hunan, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( Site 1404)

Nanjing, Jiangsu, China

Nantong Tumor Hospital-Urology ( Site 1405)

Nantong, Jiangsu, China

Fudan University Shanghai Cancer Center-Urology department ( Site 1401)

Shanghai, Shanghai Municipality, China

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1402)

Shanghai, Shanghai Municipality, China

Fundacion Colombiana de Cancerología Clinica Vida ( Site 1653)

Medellín, Antioquia, Colombia

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1654)

Bogotá, Bogota D.C., Colombia

IMAT S.A.S ( Site 1652)

Montería, Departamento de Córdoba, Colombia

Fundacion Cardiovascular de Colombia ( Site 1657)

Piedecuesta, Santander Department, Colombia

Fundación Valle del Lili ( Site 1656)

Cali, Valle del Cauca Department, Colombia

Klinički bolnički centar Sestre milosrdnice ( Site 1703)

Zagreb, City of Zagreb, Croatia

Klinički bolnički centar Zagreb-Klinika za onkologiju ( Site 1701)

Zagreb, City of Zagreb, Croatia

Klinički bolnički centar Osijek ( Site 1705)

Osijek, County of Osijek-Baranja, Croatia

Klinički Bolnički Centar Split-Oncology and Radiotherapy ( Site 1702)

Split, Split-Dalmatia County, Croatia

Fakultni nemocnice u sv. Anny v Brne ( Site 0253)

Brno, South Moravian, Czechia

Fakultni nemocnice Hradec Kralove-Klinika onkologie a radioterapie ( Site 0254)

Hradec Králové, Czechia

Fakultni Nemocnice Olomouc ( Site 0251)

Olomouc, Czechia

Fakultni Thomayerova nemocnice ( Site 0252)

Prague, Czechia

CHU La Timone ( Site 0456)

Marseille, Bouches-du-Rhone, France

CHU Jean Minjoz ( Site 0453)

Besançon, Doubs, France

C.H. regional Unv. de Brest - Hopital La Cavale Blanche - Institut de Cancerologie et d Imagerie ( Site 0461)

Brest, Finistere, France

Institut Universitaire du Cancer Toulouse - Oncopole ( Site 0455)

Toulouse, Haute-Garonne, France

CHU Limoges Hopital Dupuytren ( Site 0459)

Limoges, Haute-Vienne, France

CHU GRENOBLE ALPES ( Site 0468)

La Tronche, Isere, France

Centre Hospitalier Regional du Orleans ( Site 0463)

Orléans, Loiret, France

Polyclinique du Bois ( Site 0458)

Lille, Nord, France

Hopital Diaconesses Croix Saint Simon ( Site 0465)

Paris, France

Gustave Roussy ( Site 0467)

Villejuif, Île-de-France Region, France

Universitaetsklinikum Freiburg ( Site 0512)

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitaetsklinik fuer Urologie ( Site 0501)

Tübingen, Baden-Wurttemberg, Germany

Caritas Krankenhaus St. Josef ( Site 0502)

Regensburg, Bavaria, Germany

Universitaetsklinikum Wuerzburg ( Site 0520)

Würzburg, Bavaria, Germany

Kath. Krankenhaus Marienhospital. Universitaetsklinik ( Site 0511)

Herne, North Rhine-Westphalia, Germany

Universitaetsklinikum Muenster ( Site 0516)

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus ( Site 0509)

Dresden, Saxony, Germany

Krankenhaus Martha Maria Halle-Doelau ( Site 0507)

Halle, Saxony-Anhalt, Germany

Vivantes Klinikum Am Urban ( Site 0519)

Berlin, Germany

UNIVERSITY HOSPITAL OF PATRAS-DIVISION OF ONCOLOGY ( Site 0305)

Pátrai, Achaia, Greece

General Hospital of Athens "Alexandra" ( Site 0303)

Athens, Attica, Greece

Athens Medical Center ( Site 0304)

Athens, Attica, Greece

ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0301)

Chaïdári, Attica, Greece

University General Hospital of Larissa ( Site 0302)

Larissa, Thessaly, Greece

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ ( Site 1010)

Szeged, Csongrád megye, Hungary

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1002)

Szolnok, Jász-Nagykun-Szolnok, Hungary

Debreceni Egyetem Klinikai Kozpont ( Site 1006)

Debrecen, Hungary

Rambam Health Care Campus-Oncology ( Site 0751)

Haifa, Israel

Hadassah Medical Center-Oncology ( Site 0757)

Jerusalem, Israel

Meir Medical Center-oncology ( Site 0754)

Kfar Saba, Israel

Rabin Medical Center-Oncology ( Site 0752)

Petah Tikva, Israel

Sheba Medical Center-ONCOLOGY ( Site 0753)

Ramat Gan, Israel

Sourasky Medical Center-Oncology ( Site 0755)

Tel Aviv, Israel

Yitzhak Shamir Medical Center-Oncology ( Site 0756)

Ẕerifin, Israel

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0588)

Milan, Lombardy, Italy

Presidio Ospedaliero Santa Maria delle Grazie ( Site 0599)

Pozzuoli, Napoli, Italy

AOU San Luigi Gonzaga di Orbassano ( Site 0595)

Orbassano, Torino, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento ( Site 0598)

Verona, Veneto, Italy

Azienda Ospedaliero Universitaria delle Marche-Clinica Oncologica ( Site 0593)

Ancona, Italy

Ospedale Cannizzaro ( Site 0590)

Catania, Italy

IRCCS Ospedale San Raffaele ( Site 0596)

Milan, Italy

Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 0600)

Padova, Italy

Nagoya University Hospital ( Site 1512)

Nagoya, Aichi-ken, Japan

Hirosaki University Hospital ( Site 1501)

Hirosaki, Aomori, Japan

University of Tsukuba Hospital ( Site 1502)

Tsukuba, Ibaraki, Japan

Kanazawa University Hospital ( Site 1509)

Kanazawa, Ishikawa-ken, Japan

Kitasato University Hospital ( Site 1506)

Sagamihara, Kanagawa, Japan

Yokohama City University Medical Center ( Site 1508)

Yokohama, Kanagawa, Japan

Kanagawa Cancer Center ( Site 1507)

Yokohama, Kanagawa, Japan

Tohoku University Hospital ( Site 1503)

Sendai, Miyagi, Japan

Hamamatsu University Hospital ( Site 1511)

Hamamatsu, Shizuoka, Japan

Gifu University Hospital ( Site 1513)

Gifu, Japan

Nagasaki University Hospital ( Site 1517)

Nagasaki, Japan

Okayama University Hospital ( Site 1516)

Okayama, Japan

Osaka Prefectural Hospital Organization Osaka International Cancer Institute ( Site 1514)

Osaka, Japan

Osaka Metropolitan University Hospital ( Site 1515)

Osaka, Japan

Institute of Science Tokyo Hospital ( Site 1505)

Tokyo, Japan

Keio University Hospital ( Site 1504)

Tokyo, Japan

Toyama University Hospital ( Site 1510)

Toyama, Japan

University Malaya Medical Centre ( Site 0352)

Lembah Pantai, Kuala Lumpur, Malaysia

Hospital Pulau Pinang ( Site 0355)

George Town, Pulau Pinang, Malaysia

Sarawak General Hospital ( Site 0351)

Kuching, Sarawak, Malaysia

Sunway Medical Centre ( Site 0353)

Petaling Jaya, Selangor, Malaysia

THE MEDICAL CITY ILOILO-The Medical City Iloilo - Clinical and Translational Research Institute-Ilo ( Site 0801)

Iloilo City, Iloilo, Philippines

Clinical Research Center Medic-R ( Site 1061)

Poznan, Greater Poland Voivodeship, Poland

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1057)

Siedlce, Masovian Voivodeship, Poland

Narodowy Instytut Onkologii ( Site 1051)

Warsaw, Masovian Voivodeship, Poland

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1053)

Przemyśl, Podkarpackie Voivodeship, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu ( Site 1058)

Wrocław, Silesian Voivodeship, Poland

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1055)

Koszalin, West Pomeranian Voivodeship, Poland

Unidade Local de Saude de Coimbra - Hospitais da Universidade de Coimbra ( Site 0406)

Coimbra, Portugal

Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0409)

Lisbon, Portugal

Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 0401)

Lisbon, Portugal

Unidade Local de Saude de Santo António - Hospital Santo António ( Site 0408)

Porto, Portugal

MEMORIAL HEALTHCARE INTERNATIONAL S.R.L. ( Site 1104)

Bucharest, Bucharest, Romania

Cardiomed SRL Cluj-Napoca ( Site 1101)

Cluj-Napoca, Cluj, Romania

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1102)

Cluj-Napoca, Cluj, Romania

Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1103)

Cluj-Napoca, Cluj, Romania

SC Radiotherapy Center Cluj SRL ( Site 1108)

Comuna Floresti, Cluj, Romania

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 1107)

Craiova, Dolj, Romania

Policlinica Oncomed SRL ( Site 1106)

Timișoara, Timiș County, Romania

Institutul Oncologic Cluj-Oncologie Medicala ( Site 1109)

Cluj-Napoca, Romania

Altay Regional Oncology Dispensary ( Site 0851)

Barnaul, Altayskiy Kray, Russia

National Medical Research Radiology Centre ( Site 0869)

Obninsk, Kaluzskaja Oblast, Russia

National Medical Research Centre of Oncology named after N.N. Blokhin ( Site 0865)

Moscow, Moscow, Russia

First Moscow State Medical University n.a. I.M.Sechenov ( Site 0871)

Moscow, Moscow, Russia

Volga District Medical Center ( Site 0876)

Nizhny Novgorod, Nizhny Novgorod Oblast, Russia

St.Petersburg Clinical Hospital RAS ( Site 0864)

Saint Petersburg, Sankt-Peterburg, Russia

St.Petersburg State Medical Univ. n.a. acad. I.P.Pavlov ( Site 0856)

Saint Petersburg, Sankt-Peterburg, Russia

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0852)

Saint Petersburg, Sankt-Peterburg, Russia

Sverdlovsk Regional Oncology Hospital ( Site 0867)

Yekaterinburg, Sverdlovsk Oblast, Russia

Sverdlovsky Regional Clinical hospital #1 ( Site 0868)

Yekaterinburg, Sverdlovsk Oblast, Russia

Volgograd Regional Uronephrological Center ( Site 0870)

Volzhsky, Volgograd Oblast, Russia

Tan Tock Seng Hospital ( Site 0704)

Singapore, Central Singapore, Singapore

Wits Clinical Research ( Site 0603)

Johannesburg, Gauteng, South Africa

Steve Biko Academic Hospital ( Site 0601)

Pretoria, Gauteng, South Africa

Groote Schuur Hospital ( Site 0602)

Cape Town, Western Cape, South Africa

Chonnam National University Hwasun Hospital ( Site 1353)

Jeollanam-do, Jeonranamdo, South Korea

Seoul National University Bundang Hospital ( Site 1355)

Gyeonggi-do, Kyonggi-do, South Korea

Asan Medical Center ( Site 1352)

Songpagu, Seoul, South Korea

Kyungpook National University Chilgok Hospital ( Site 1354)

Daegu, Taegu-Kwangyokshi, South Korea

Gachon University Gil Medical Center ( Site 1356)

Incheon, South Korea

Korea University Anam Hospital ( Site 1357)

Seoul, South Korea

Seoul National University Hospital ( Site 1351)

Seoul, South Korea

Hospital Germans Trias i Pujol. ICO de Badalona ( Site 0658)

Badalona, Barcelona, Spain

Xarxa Assistencial Universitaria Manresa ( Site 0655)

Manresa, Barcelona, Spain

Institut Català d'Oncologia (ICO) - Girona ( Site 0653)

Girona, Gerona, Spain

CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 0660)

Santiago de Compostela, La Coruna, Spain

Hospital Universitario Insular de Gran Canaria ( Site 0657)

Las Palmas de Gran Canaria, Las Palmas, Spain

Hospital Universitario Central de Asturias ( Site 0654)

Oviedo, Principality of Asturias, Spain

Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0662)

Valencia, Valenciana, Comunitat, Spain

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0661)

Barcelona, Spain

Hospital Clinico Universitario San Carlos de Madrid ( Site 0651)

Madrid, Spain

Hospital Virgen del Rocio ( Site 0659)

Seville, Spain

Chang Gung Memorial Hospital at Kaohsiung ( Site 1203)

Kaohsiung City, Taiwan

China Medical University Hospital ( Site 1202)

Taichung, Taiwan

Taipei Veterans General Hospital ( Site 1201)

Taipei, Taiwan

I.I. Mechnykov Dnipropetrovsk Regional Clinical Hospital ( Site 0959)

Dnipro, Dnipropetrovsk Oblast, Ukraine

MI Clinical oncology dispensary of Dnipropetrovsk regional council ( Site 0954)

Dnipro, Dnipropetrovsk Oblast, Ukraine

Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval ( Site 0952)

Kharkiv, Kharkiv Oblast, Ukraine

MNPE Regional Center of Oncology ( Site 0955)

Kharkiv, Kharkiv Oblast, Ukraine

Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0965)

Kharkiv, Kharkiv Oblast, Ukraine

Lviv Oncology Regional Treatment and Diagnostic Center ( Site 0960)

Lviv, Lviv Oblast, Ukraine

Zhytomyr Regional Oncology Center ( Site 0961)

Zhytomyr, Zhytomyr Oblast, Ukraine

Torbay Hospital ( Site 1804)

Torquay, Devon, United Kingdom

Charing Cross Hospital-Oncology Research ( Site 1802)

London, Hammersmith and Fulham, United Kingdom

St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1801)

London, London, City of, United Kingdom