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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
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
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.
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.
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).
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)
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