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)

Bladder Cancer Clinical Trial

— KEYNOTE-B15  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04700124
• Other study ID #: 3475-B15
• Secondary ID: MK-3475-B15KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 21, 2021
• Est. completion date: December 23, 2026

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 784
• Est. completion date: December 23, 2026
• Est. primary completion date: December 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (=50%) urothelial histology.
• Have clinically non-metastatic bladder cancer (N=1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
• Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have adequate organ function.

Exclusion Criteria:

• Has a known additional malignancy that is progressing or has required active anti-cancer treatment =3 years of study randomization with certain exceptions
• Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
• Has =N2 disease or metastatic disease (M1) as identified by imaging
• Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
• Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
• Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
• Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
• Has a known psychiatric or substance abuse disorder
• Has had an allogenic tissue/solid organ transplant
• Has ongoing sensory or motor neuropathy Grade 2 or higher
• Has active keratitis (superficial punctate keratitis) or corneal ulcerations
• Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) =8% or HbA1c 7% to <8% with associated diabetes symptoms

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires ( Site 1554)	ABB	Caba
Argentina	Asociación de Beneficencia Hospital Sirio Libanés ( Site 1553)	Buenos Aires
Argentina	Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 1558)	Buenos Aires	Caba
Argentina	Centro de Urología (CDU) ( Site 1552)	Buenos Aires
Argentina	Hospital Británico de Buenos Aires-Oncology ( Site 1551)	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	Fundacion Estudios Clinicos-Oncology ( Site 1557)	Rosario	Santa Fe
Australia	Lyell McEwin Hospital ( Site 1252)	Elizabeth Vale	South Australia
Australia	Frankston Hospital-Oncology and Haematology ( Site 1258)	Frankston	Victoria
Australia	Macquarie University-MQ Health Clinical Trials Unit ( Site 1259)	Macquarie University	New South Wales
Australia	Mater Hospital Brisbane ( Site 1257)	South Brisbane	Queensland
Bulgaria	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
Canada	Moncton Hospital ( Site 0107)	Moncton	New Brunswick
Canada	Jewish General Hospital ( Site 0106)	Montreal	Quebec
Canada	Ottawa Hospital Research Institute ( Site 0109)	Ottawa	Ontario
Canada	BC Cancer - Vancouver Center ( Site 0110)	Vancouver	British Columbia
Canada	CancerCare Manitoba ( Site 0108)	Winnipeg	Manitoba
China	Hunan Cancer Hospital ( Site 1403)	Changsha	Hunan
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University ( Site 1413)	Guangzhou	Guangdong
China	SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1406)	Guangzhou	Guangdong
China	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S	Nanjing	Jiangsu
China	Nantong Tumor Hospital-Urology ( Site 1405)	Nantong	Jiangsu
China	Fudan University Shanghai Cancer Center-Urology department ( Site 1401)	Shanghai	Shanghai
China	Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1402)	Shanghai	Shanghai
Colombia	Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1654)	Bogota	Distrito Capital De Bogota
Colombia	Fundacion Valle del Lili- CIC ( Site 1656)	Cali	Valle Del Cauca
Colombia	Fundación Colombiana de Cancerología Clínica Vida ( Site 1653)	Medellin	Antioquia
Colombia	Oncomédica S.A.S ( Site 1652)	Montería	Cordoba
Colombia	Fundación Cardiovascular de Colombia-Santander ( Site 1657)	Piedecuesta	Santander
Croatia	Klinicki bolnicki centar Osijek ( Site 1705)	Osijek	Osjecko-baranjska Zupanija
Croatia	Klinicki Bolnicki Centar Split-Oncology and Radiotherapy ( Site 1702)	Split	Splitsko-dalmatinska Zupanija
Croatia	Klinicki bolnicki centar Sestre milosrdnice ( Site 1703)	Zagreb	Grad Zagreb
Croatia	Klinicki bolnicki centar Zagreb-Klinika za onkologiju ( Site 1701)	Zagreb	Grad Zagreb
Czechia	Fakultni nemocnice u sv. Anny v Brne ( Site 0253)	Brno	Jihomoravsky Kraj
Czechia	Fakultni nemocnice Hradec Kralove-Klinika onkologie a radioterapie ( Site 0254)	Hradec Kralove
Czechia	Fakultni Nemocnice Olomouc ( Site 0251)	Olomouc
Czechia	Fakultni Thomayerova nemocnice ( Site 0252)	Praha 4
France	CHU Jean Minjoz ( Site 0453)	Besancon	Doubs
France	CHU de Brest -Site Hopital Morvan ( Site 0461)	Brest	Finistere
France	CHU GRENOBLE ALPES ( Site 0468)	La Tronche	Isere
France	Polyclinique du Bois ( Site 0458)	Lille	Nord
France	CHU Limoges Hopital Dupuytren ( Site 0459)	Limoges	Haute-Vienne
France	CHU La Timone ( Site 0456)	Marseille	Bouches-du-Rhone
France	Centre Hospitalier Regional du Orleans ( Site 0463)	Orleans	Loiret
France	Hopital Diaconesses Croix Saint Simon ( Site 0465)	Paris
France	Institut Universitaire du Cancer Toulouse - Oncopole ( Site 0455)	Toulouse	Haute-Garonne
France	Gustave Roussy ( Site 0467)	Villejuif	Ile-de-France
Germany	Vivantes Klinikum Am Urban ( Site 0519)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 0509)	Dresden	Sachsen
Germany	Universitaetsklinikum Freiburg ( Site 0512)	Freiburg	Baden-Wurttemberg
Germany	Krankenhaus Martha Maria Halle-Doelau ( Site 0507)	Halle	Sachsen-Anhalt
Germany	Kath. Krankenhaus Marienhospital. Universitaetsklinik ( Site 0511)	Herne	Nordrhein-Westfalen
Germany	Universitaetsklinikum Muenster ( Site 0516)	Muenster	Nordrhein-Westfalen
Germany	Caritas Krankenhaus St. Josef ( Site 0502)	Regensburg	Bayern
Germany	Universitaetsklinik fuer Urologie ( Site 0501)	Tuebingen	Baden-Wurttemberg
Germany	Universitaetsklinikum Wuerzburg ( Site 0520)	Wuerzburg	Bayern
Greece	Athens Medical Center ( Site 0304)	Athens	Attiki
Greece	General Hospital of Athens "Alexandra" ( Site 0303)	Athens	Attiki
Greece	ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0301)	Chaidari	Attiki
Greece	University General Hospital of Larissa ( Site 0302)	Larissa	Thessalia
Greece	UNIVERSITY HOSPITAL OF PATRAS-DIVISION OF ONCOLOGY ( Site 0305)	Patras	Achaia
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 1006)	Debrecen
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ ( Site 1010)	Szeged	Csongrad
Hungary	Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1002)	Szolnok	Jasz-Nagykun-Szolnok
Israel	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)	Zerifin
Italy	Azienda Ospedaliero Universitaria delle Marche-Clinica Oncologica ( Site 0593)	Ancona
Italy	Ospedale Cannizzaro ( Site 0590)	Catania
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0588)	Milan	Lombardia
Italy	IRCCS Ospedale San Raffaele ( Site 0596)	Milano
Italy	AOU San Luigi Gonzaga di Orbassano ( Site 0595)	Orbassano	Torino
Italy	Istituto Oncologico Veneto IRCCS-Oncologia Medica 1 ( Site 0600)	Padova
Italy	Presidio Ospedaliero Santa Maria delle Grazie ( Site 0599)	Pozzuoli	Napoli
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento ( Site 0598)	Verona	Veneto
Japan	Gifu University Hospital ( Site 1513)	Gifu
Japan	Hamamatsu University Hospital ( Site 1511)	Hamamatsu	Shizuoka
Japan	Hirosaki University Hospital ( Site 1501)	Hirosaki	Aomori
Japan	Kanazawa University Hospital ( Site 1509)	Kanazawa	Ishikawa
Japan	Nagasaki University Hospital ( Site 1517)	Nagasaki
Japan	Nagoya University Hospital ( Site 1512)	Nagoya	Aichi
Japan	Okayama University Hospital ( Site 1516)	Okayama
Japan	Osaka International Cancer Institute ( Site 1514)	Osaka
Japan	Osaka Metropolitan University Hospital ( Site 1515)	Osaka
Japan	Kitasato University Hospital ( Site 1506)	Sagamihara	Kanagawa
Japan	Tohoku University Hospital ( Site 1503)	Sendai	Miyagi
Japan	Keio University Hospital ( Site 1504)	Tokyo
Japan	Tokyo Medical and Dental University Hospital ( Site 1505)	Tokyo
Japan	Toyama University Hospital ( Site 1510)	Toyama
Japan	University of Tsukuba Hospital ( Site 1502)	Tsukuba	Ibaraki
Japan	Kanagawa Cancer Center ( Site 1507)	Yokohama	Kanagawa
Japan	Yokohama City University Medical Center ( Site 1508)	Yokohama	Kanagawa
Korea, Republic of	Kyungpook National University Chilgok Hospital ( Site 1354)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Seoul National University Bundang Hospital ( Site 1355)	Gyeonggi-do	Kyonggi-do
Korea, Republic of	Gachon University Gil Medical Center ( Site 1356)	Incheon
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 1353)	Jeollanam-do	Jeonranamdo
Korea, Republic of	Korea University Anam Hospital ( Site 1357)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1351)	Seoul
Korea, Republic of	Asan Medical Center ( Site 1352)	Songpagu	Seoul
Malaysia	Hospital Pulau Pinang ( Site 0355)	George Town	Pulau Pinang
Malaysia	Sarawak General Hospital ( Site 0351)	Kuching	Sarawak
Malaysia	University Malaya Medical Centre ( Site 0352)	Lembah Pantai	Kuala Lumpur
Malaysia	Sunway Medical Centre ( Site 0353)	Petaling Jaya	Selangor
Philippines	THE MEDICAL CITY ILOILO-The Medical City Iloilo - Clinical and Translational Research Institute-Ilo	Iloilo City	Iloilo
Poland	Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1055)	Koszalin	Zachodniopomorskie
Poland	Clinical Research Center Medic-R ( Site 1061)	Poznan	Wielkopolskie
Poland	Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1053)	Przemysl	Podkarpackie
Poland	Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1057)	Siedlce	Mazowieckie
Poland	Narodowy Instytut Onkologii ( Site 1051)	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu ( Site 1058)	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar e Universitario de Coimbra ( Site 0406)	Coimbra
Portugal	CHLO, EPE - Hospital de Sao Francisco Xavier ( Site 0401)	Lisboa
Portugal	Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0409)	Lisboa
Portugal	Hospital Geral de Santo Antonio ( Site 0408)	Porto
Romania	SC Focus Lab Plus SRL ( Site 1104)	Bucuresti
Romania	Institutul Oncologic Cluj-Oncologie Medicala ( Site 1109)	Cluj
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 1102)	Cluj Napoca	Cluj
Romania	Cardiomed SRL Cluj-Napoca ( Site 1101)	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)	Timisoara	Timis
Russian Federation	Altay Regional Oncology Dispensary ( Site 0851)	Barnaul	Altayskiy Kray
Russian Federation	Sverdlovsk Regional Oncology Hospital ( Site 0867)	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	Sverdlovsky Regional Clinical hospital #1 ( Site 0868)	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	First Moscow State Medical University n.a. I.M.Sechenov ( Site 0871)	Moscow	Moskva
Russian Federation	National Medical Research Centre of Oncology named after N.N. Blokhin ( Site 0865)	Moscow	Moskva
Russian Federation	Volga District Medical Center ( Site 0876)	Nizhny Novgorod	Nizhegorodskaya Oblast
Russian Federation	National Medical Research Radiology Centre ( Site 0869)	Obninsk	Kaluzskaja Oblast
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0852)	Saint Petersburg	Sankt-Peterburg
Russian Federation	St.Petersburg Clinical Hospital RAS ( Site 0864)	Saint Petersburg	Sankt-Peterburg
Russian Federation	St.Petersburg State Medical Univ. n.a. acad. I.P.Pavlov ( Site 0856)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Volgograd Regional Uronephrological Center ( Site 0870)	Volzhsky	Volgogradskaya Oblast
Singapore	Tan Tock Seng Hospital ( Site 0704)	Singapore	Central Singapore
South Africa	Groote Schuur Hospital ( Site 0602)	Cape Town	Western Cape
South Africa	Wits Clinical Research ( Site 0603)	Johannesburg	Gauteng
South Africa	Steve Biko Academic Hospital ( Site 0601)	Pretoria	Gauteng
Spain	Hospital Germans Trias i Pujol. ICO de Badalona ( Site 0658)	Badalona	Barcelona
Spain	Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0661)	Barcelona
Spain	Institut Català d'Oncologia (ICO) - Girona ( Site 0653)	Girona	Gerona
Spain	Hospital Universitario Insular de Gran Canaria ( Site 0657)	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital Clinico Universitario San Carlos de Madrid ( Site 0651)	Madrid
Spain	Xarxa Assistencial Universitaria Manresa ( Site 0655)	Manresa	Barcelona
Spain	Hospital Universitario Central de Asturias ( Site 0654)	Oviedo	Asturias
Spain	CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 0660)	Santiago de Compostela	La Coruna
Spain	Hospital Virgen del Rocio ( Site 0659)	Sevilla
Spain	Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0662)	Valencia	Valenciana, Comunitat
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 1203)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	China Medical University Hospital ( Site 1202)	Taichung
Taiwan	Taipei Veterans General Hospital ( Site 1201)	Taipei
Ukraine	I.I. Mechnykov Dnipropetrovsk Regional Clinical Hospital ( Site 0959)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Clinical oncology dispensary of Dnipropetrovsk regional council ( Site 0954)	Dnipro	Dnipropetrovska Oblast
Ukraine	MNPE Regional Center of Oncology ( Site 0955)	Kharkiv	Kharkivska Oblast
Ukraine	Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0965)	Kharkiv	Kharkivska Oblast
Ukraine	Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval ( Site 0952)	Kharkiv	Kharkivska Oblast
Ukraine	Lviv Oncology Regional Treatment and Diagnostic Center ( Site 0960)	Lviv	Lvivska Oblast
Ukraine	Zhytomyr Regional Oncology Center ( Site 0961)	Zhytomyr	Zhytomyrska Oblast
United Kingdom	Imperial College Healthcare NHS Foundation Trust - St Mary's Hospital ( Site 1802)	London	London, City Of
United Kingdom	St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 1801)	London	London, City Of
United Kingdom	Torbay Hospital ( Site 1804)	Torquay	Devon
United States	University of Colorado, Anschutz Cancer Pavilion ( Site 0009)	Aurora	Colorado
United States	MidLantic Urology ( Site 0002)	Bala-Cynwyd	Pennsylvania
United States	UT Southwestern Medical Center ( Site 0003)	Dallas	Texas
United States	Duke University Medical Center ( Site 0017)	Durham	North Carolina
United States	St Joseph Heritage Healthcare-Oncology ( Site 0035)	Fullerton	California
United States	UF Health ( Site 0031)	Gainesville	Florida
United States	Saint Francis Cancer Center ( Site 0008)	Greenville	South Carolina
United States	Houston Methodist Urology Associates ( Site 0033)	Houston	Texas
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	The University of Tennessee Medical Center ( Site 0034)	Knoxville	Tennessee
United States	UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro	Los Angeles	California
United States	University of Louisville, James Graham Brown Cancer Center ( Site 0022)	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics ( Site 0037)	Madison	Wisconsin
United States	Icahn School of Medicine at Mount Sinai ( Site 0011)	New York	New York
United States	Mayo Clinic in Arizona - Phoenix ( Site 0043)	Phoenix	Arizona
United States	Oregon Health and Science University ( Site 0028)	Portland	Oregon
United States	Urology of San Antonio ( Site 0020)	San Antonio	Texas
United States	University of California San Francisco ( Site 0010)	San Francisco	California
United States	Stanford University ( Site 0023)	Stanford	California
United States	White Plains Hospital ( Site 0039)	White Plains	New York
United States	Wake Forest Baptist Health ( Site 0014)	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Astellas Pharma Inc, Seagen Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  China,  Colombia,  Croatia,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival (EFS)	EFS is defined as the time from randomization to the first occurrence of following events: radiographic disease progression precluding RC + PLND, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause.	Up to ~68 months
Secondary	Pathologic Complete Response (pCR) Rate	pCR rate is defined as defined as the proportion of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from radical cystectomy (RC) + pelvic lymph node dissection (PLND), as assessed by blinded central pathologic review.	Up to ~47 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~68 months
Secondary	Disease Free Survival (DFS)	DFS is defined as the time from postsurgery baseline scan until the first occurrence of either local/distant recurrence as assessed by BICR imaging and/or biopsy or death from any cause.	From ~12 months to up to ~68 months
Secondary	Pathologic Downstaging (pDS) Rate	pDS is defined as participants with	Up to ~47 months
Secondary	Number of Participants Who Experienced An Adverse Event (AE) (Arm A only)	An AE is 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. The number of participants who experience an AE will be presented.	Up to ~68 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to An AE (Arm A only)	An AE is 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. The number of participants who discontinue study treatment due to an AE will be presented.	Up to ~68 months
Secondary	Number of Participants Experiencing Perioperative Complications	Perioperative complications are defined as both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy. The number of participants experiencing perioperative complications will be presented.	Up to ~68 months
Secondary	Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Participant responses to questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). A higher score indicates a better overall health/quality of life status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented.	Baseline, Up to ~68 months
Secondary	Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.	Baseline, Up to ~68 months
Secondary	Change From Baseline in Urinary, Bowel and Sexual Domains per Bladder Cancer Index (BCI)	The BCI is a 36-item validated, condition-specific health questionnaire to assess the quality of life among participants with bladder cancer. The BCI contains 3 domains: urinary (14 items), bowel (10 items), and sexual (12 items) with function (Likert response scale: 0 [Never] - 4 [Always]) and bother (Likert response scale: 0 [No problem] - 4 [Big problem]) subdomains. The domain and subdomain scores are standardized to a 0 to 100 point scale where higher scores correspond better functioning and health-related qualify of life. The change from baseline in the combined scores of the urinary, bowel, and sexual domains of the BCI will be presented.	Baseline, Up to ~68 months
Secondary	Change from Baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS)	The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.	Baseline, Up to ~68 months
Secondary	Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score (Items 6-7)	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a better level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.	Baseline, Up to ~68 months

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