Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

NCT03924895 | Active Not Recruiting Phase 3 DMC FDA Drug

• 10 other identifiers: 3475-905MK-3475-905KEYNOTE-905EV-303PHRR210911-003890jRCT20312206862023-504932-162031220686U1111-1290-40572018-003809-26
• Study Type: interventional
• Target: 595
• Locations: 28 countries
• Sites: 242

Brief Summary

This is a study of perioperative pembrolizumab or enfortumab vedotin in combination with pembrolizumab in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that perioperative pembrolizumab plus radical cystectomy (RC) plus pelvic lymph node dissection (PLND) and perioperative enfortumab vedotin in combination with pembrolizumab plus RC+PLND will achieve superior event-free survival (EFS) compared with RC+PLND alone. With Amendment 5, outcome measures for programmed cell death ligand 1 (PD-L1) combined positive score (CPS) were removed. With Amendment 8, the primary outcome measure of pathologic complete response (pCR) rates was changed to a secondary outcome measure.

Conditions

Urinary Bladder Cancer, Muscle-invasive

Keywords

Muscle-Invasive Bladder Cancer (MIBC); Enfortumab vedotin (EV); Pembrolizumab (MK-3475)

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS) between Arm C and Arm B

  EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery or failure to undergo RC surgery in participants with residual disease (biopsy-proven muscle-invasive bladder cancer \[MIBC\] will be considered an event regardless of radiographic findings), gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy, or death due to any cause.

  Up to approximately 6.75 years

Secondary Outcomes (11)

• EFS between Arm A and Arm B

  Up to approximately 6.75 years

• Overall Survival (OS) between Arm C and Arm B

  Up to approximately 7.6 years

• OS between Arm A and Arm B

  Up to approximately 7.6 years

• Pathologic Complete Response (pCR) Rate between Arm C and Arm B

  Up to approximately 5.7 years

• pCR Rate between Arm A and Arm B

  Up to approximately 5.7 years

Study Arms (3)

Arm A: Pembrolizumab + Surgery

EXPERIMENTAL

Participants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.

Drug: Pembrolizumab; Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

Arm B: Surgery alone

ACTIVE COMPARATOR

Participants receive standard of care surgery alone.

Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery

EXPERIMENTAL

Participants receive 3 preoperative cycles of enfortumab vedotin + pembrolizumab, followed by standard of care surgery, followed by 6 cycles of postoperative enfortumab vedotin + pembrolizumab, followed by 8 cycles of pembrolizumab alone. Each cycle is 21 days.

Drug: Enfortumab Vedotin

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Also known as: KEYTRUDA®, MK-3475

Arm A: Pembrolizumab + Surgery

Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) PROCEDURE

Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.

Arm A: Pembrolizumab + Surgery; Arm B: Surgery alone

Enfortumab Vedotin DRUG

Enfortumab vedotin 1.25 mg/kg by intravenous (IV) infusion, given on Days 1 and 8 of each 21-day cycle.

Also known as: Padcev, ASG-22CE, ASG-22ME

Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically confirmed diagnosis of urothelial carcinoma/muscle-invasive bladder cancer \[MIBC\] (cT2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology to be confirmed by Blinded Independent Central Review (BICR) (central pathology and/or imaging).
• Clinically nonmetastatic bladder cancer determined by imaging
• Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
• Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria OR be eligible for treatment with cisplatin but decline treatment with cisplatin-based chemotherapy:
• Impaired renal function with measured or calculated creatinine clearance (CrCl) 30 to 59 mL/min (calculated by Cockcroft-Gault method, Modification of Diet of Renal Disease \[MDRD\] equations, or measured by 24-hour urine collection)
• Eastern Cooperative Oncology Group (ECOG) Performance Status 2
• Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
• New York Heart Association (NYHA) Class III heart failure
• Transurethral resection (TUR) of a bladder tumor that is submitted for central pathology assessment and adequate to determine urothelial histology and PD-L1 expression assessment
• ECOG performance status of 0, 1, or 2
• Adequate organ function
• A male participant is eligible to participate if he agrees to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If the male participants are receiving pembrolizumab only or undergoing surgery only, there are no contraception requirements
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to use a highly effective contraceptive method or be abstinent from heterosexual intercourse (as their preferred and usual lifestyle) during the intervention period and for at least 120 days after the last dose of pembrolizumab and at least 180 days after the last dose of enfortumab vedotin; whichever comes last. A female participant must agree not to donate eggs during this period as well
• A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention

You may not qualify if:

• Known additional nonurothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions
• Has ≥ N2 or metastatic disease (M1) as identified by imaging
• Received any prior systemic treatment, chemoradiation, and/or radiation therapy for muscle-invasive bladder cancer (MIBC) or non-muscle invasive bladder cancer (NMIBC)
• Received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Received prior systemic anticancer therapy including investigational agents within 3 years prior to randomization
• Received any prior radiotherapy to the bladder
• Received a partial cystectomy of the bladder to remove any non-muscle-invasive bladder cancer (NMIBC) or MIBC
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
• Ongoing sensory or motor neuropathy Grade 2 or higher
• Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
• Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
• Severe hypersensitivity (≥ Grade 3) to enfortumab vedotin or any excipient contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations. Participants with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator
• Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Seagen Inc.: collaborator
• Astellas Pharma Global Development, Inc.: collaborator

Study Sites (242)

University of South Alabama, Mitchell Cancer Institute ( Site 1582)

Mobile, Alabama, 36604, United States

Location

CARTI Cancer Center ( Site 1577)

Little Rock, Arkansas, 72205, United States

Location

St. Joseph Heritage Healthcare ( Site 0046)

Fullerton, California, 92835, United States

Location

Scripps MD Anderson ( Site 0010)

La Jolla, California, 92037, United States

Location

Hoag Memorial Hospital Presbyterian ( Site 1595)

Newport Beach, California, 92663, United States

Location

John Wayne Cancer Institute ( Site 0075)

Santa Monica, California, 90404, United States

Location

University of Colorado Hospital ( Site 0098)

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center ( Site 0022)

Washington D.C., District of Columbia, 20007, United States

Location

Emory School of Medicine ( Site 0006)

Atlanta, Georgia, 30322, United States

Location

John H. Stroger Jr. Hospital of Cook County ( Site 1551)

Chicago, Illinois, 60612, United States

Location

University of Chicago ( Site 0068)

Chicago, Illinois, 60637, United States

Location

Parkview Cancer Institute ( Site 0077)

Fort Wayne, Indiana, 46845, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center ( Site 0004)

Indianapolis, Indiana, 46202, United States

Location

Wichita Urology Group ( Site 0059)

Wichita, Kansas, 67226, United States

Location

Tulane University School of Medicine ( Site 0088)

New Orleans, Louisiana, 70112, United States

Location

New England Cancer Specialists ( Site 0070)

Westbrook, Maine, 04092, United States

Location

Greater Baltimore Medical Center ( Site 0014)

Baltimore, Maryland, 21204, United States

Location

Dana-Farber Cancer Institute ( Site 1596)

Boston, Massachusetts, 02215, United States

Location

M Health Fairview Ridges Hospital ( Site 1555)

Burnsville, Minnesota, 55337, United States

Location

Morristown Medical Center ( Site 0015)

Morristown, New Jersey, 07960, United States

Location

UNM Comprehensive Cancer Center-Clinical Research Office ( Site 0045)

Albuquerque, New Mexico, 87106, United States

Location

Northwell Health - Monter Cancer Center ( Site 0083)

Lake Success, New York, 11042, United States

Location

New York University Perlmutter Cancer Center ( Site 0008)

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 0031)

New York, New York, 10029, United States

Location

Cleveland Clinic Main ( Site 1576)

Cleveland, Ohio, 44195, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0021)

Tulsa, Oklahoma, 74146, United States

Location

Providence Portland Medical Center [Portland, OR] ( Site 0095)

Portland, Oregon, 97213, United States

Location

MidLantic Urology ( Site 0089)

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Abramson Cancer Center of the University of Pennsylvania ( Site 0074)

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University ( Site 1579)

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center ( Site 0055)

Philadelphia, Pennsylvania, 19111, United States

Location

Allegheny General Hospital ( Site 0048)

Pittsburgh, Pennsylvania, 15212, United States

Location

Bon Secours St. Francis Health System ( Site 1572)

Greenville, South Carolina, 29607, United States

Location

Carolina Urologic Research Center ( Site 0062)

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Associates [Nashville, TN] ( Site 0053)

Nashville, Tennessee, 37209, United States

Location

Vanderbilt University Medical Center ( Site 0017)

Nashville, Tennessee, 37232, United States

Location

Texas Oncology-Baylor Sammons Cancer Center ( Site 1552)

Dallas, Texas, 75246, United States

Location

Inova Schar Cancer Institute ( Site 0007)

Fairfax, Virginia, 22031, United States

Location

Charleston Area Medical Center ( Site 0023)

Charleston, West Virginia, 25304, United States

Location

Asociación de Beneficencia Hospital Sirio Libanés ( Site 2102)

Buenos Aires, Buenos Aires F.D., C1419AHN, Argentina

Location

Western Sydney Local Health District ( Site 1259)

Blacktown, New South Wales, 2148, Australia

Location

Macquarie University ( Site 1251)

Macquarie Park, New South Wales, 2109, Australia

Location

Cairns Base Hospital ( Site 1257)

Cairns, Queensland, 4870, Australia

Location

Mater Misericordiae Ltd ( Site 1258)

South Brisbane, Queensland, 4101, Australia

Location

Eastern Health ( Site 1255)

Box Hill, Victoria, 3128, Australia

Location

Monash Health ( Site 1260)

Clayton, Victoria, 3168, Australia

Location

UCL Saint-Luc - Oncologie Medicale ( Site 0357)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

Location

CHU UCL Namur Site de Godinne ( Site 0354)

Yvoir, Namur, 5530, Belgium

Location

AZ Maria Middelares Gent ( Site 0353)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven ( Site 0361)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

AZ Sint-Jan Brugge ( Site 0352)

Bruges, West-Vlaanderen, 8000, Belgium

Location

AZ Delta vzw-Oncology ( Site 0362)

Roeselare, West-Vlaanderen, 8800, Belgium

Location

Arthur J.E. Child Comprehensive Cancer Centre ( Site 0100)

Calgary, Alberta, T2N 5G2, Canada

Location

BC Cancer Vancouver-Clinical Trials Unit ( Site 0121)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Silverado Resarch Inc. ( Site 0111)

Victoria, British Columbia, V8T 2C1, Canada

Location

Moncton Hospital - Horizon Health Network ( Site 0112)

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Sunnybrook Research Institute ( Site 0110)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0107)

Toronto, Ontario, M5G 2M9, Canada

Location

CIUSSS du Saguenay-Lac-St-Jean ( Site 0116)

Chicoutimi, Quebec, G7H 5H6, Canada

Location

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0105)

Montreal, Quebec, H1T 2M4, Canada

Location

Jewish General Hospital ( Site 0120)

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University Health Centre ( Site 0123)

Montreal, Quebec, H4A 3J1, Canada

Location

CIUSSS de l'Estrie-CHUS ( Site 0106)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Fundacion Colombiana de Cancerología Clinica Vida ( Site 2003)

Medellín, Antioquia, 050030, Colombia

Location

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2002)

Bogotá, Bogota D.C., 111321, Colombia

Location

IMAT S.A.S ( Site 2001)

Montería, Departamento de Córdoba, 230002, Colombia

Location

Fundación Cardiovascular de Colombia ( Site 2004)

Piedecuesta, Santander Department, 681017, Colombia

Location

Fundacion Valle del Lili- CIC-Fundacion Valle del Lili ( Site 2005)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Rigshospitalet University Hospital ( Site 0411)

Copenhagen, Capital Region, 2100, Denmark

Location

Herlev og Gentofte Hospital. ( Site 0412)

Herlev, Capital Region, 2730, Denmark

Location

Aarhus University Hospital Skejby ( Site 0418)

Aarhus, Central Jutland, 8200, Denmark

Location

Odense Universitetshospital ( Site 0413)

Odense, Region Syddanmark, 5000, Denmark

Location

Hopital de la Timone ( Site 0489)

Marseille, Bouches-du-Rhone, 13005, France

Location

Centre Georges Francois Leclerc ( Site 0488)

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

Centre Francois Baclesse ( Site 0459)

Caen, Calvados, 14075, France

Location

CHU Jean Minjoz ( Site 0455)

Besançon, Doubs, 25000, France

Location

Institut de Cancerologie du Gard - CHU Caremeau ( Site 0490)

Nîmes, Gard, 30029, France

Location

CHU de Bordeaux- Hopital Saint Andre ( Site 0456)

Bordeaux, Gironde, 33000, France

Location

Institut Claudius Regaud IUCT Oncopole ( Site 0486)

Toulouse, Haute-Garonne, 31059, France

Location

CHU de Montpellier - Hopital Saint-Eloi ( Site 0469)

Montpellier, Herault, 34295, France

Location

C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0492)

Rennes, Ille-et-Vilaine, 35033, France

Location

CHU Hotel Dieu Nantes ( Site 0458)

Nantes, Loire-Atlantique, 44093, France

Location

Hopital Belle Isle ( Site 0452)

Vantoux, Moselle, 57070, France

Location

C.H.U. Lyon Sud ( Site 0466)

Pierre-Bénite, Rhone, 69310, France

Location

Institut Gustave Roussy ( Site 0487)

Villejuif, Val-de-Marne, 94800, France

Location

CHU Cochin ( Site 0475)

Paris, 75014, France

Location

Hopital Europeen Georges Pompidou ( Site 0476)

Paris, 75015, France

Location

Hopital Bichat du Paris ( Site 0462)

Paris, 75018, France

Location

Klinikum Stuttgart - Katharinenhospital ( Site 0520)

Stuttgart, Baden-Wurttemberg, 70174, Germany

Location

Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0549)

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitaetsklinikum Erlangen ( Site 0546)

Erlangen, Bavaria, 91058, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern ( Site 0548)

Munich, Bavaria, 81377, Germany

Location

Universitaetsklinikum Wuerzburg ( Site 0547)

Würzburg, Bavaria, 97080, Germany

Location

Universitaetsklinikum Bonn ( Site 0550)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Carl Gustav Carus ( Site 0532)

Dresden, Saxony, 01307, Germany

Location

Universitaetsklinikum Magdeburg A.o.R. ( Site 0535)

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

SRH Wald-Klinikum Gera-Zentrum für klinische Studien ( Site 0533)

Gera, Thuringia, 07548, Germany

Location

Vivantes Klinikum am Urban ( Site 0529)

Berlin, 10967, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0528)

Hamburg, 20246, Germany

Location

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010)

Szeged, Csongrád megye, 6720, Hungary

Location

Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 1001)

Budapest, 1106, Hungary

Location

Debreceni Egyetem Klinikai Kozpont ( Site 1006)

Debrecen, 4032, Hungary

Location

Petz Aladar Megyei Oktato Korhaz ( Site 1012)

Győr, 9023, Hungary

Location

Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1007)

Kaposvár, 7400, Hungary

Location

Tallaght University Hospital ( Site 0734)

Dublin, D24 NR0A, Ireland

Location

University Hospital Waterford ( Site 0747)

Waterford, X91ER8E, Ireland

Location

Ha Emek Medical Center ( Site 0843)

Afula, 1834111, Israel

Location

Soroka Medical Center ( Site 0849)

Beersheba, 8410101, Israel

Location

Rambam Health Care Campus-Oncology Division ( Site 0845)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center ( Site 0842)

Jerusalem, 9103102, Israel

Location

Hadassah Ein Kerem Medical Center ( Site 0841)

Jerusalem, 9112001, Israel

Location

Meir Medical Center ( Site 0846)

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center ( Site 0847)

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center ( Site 0844)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 0850)

Tel Aviv, 6423906, Israel

Location

Yitzhak Shamir Medical Center. ( Site 0848)

Ẕerifin, 70300, Israel

Location

Policlinico Gemelli di Roma ( Site 0558)

Roma, Abruzzo, 00168, Italy

Location

Azienda Sanitaria Ospedaliera S Luigi Gonzaga-SCDU Oncologia Medica ( Site 0563)

Orbassano, Piedmont, 10043, Italy

Location

AULSS8 Berica-Ospedale S.Bortolo-ONCOLOGIA CLINICA ( Site 0562)

Vicenza, Veneto, 36100, Italy

Location

Azienda USL 8 di Arezzo-Medical Oncology ( Site 0565)

Arezzo, 52100, Italy

Location

A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico ( Site 0559)

Catania, 95123, Italy

Location

Ospedale San Raffaele-Oncologia Medica ( Site 0561)

Milan, 20132, Italy

Location

Istituto Nazionale Studio e Cura dei Tumori ( Site 0551)

Milan, 20133, Italy

Location

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori ( Site 0552)

Napoli, 80131, Italy

Location

Fondazione Salvatore Maugeri IRCCS ( Site 0554)

Pavia, 27100, Italy

Location

Azienda Ospedaliera Santa Maria Terni-S.C. Oncologia Medica e Traslazionale ( Site 0564)

Terni, 05100, Italy

Location

National Cancer Center Hospital East ( Site 2305)

Kashiwa, Chiba, 277-8577, Japan

Location

University of Tsukuba Hospital ( Site 2302)

Tsukuba, Ibaraki, 305-8576, Japan

Location

St. Marianna University Hospital ( Site 2321)

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kitasato University Hospital ( Site 2306)

Sagamihara, Kanagawa, 252-0375, Japan

Location

Yokosuka Kyosai Hospital ( Site 2307)

Yokosuka, Kanagawa, 238-8558, Japan

Location

Tohoku University Hospital ( Site 2301)

Sendai, Miyagi, 980-8574, Japan

Location

Nagano Municipal Hospital ( Site 2309)

Tomitake, Nagano, 381-8551, Japan

Location

Nara Medical University Hospital ( Site 2312)

Kashihara, Nara, 634-0813, Japan

Location

Osaka Rosai Hospital ( Site 2320)

Sakai, Osaka, 591-8025, Japan

Location

Saitama Prefectural Cancer Center ( Site 2319)

Ina-machi, Saitama, 362-0806, Japan

Location

Dokkyo Medical University Saitama Medical Center ( Site 2304)

Koshigaya, Saitama, 3438555, Japan

Location

Hamamatsu University Hospital ( Site 2311)

Hamamatsu, Shizuoka, 431-3192, Japan

Location

Institute of Science Tokyo Hospital ( Site 2303)

Bunkyō, Tokyo, 113-8519, Japan

Location

Toranomon Hospital ( Site 2322)

Minato-ku, Tokyo, 105-8470, Japan

Location

Toyama University Hospital ( Site 2308)

Toyoma, Toyama, 930-0194, Japan

Location

Gifu University Hospital ( Site 2310)

Gifu, 501-1112, Japan

Location

Kagoshima University Hospital ( Site 2317)

Kagoshima, 890-8520, Japan

Location

Nagasaki University Hospital ( Site 2315)

Nagasaki, 852-8501, Japan

Location

University Malaya Medical Centre ( Site 1702)

Lembah Pantai, Kuala Lumpur, 59100, Malaysia

Location

Hospital Pulau Pinang ( Site 1703)

George Town, Pulau Pinang, 10990, Malaysia

Location

Sarawak General Hospital ( Site 1701)

Kuching, Sarawak, 93586, Malaysia

Location

Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 0253)

Monterrey, Nuevo León, 66269, Mexico

Location

Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V. ( Site 0300)

Aguascalientes, 20010, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua ( Site 0254)

Chihuahua City, 31000, Mexico

Location

Centro de Tratamiento de Cancer ( Site 0266)

Metepec, 52140, Mexico

Location

Hospital Angeles Roma ( Site 0262)

Mexico City, 06700, Mexico

Location

Instituto Nacional de Cancerologia. ( Site 0256)

Mexico City, 14080, Mexico

Location

THE MEDICAL CITY ILOILO ( Site 1756)

Iloilo City, Iloilo, 5000, Philippines

Location

The Medical City ( Site 1752)

Pasig, National Capital Region, 1605, Philippines

Location

St. Luke s Medical Center ( Site 1751)

Quezon City, National Capital Region, 1112, Philippines

Location

Clinical Research Center Medic-R ( Site 1073)

Poznan, Greater Poland Voivodeship, 60-848, Poland

Location

Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 1068)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

Location

Szpital Wojewodzki ( Site 1062)

Tarnów, Lesser Poland Voivodeship, 33-100, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 1063)

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Europejskie Centrum Zdrowia Otwock ( Site 1058)

Otwock, Masovian Voivodeship, 05-400, Poland

Location

Luxmed Onkologia sp. z o. o. ( Site 1051)

Warsaw, Masovian Voivodeship, 01-748, Poland

Location

Bialostockie Centrum Onkologii ( Site 1072)

Bialystok, Podlaskie Voivodeship, 15-027, Poland

Location

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 1057)

Słupsk, Pomeranian Voivodeship, 76-200, Poland

Location

Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1061)

Bielsko-Biala, Silesian Voivodeship, 43-300, Poland

Location

Clinic of Bashkortostan State Medical University ( Site 0873)

Ufa, Baskortostan, Respublika, 450081, Russia

Location

Ivanovo Regional Oncology Dispensary ( Site 0852)

Ivanovo, Ivanovo Oblast, 153040, Russia

Location

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0861)

Krasnoyarsk, Krasnoyarsk Krai, 660133, Russia

Location

Kursk Regional Clinical Oncology Dispensary ( Site 0854)

Kursk, Kursk Oblast, 305524, Russia

Location

Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 0878)

Moscow, Moscow, 115478, Russia

Location

First Moscow State Medical University n.a. I.M.Sechenov ( Site 0884)

Moscow, Moscow, 119991, Russia

Location

Central Clinical Hospital with outpatient Clinic ( Site 0856)

Moscow, Moscow, 121359, Russia

Location

Bayandin Murmansk Regional Clinical Hospital ( Site 0859)

Murmansk, Murmansk Oblast, 183057, Russia

Location

Volga District Medical Center Federal Medical and Biological Agency ( Site 0857)

Nizhny Novgorod, Nizhny Novgorod Oblast, 603074, Russia

Location

Omsk Clinical Oncology Dispensary ( Site 0865)

Omsk, Omsk Oblast, 644013, Russia

Location

Leningrad Regional Oncology Center ( Site 0868)

Saint Petersburg, Sankt-Peterburg, 188663, Russia

Location

Clinical Hospital Saint Luka ( Site 0867)

Saint Petersburg, Sankt-Peterburg, 194044, Russia

Location

First St. Petersburg State Medical University n.a. acad. I.P. Pavlov ( Site 0872)

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0860)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0866)

Saratov, Saratov Oblast, 410012, Russia

Location

Sverdlovsk Regional Oncology Hospital ( Site 0874)

Yekaterinburg, Sverdlovsk Oblast, 620036, Russia

Location

Medical Sanitary Unit Neftyannik ( Site 0888)

Tyumen, Tyumen Oblast, 625000, Russia

Location

National University Hospital ( Site 1802)

Singapore, Central Singapore, 119074, Singapore

Location

Tan Tock Seng Hospital ( Site 1804)

Singapore, Central Singapore, 398442, Singapore

Location

Steve Biko Academic Hospital-Medical Oncology ( Site 1601)

Pretoria, Gauteng, 0001, South Africa

Location

Groote Schuur Hospital ( Site 1602)

Cape Town, Western Cape, 7925, South Africa

Location

National Cancer Center ( Site 1354)

Goyang-si, Kyonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital ( Site 1356)

Seongnam-si, Kyonggi-do, 13620, South Korea

Location

Asan Medical Center ( Site 1355)

Songpagu, Seoul, 05505, South Korea

Location

Kyungpook National University Chilgok Hospital-Urology ( Site 1357)

Deagu, Taegu-Kwangyokshi, 41404, South Korea

Location

Korea University Anam Hospital ( Site 1351)

Seoul, 02841, South Korea

Location

Seoul National University Hospital ( Site 1352)

Seoul, 03080, South Korea

Location

Samsung Medical Center ( Site 1353)

Seoul, 06351, South Korea

Location

Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0675)

Badalona, Barcelona, 08916, Spain

Location

Hospital Clinic i Provincial ( Site 0674)

Barcelona, Catalonia, 08036, Spain

Location

Hospital San Pedro de Alcantara ( Site 0697)

Cáceres, Extremadura, 10003, Spain

Location

Institut Català d'Oncologia (ICO) - Girona ( Site 0700)

Girona, Gerona, 17007, Spain

Location

Hospital Universitario Quiron Madrid ( Site 0694)

Pozuelo de Alarcón, Madrid, Comunidad de, 28223, Spain

Location

Instituto Valenciano de Oncologia - IVO ( Site 0679)

Valencia, Valenciana, Comunitat, 46009, Spain

Location

Hospital del Mar ( Site 0698)

Barcelona, 08003, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 0691)

Madrid, 28034, Spain

Location

Hospital Universitario San Carlos ( Site 0678)

Madrid, 28040, Spain

Location

Hospital Universitario la Paz ( Site 0690)

Madrid, 28046, Spain

Location

Hospital de Nuestra Senora de Valme ( Site 0693)

Seville, 41014, Spain

Location

Laenssjukhuset Ryhov ( Site 1215)

Jönköping, Jönköping County, 551 85, Sweden

Location

Karolinska Universitetssjukhuset Solna ( Site 1212)

Stockholm, Stockholm County, 171 76, Sweden

Location

Akademiska Sjukhuset ( Site 1211)

Uppsala, Uppsala County, 751 85, Sweden

Location

Cancercentrum ( Site 1214)

Umeå, Västerbotten County, 901 85, Sweden

Location

Onkologiska kliniken ( Site 1217)

Gothenburg, Västra Götaland County, 413 45, Sweden

Location

Ramathibodi Hospital. ( Site 1451)

Bangkok, Bangkok, 10400, Thailand

Location

Faculty of Medicine Siriraj Hospital ( Site 1452)

Bangkok, Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiangmai Hospital ( Site 1453)

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital ( Site 1454)

Khon Kaen, 40002, Thailand

Location

Hacettepe Universitesi Tıp Fakultesi ( Site 0931)

Ankara, 06100, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0930)

Istanbul, 34096, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0926)

Istanbul, 34722, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0921)

Istanbul, 34899, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0929)

Konya, 42080, Turkey (Türkiye)

Location

Sakarya Universitesi Tip Fakultesi ( Site 0933)

Sakarya, 54290, Turkey (Türkiye)

Location

Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi ( Site 0924)

Trabzon, 61080, Turkey (Türkiye)

Location

Cherkasy Regional Oncology Dispensary ( Site 0959)

Cherkasy, Cherkasy Oblast, 18009, Ukraine

Location

MNPE City Clinical Hospital #4 of Dnipro Regional Council ( Site 0951)

Dnipro, Dnipropetrovsk Oblast, 49102, Ukraine

Location

ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 0963)

Dnipropetrovsk, Dnipropetrovsk Oblast, 49005, Ukraine

Location

Regional Oncology Center of Kharkiv ( Site 0958)

Kharkiv, Kharkivs’ka Oblast’, 61000, Ukraine

Location

MNPE V.I. Shapoval Regional Medical Clinical Urology and Nephrology Center of KharkivRegCouncil ( Site 0969)

Kharkiv, Kharkivs’ka Oblast’, 61037, Ukraine

Location

Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0973)

Kharkiv, Kharkivs’ka Oblast’, 61166, Ukraine

Location

Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( Site 0976)

Antonivka Village, Kherson Oblast, 73000, Ukraine

Location

SNPE National Cancer Institute ( Site 0962)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

MNPE Lviv Regional Clinical Hospital of Lviv Regional Council ( Site 0955)

Lviv, Lviv Oblast, 79010, Ukraine

Location

Lviv State Regional Oncological Center ( Site 0967)

Lviv, Lviv Oblast, 79031, Ukraine

Location

Zhytomyr Regional Oncology Center ( Site 0971)

Zhytomyr, Zhytomyr Oblast, 10002, Ukraine

Location

Kyiv City Clinical Oncology Center ( Site 0960)

Kyiv, 03115, Ukraine

Location

Walsall Manor Hospital-Oncology ( Site 0743)

Walsall, Devon, WS2 9PS, United Kingdom

Location

Kent and Canterbury Hospital ( Site 0733)

Canterbury, England, CT1 3NG, United Kingdom

Location

The James Cook University Hospital ( Site 0730)

Middlesbrough, England, TS4 3BW, United Kingdom

Location

Imperial College Healthcare NHS Trust ( Site 0745)

London, Hammersmith and Fulham, W6 8RF, United Kingdom

Location

Lister Hospital ( Site 0739)

Stevenage, Hertfordshire, SG1 4AB, United Kingdom

Location

Barts Health NHS Trust - St Bartholomew s Hospital ( Site 0725)

London, London, City of, EC1A 7BE, United Kingdom

Location

The Royal Marsden Foundation Trust ( Site 0726)

London, London, City of, SW3 6JJ, United Kingdom

Location

Western General Hospital ( Site 0749)

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

Clatterbridge Oncology Centre ( Site 0731)

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Royal Cornwall Hospital ( Site 0727)

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (1)

• Galsky MD, Hoimes CJ, Necchi A, Shore N, Witjes JA, Steinberg G, Bedke J, Nishiyama H, Fang X, Kataria R, Sbar E, Jia X, Siefker-Radtke A. Perioperative pembrolizumab therapy in muscle-invasive bladder cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303. Future Oncol. 2021 Aug;17(24):3137-3150. doi: 10.2217/fon-2021-0273. Epub 2021 May 19.

  PMID: 34008425 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab; Surgical Procedures, Operative; Cystectomy; enfortumab vedotin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: April 23, 2019
• Study Start: July 24, 2019
• Primary Completion: June 6, 2025
• Study Completion (Estimated): December 15, 2027
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

MY (3); AR (1); SG (2); ZA (2); DE (11); JP (18); TU (7); BE (6); CA (11); SE (5); PL (9); RU (17); AU (6); IE (2); PH (3); KR (7); UA (12); GB (10); ES (11); ME (6); DK (4); US (39); CO (5); FR (16); HU (5); IT (10); TH (4); IL (10)