AzTrials
AzTrials

Urinary Bladder Cancer, Muscle-invasivePhase 3NCT03924895

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)

A Phase 3 study testing Pembrolizumab, Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) and Enfortumab Vedotin in people with Urinary Bladder Cancer, Muscle-invasive, run by Merck Sharp & Dohme LLC at 242 sites in 28 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urinary Bladder Cancer, Muscle-invasive
What is being tested?
Pembrolizumab, Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) and Enfortumab Vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
595 participants
Where
242 sitesin 28 countries
Study dates
24 Jul 2019to 15 Dec 2027
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • Has uncontrolled diabetes
  • History of (noninfectious) pneumonitis that required steroids, or current pneumonitis
  • Active infection requiring systemic therapy
  • Has had an allogeneic tissue/solid organ transplant

Trial locations and contacts

242 sites in 28 countries.

242 sites in 28 countries

United States39 sites

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

    Albuquerque, New Mexico, 87106

  • Emory School of Medicine ( Site 0006)

    Atlanta, Georgia, 30322

  • University of Colorado Hospital ( Site 0098)

    Aurora, Colorado, 80045

  • MidLantic Urology ( Site 0089)

    Bala-Cynwyd, Pennsylvania, 19004

  • Greater Baltimore Medical Center ( Site 0014)

    Baltimore, Maryland, 21204

  • Dana-Farber Cancer Institute ( Site 1596)

    Boston, Massachusetts, 02215

  • M Health Fairview Ridges Hospital ( Site 1555)

    Burnsville, Minnesota, 55337

  • Charleston Area Medical Center ( Site 0023)

    Charleston, West Virginia, 25304

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

    Chicago, Illinois, 60612

  • University of Chicago ( Site 0068)

    Chicago, Illinois, 60637

  • Cleveland Clinic Main ( Site 1576)

    Cleveland, Ohio, 44195

  • Texas Oncology-Baylor Sammons Cancer Center ( Site 1552)

    Dallas, Texas, 75246

  • Inova Schar Cancer Institute ( Site 0007)

    Fairfax, Virginia, 22031

  • Parkview Cancer Institute ( Site 0077)

    Fort Wayne, Indiana, 46845

  • St. Joseph Heritage Healthcare ( Site 0046)

    Fullerton, California, 92835

  • Bon Secours St. Francis Health System ( Site 1572)

    Greenville, South Carolina, 29607

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

    Indianapolis, Indiana, 46202

  • Scripps MD Anderson ( Site 0010)

    La Jolla, California, 92037

  • Northwell Health - Monter Cancer Center ( Site 0083)

    Lake Success, New York, 11042

  • CARTI Cancer Center ( Site 1577)

    Little Rock, Arkansas, 72205

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

    Mobile, Alabama, 36604

  • Morristown Medical Center ( Site 0015)

    Morristown, New Jersey, 07960

  • Carolina Urologic Research Center ( Site 0062)

    Myrtle Beach, South Carolina, 29572

  • Urology Associates [Nashville, TN] ( Site 0053)

    Nashville, Tennessee, 37209

  • Vanderbilt University Medical Center ( Site 0017)

    Nashville, Tennessee, 37232

  • Tulane University School of Medicine ( Site 0088)

    New Orleans, Louisiana, 70112

  • New York University Perlmutter Cancer Center ( Site 0008)

    New York, New York, 10016

  • Icahn School of Medicine at Mount Sinai ( Site 0031)

    New York, New York, 10029

  • Hoag Memorial Hospital Presbyterian ( Site 1595)

    Newport Beach, California, 92663

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

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University ( Site 1579)

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center ( Site 0055)

    Philadelphia, Pennsylvania, 19111

  • Allegheny General Hospital ( Site 0048)

    Pittsburgh, Pennsylvania, 15212

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

    Portland, Oregon, 97213

  • John Wayne Cancer Institute ( Site 0075)

    Santa Monica, California, 90404

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

    Tulsa, Oklahoma, 74146

  • Georgetown University Medical Center ( Site 0022)

    Washington D.C., District of Columbia, 20007

  • New England Cancer Specialists ( Site 0070)

    Westbrook, Maine, 04092

  • Wichita Urology Group ( Site 0059)

    Wichita, Kansas, 67226

Other trials in United States

Japan18 sites

  • Institute of Science Tokyo Hospital ( Site 2303)

    Bunkyō, Tokyo, 113-8519

  • Gifu University Hospital ( Site 2310)

    Gifu, 501-1112

  • Hamamatsu University Hospital ( Site 2311)

    Hamamatsu, Shizuoka, 431-3192

  • Saitama Prefectural Cancer Center ( Site 2319)

    Ina-machi, Saitama, 362-0806

  • Kagoshima University Hospital ( Site 2317)

    Kagoshima, 890-8520

  • Nara Medical University Hospital ( Site 2312)

    Kashihara, Nara, 634-0813

  • National Cancer Center Hospital East ( Site 2305)

    Kashiwa, Chiba, 277-8577

  • St. Marianna University Hospital ( Site 2321)

    Kawasaki, Kanagawa, 216-8511

  • Dokkyo Medical University Saitama Medical Center ( Site 2304)

    Koshigaya, Saitama, 3438555

  • Toranomon Hospital ( Site 2322)

    Minato-ku, Tokyo, 105-8470

  • Nagasaki University Hospital ( Site 2315)

    Nagasaki, 852-8501

  • Kitasato University Hospital ( Site 2306)

    Sagamihara, Kanagawa, 252-0375

  • Osaka Rosai Hospital ( Site 2320)

    Sakai, Osaka, 591-8025

  • Tohoku University Hospital ( Site 2301)

    Sendai, Miyagi, 980-8574

  • Nagano Municipal Hospital ( Site 2309)

    Tomitake, Nagano, 381-8551

  • Toyama University Hospital ( Site 2308)

    Toyoma, Toyama, 930-0194

  • University of Tsukuba Hospital ( Site 2302)

    Tsukuba, Ibaraki, 305-8576

  • Yokosuka Kyosai Hospital ( Site 2307)

    Yokosuka, Kanagawa, 238-8558

Other trials in Japan

Russia17 sites

  • Ivanovo Regional Oncology Dispensary ( Site 0852)

    Ivanovo, Ivanovo Oblast, 153040

  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0861)

    Krasnoyarsk, Krasnoyarsk Krai, 660133

  • Kursk Regional Clinical Oncology Dispensary ( Site 0854)

    Kursk, Kursk Oblast, 305524

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

    Moscow, Moscow, 115478

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

    Moscow, Moscow, 119991

  • Central Clinical Hospital with outpatient Clinic ( Site 0856)

    Moscow, Moscow, 121359

  • Bayandin Murmansk Regional Clinical Hospital ( Site 0859)

    Murmansk, Murmansk Oblast, 183057

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

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603074

  • Omsk Clinical Oncology Dispensary ( Site 0865)

    Omsk, Omsk Oblast, 644013

  • Leningrad Regional Oncology Center ( Site 0868)

    Saint Petersburg, Sankt-Peterburg, 188663

  • Clinical Hospital Saint Luka ( Site 0867)

    Saint Petersburg, Sankt-Peterburg, 194044

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

    Saint Petersburg, Sankt-Peterburg, 197022

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

    Saint Petersburg, Sankt-Peterburg, 197758

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

    Saratov, Saratov Oblast, 410012

  • Medical Sanitary Unit Neftyannik ( Site 0888)

    Tyumen, Tyumen Oblast, 625000

  • Clinic of Bashkortostan State Medical University ( Site 0873)

    Ufa, Baskortostan, Respublika, 450081

  • Sverdlovsk Regional Oncology Hospital ( Site 0874)

    Yekaterinburg, Sverdlovsk Oblast, 620036

Other trials in Russia

France16 sites

  • CHU Jean Minjoz ( Site 0455)

    Besançon, Doubs, 25000

  • CHU de Bordeaux- Hopital Saint Andre ( Site 0456)

    Bordeaux, Gironde, 33000

  • Centre Francois Baclesse ( Site 0459)

    Caen, Calvados, 14075

  • Centre Georges Francois Leclerc ( Site 0488)

    Dijon, Bourgogne-Franche-Comté, 21000

  • Hopital de la Timone ( Site 0489)

    Marseille, Bouches-du-Rhone, 13005

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

    Montpellier, Herault, 34295

  • CHU Hotel Dieu Nantes ( Site 0458)

    Nantes, Loire-Atlantique, 44093

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

    Nîmes, Gard, 30029

  • CHU Cochin ( Site 0475)

    Paris, 75014

  • Hopital Europeen Georges Pompidou ( Site 0476)

    Paris, 75015

  • Hopital Bichat du Paris ( Site 0462)

    Paris, 75018

  • C.H.U. Lyon Sud ( Site 0466)

    Pierre-Bénite, Rhone, 69310

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

    Rennes, Ille-et-Vilaine, 35033

  • Institut Claudius Regaud IUCT Oncopole ( Site 0486)

    Toulouse, Haute-Garonne, 31059

  • Hopital Belle Isle ( Site 0452)

    Vantoux, Moselle, 57070

  • Institut Gustave Roussy ( Site 0487)

    Villejuif, Val-de-Marne, 94800

Other trials in France

Ukraine12 sites

  • MNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of CRC" ( Site 0959)

    Cherkasy, Cherkasy Oblast, 18009

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

    Dnipro, Dnipropetrovsk Oblast, 49102

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

    Dnipropetrovsk, Dnipropetrovsk Oblast, 49005

  • Regional Oncology Center of Kharkiv ( Site 0958)

    Kharkiv, Kharkiv Oblast, 61000

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

    Kharkiv, Kharkiv Oblast, 61037

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

    Kharkiv, Kharkiv Oblast, 61166

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

    Kherson, Kherson Oblast, 73034

  • SNPE National Cancer Institute ( Site 0962)

    Kyiv, Kyivska Oblast, 03022

  • Kyiv City Clinical Oncology Center ( Site 0960)

    Kyiv, 03115

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

    Lviv, Lviv Oblast, 79010

  • Lviv State Regional Oncological Center ( Site 0967)

    Lviv, Lviv Oblast, 79031

  • Zhytomyr Regional Oncology Center ( Site 0971)

    Zhytomyr, Zhytomyr Oblast, 10002

Other trials in Ukraine

Canada11 sites

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

    Calgary, Alberta, T2N 5G2

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

    Chicoutimi, Quebec, G7H 5H6

  • Moncton Hospital - Horizon Health Network ( Site 0112)

    Moncton, New Brunswick, E1C 6Z8

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

    Montreal, Quebec, H1T 2M4

  • Jewish General Hospital ( Site 0120)

    Montreal, Quebec, H3T 1E2

  • McGill University Health Centre ( Site 0123)

    Montreal, Quebec, H4A 3J1

  • CIUSSS de l'Estrie-CHUS ( Site 0106)

    Sherbrooke, Quebec, J1H 5N4

  • Sunnybrook Research Institute ( Site 0110)

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre ( Site 0107)

    Toronto, Ontario, M5G 2M9

  • BC Cancer Vancouver-Clinical Trials Unit ( Site 0121)

    Vancouver, British Columbia, V5Z 4E6

  • Silverado Resarch Inc. ( Site 0111)

    Victoria, British Columbia, V8T 2C1

Other trials in Canada

Germany11 sites

  • Vivantes Klinikum am Urban ( Site 0529)

    Berlin, 10967

  • Universitaetsklinikum Bonn ( Site 0550)

    Bonn, North Rhine-Westphalia, 53127

  • Universitaetsklinikum Carl Gustav Carus ( Site 0532)

    Dresden, Saxony, 01307

  • Universitaetsklinikum Erlangen ( Site 0546)

    Erlangen, Bavaria, 91058

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

    Gera, Thuringia, 07548

  • Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0528)

    Hamburg, 20246

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

    Magdeburg, Saxony-Anhalt, 39120

  • Klinikum der Universitaet Muenchen - Grosshadern ( Site 0548)

    Munich, Bavaria, 81377

  • Klinikum Stuttgart - Katharinenhospital ( Site 0520)

    Stuttgart, Baden-Wurttemberg, 70174

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

    Tübingen, Baden-Wurttemberg, 72076

  • Universitaetsklinikum Wuerzburg ( Site 0547)

    Würzburg, Bavaria, 97080

Other trials in Germany

Spain11 sites

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

    Badalona, Barcelona, 08916

  • Hospital Clinic i Provincial ( Site 0674)

    Barcelona, Catalonia, 08036

  • Hospital del Mar ( Site 0698)

    Barcelona, 08003

  • Hospital San Pedro de Alcantara ( Site 0697)

    Cáceres, Extremadura, 10003

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

    Girona, Gerona, 17007

  • Hospital Universitario Ramon y Cajal ( Site 0691)

    Madrid, 28034

  • Hospital Universitario San Carlos ( Site 0678)

    Madrid, 28040

  • Hospital Universitario la Paz ( Site 0690)

    Madrid, 28046

  • Hospital Universitario Quiron Madrid ( Site 0694)

    Pozuelo de Alarcón, Madrid, Comunidad de, 28223

  • Hospital de Nuestra Senora de Valme ( Site 0693)

    Seville, 41014

  • Instituto Valenciano de Oncologia - IVO ( Site 0679)

    Valencia, Valenciana, Comunitat, 46009

Other trials in Spain

Israel10 sites

  • Ha Emek Medical Center ( Site 0843)

    Afula, 1834111

  • Soroka Medical Center ( Site 0849)

    Beersheba, 8410101

  • Rambam Health Care Campus-Oncology Division ( Site 0845)

    Haifa, 3109601

  • Shaare Zedek Medical Center ( Site 0842)

    Jerusalem, 9103102

  • Hadassah Ein Kerem Medical Center ( Site 0841)

    Jerusalem, 9112001

  • Meir Medical Center ( Site 0846)

    Kfar Saba, 4428164

  • Rabin Medical Center ( Site 0847)

    Petah Tikva, 4941492

  • Sheba Medical Center ( Site 0844)

    Ramat Gan, 5265601

  • Sourasky Medical Center ( Site 0850)

    Tel Aviv, 6423906

  • Yitzhak Shamir Medical Center. ( Site 0848)

    Tsrifin, 7033001

Other trials in Israel

Italy10 sites

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

    Arezzo, 52100

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

    Catania, 95123

  • Ospedale San Raffaele-Oncologia Medica ( Site 0561)

    Milan, 20132

  • Istituto Nazionale Studio e Cura dei Tumori ( Site 0551)

    Milan, 20133

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

    Naples, 80131

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

    Orbassano, Piedmont, 10043

  • Fondazione Salvatore Maugeri IRCCS ( Site 0554)

    Pavia, 27100

  • Policlinico Gemelli di Roma ( Site 0558)

    Roma, Abruzzo, 00168

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

    Terni, 05100

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

    Vicenza, Veneto, 36100

Other trials in Italy

United Kingdom10 sites

  • Kent and Canterbury Hospital ( Site 0733)

    Canterbury, England, CT1 3NG

  • Western General Hospital ( Site 0749)

    Edinburgh, Midlothian, EH4 2XU

  • Imperial College Healthcare NHS Trust ( Site 0745)

    London, Hammersmith and Fulham, W6 8RF

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

    London, London, City of, EC1A 7BE

  • The Royal Marsden Foundation Trust ( Site 0726)

    London, London, City of, SW3 6JJ

  • Clatterbridge Oncology Centre ( Site 0731)

    Metropolitan Borough of Wirral, CH63 4JY

  • The James Cook University Hospital ( Site 0730)

    Middlesbrough, England, TS4 3BW

  • Lister Hospital ( Site 0739)

    Stevenage, Hertfordshire, SG1 4AB

  • Royal Cornwall Hospital ( Site 0727)

    Truro, TR1 3LJ

  • Walsall Manor Hospital-Oncology ( Site 0743)

    Walsall, Devon, WS2 9PS

Other trials in United Kingdom

Poland9 sites

  • Bialostockie Centrum Onkologii ( Site 1072)

    Bialystok, Podlaskie Voivodeship, 15-027

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

    Bielsko-Biala, Silesian Voivodeship, 43-300

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

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Europejskie Centrum Zdrowia Otwock ( Site 1058)

    Otwock, Masovian Voivodeship, 05-400

  • Clinical Research Center Medic-R ( Site 1073)

    Poznan, Greater Poland Voivodeship, 60-848

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

    Słupsk, Pomeranian Voivodeship, 76-200

  • Szpital Wojewodzki ( Site 1062)

    Tarnów, Lesser Poland Voivodeship, 33-100

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

    Warsaw, Masovian Voivodeship, 01-748

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

    Wroclaw, Lower Silesian Voivodeship, 50-556

Other trials in Poland

South Korea7 sites

  • Kyungpook National University Chilgok Hospital-Urology ( Site 1357)

    Deagu, Taegu-Kwangyokshi, 41404

  • National Cancer Center ( Site 1354)

    Goyang-si, Kyonggi-do, 10408

  • Seoul National University Bundang Hospital ( Site 1356)

    Seongnam-si, Kyonggi-do, 13620

  • Korea University Anam Hospital ( Site 1351)

    Seoul, 02841

  • Seoul National University Hospital ( Site 1352)

    Seoul, 03080

  • Samsung Medical Center ( Site 1353)

    Seoul, 06351

  • Asan Medical Center ( Site 1355)

    Songpagu, Seoul, 05505

Other trials in South Korea

Turkey (Türkiye)7 sites

  • Hacettepe Universitesi Tıp Fakultesi ( Site 0931)

    Ankara, 06100

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0930)

    Istanbul, 34096

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

    Istanbul, 34722

  • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0921)

    Istanbul, 34899

  • Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0929)

    Konya, 42080

  • Sakarya Universitesi Tip Fakultesi ( Site 0933)

    Sakarya, 54290

  • Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi ( Site 0924)

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Australia6 sites

  • Western Sydney Local Health District ( Site 1259)

    Blacktown, New South Wales, 2148

  • Eastern Health ( Site 1255)

    Box Hill, Victoria, 3128

  • Cairns Base Hospital ( Site 1257)

    Cairns, Queensland, 4870

  • Monash Health ( Site 1260)

    Clayton, Victoria, 3168

  • Macquarie University ( Site 1251)

    Macquarie Park, New South Wales, 2109

  • Mater Misericordiae Ltd ( Site 1258)

    South Brisbane, Queensland, 4101

Other trials in Australia

Belgium6 sites

  • AZ Sint-Jan Brugge ( Site 0352)

    Bruges, West-Vlaanderen, 8000

  • AZ Maria Middelares Gent ( Site 0353)

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven ( Site 0361)

    Leuven, Vlaams-Brabant, 3000

  • AZ Delta vzw-Oncology ( Site 0362)

    Roeselare, West-Vlaanderen, 8800

  • UCL Saint-Luc - Oncologie Medicale ( Site 0357)

    St-Lambrechts-Woluwe, Bruxelles-Capitale, Region de, 1200

  • CHU UCL Namur Site de Godinne ( Site 0354)

    Yvoir, Namur, 5530

Other trials in Belgium

Mexico6 sites

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

    Aguascalientes, 20010

  • Centro Estatal de Cancerologia de Chihuahua ( Site 0254)

    Chihuahua City, 31000

  • Centro de Tratamiento de Cancer ( Site 0266)

    Metepec, 52140

  • Hospital Angeles Roma ( Site 0262)

    Mexico City, 06700

  • Instituto Nacional de Cancerologia. ( Site 0256)

    Mexico City, 14080

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

    Monterrey, Nuevo León, 66269

Other trials in Mexico

Colombia5 sites

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

    Bogotá, Bogota D.C., 111321

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

    Cali, Valle del Cauca Department, 760032

  • Fundacion Colombiana de Cancerología Clinica Vida ( Site 2003)

    Medellín, Antioquia, 050030

  • IMAT S.A.S ( Site 2001)

    Montería, Departamento de Córdoba, 230002

  • Fundación Cardiovascular de Colombia ( Site 2004)

    Piedecuesta, Santander Department, 681017

Other trials in Colombia

Hungary5 sites

  • Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 1001)

    Budapest, 1106

  • Debreceni Egyetem Klinikai Kozpont ( Site 1006)

    Debrecen, Hajdú-Bihar, 4032

  • Petz Aladar Megyei Oktato Korhaz ( Site 1012)

    Győr, 9023

  • Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1007)

    Kaposvár, 7400

  • SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010)

    Szeged, Csongrád megye, 6720

Other trials in Hungary

Sweden5 sites

  • Onkologiska kliniken ( Site 1217)

    Gothenburg, Västra Götaland County, 413 45

  • Laenssjukhuset Ryhov ( Site 1215)

    Jönköping, Jönköping County, 551 85

  • Karolinska Universitetssjukhuset Solna ( Site 1212)

    Stockholm, Stockholm County, 171 76

  • Cancercentrum ( Site 1214)

    Umeå, Västerbotten County, 901 85

  • Akademiska Sjukhuset ( Site 1211)

    Uppsala, Uppsala County, 751 85

Other trials in Sweden

Denmark4 sites

  • Aarhus University Hospital Skejby ( Site 0418)

    Aarhus, Central Jutland, 8200

  • Rigshospitalet University Hospital ( Site 0411)

    Copenhagen, Capital Region, 2100

  • Herlev og Gentofte Hospital. ( Site 0412)

    Herlev, Capital Region, 2730

  • Odense Universitetshospital ( Site 0413)

    Odense, Region Syddanmark, 5000

Other trials in Denmark

Thailand4 sites

  • Ramathibodi Hospital. ( Site 1451)

    Bangkok, Bangkok, 10400

  • Faculty of Medicine Siriraj Hospital ( Site 1452)

    Bangkok, Bangkok, 10700

  • Maharaj Nakorn Chiangmai Hospital ( Site 1453)

    Chiang Mai, 50200

  • Srinagarind Hospital ( Site 1454)

    Khon Kaen, 40002

Other trials in Thailand

Malaysia3 sites

  • Hospital Pulau Pinang ( Site 1703)

    George Town, Pulau Pinang, 10990

  • Sarawak General Hospital ( Site 1701)

    Kuching, Sarawak, 93586

  • University Malaya Medical Centre ( Site 1702)

    Lembah Pantai, Kuala Lumpur, 59100

Other trials in Malaysia

Philippines3 sites

  • THE MEDICAL CITY ILOILO ( Site 1756)

    Iloilo City, Iloilo, 5000

  • The Medical City ( Site 1752)

    Pasig, National Capital Region, 1605

  • St. Luke s Medical Center ( Site 1751)

    Quezon City, National Capital Region, 1112

Other trials in Philippines

Ireland2 sites

  • Tallaght University Hospital ( Site 0734)

    Dublin, D24 NR0A

  • University Hospital Waterford ( Site 0747)

    Waterford, X91ER8E

Other trials in Ireland

Singapore2 sites

  • National University Hospital ( Site 1802)

    Singapore, Central Singapore, 119074

  • Tan Tock Seng Hospital ( Site 1804)

    Singapore, Central Singapore, 398442

Other trials in Singapore

South Africa2 sites

  • Groote Schuur Hospital ( Site 1602)

    Cape Town, Western Cape, 7925

  • Steve Biko Academic Hospital-Medical Oncology ( Site 1601)

    Pretoria, Gauteng, 0001

Other trials in South Africa

Argentina1 site

  • Asociación de Beneficencia Hospital Sirio Libanés ( Site 2102)

    Buenos Aires, Buenos Aires F.D., C1419AHN

Other trials in Argentina

About this study

Official title: A Randomized Phase 3 Study Evaluating Cystectomy With Perioperative Pembrolizumab and Cystectomy With Perioperative Enfortumab Vedotin and Pembrolizumab Versus Cystectomy Alone in Participants Who Are Cisplatin-Ineligible or Decline Cisplatin With Muscle-Invasive Bladder Cancer (KEYNOTE-905/EV-303)

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.

Read more

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.

Being tested
Pembrolizumab, Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]), Enfortumab Vedotin
Keywords
Muscle-Invasive Bladder Cancer (MIBC), Enfortumab vedotin (EV), Pembrolizumab (MK-3475)
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called KEYTRUDA®, MK-3475

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

  • Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])Procedure or surgery

    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.

  • Enfortumab VedotinDrug

    Also called Padcev, ASG-22CE, ASG-22ME

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

Study groups in NCT03924895
Study groupRoleWhat they receive
Arm A: Pembrolizumab + SurgeryExperimentalParticipants receive 3 preoperative cycles of pembrolizumab, followed by standard of care surgery, followed by 14 cycles of postoperative pembrolizumab. Each cycle is 21 days.
Receives: Drug: Pembrolizumab; Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Arm B: Surgery aloneActive comparatorParticipants receive standard of care surgery alone.
Receives: Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
Arm C: Enfortumab Vedotin + Pembrolizumab + SurgeryExperimentalParticipants 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.
Receives: Drug: Enfortumab Vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone

    EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy + pelvic lymph node dissection (RC + PLND) surgery, failure to undergo RC + PLND surgery in participants with residual disease and any radiographic disease present (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.

    Measured: Up to approximately 53 months

Secondary outcomes (11)

  1. EFS Between Arm A 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.

    Measured: Up to approximately 6.75 years

  2. Overall Survival (OS) Between Arm C and Arm B

    OS is defined as the time from randomization to death due to any cause.

    Measured: Up to approximately 7.6 years

  3. OS Between Arm A and Arm B

    OS is defined as the time from randomization to death due to any cause.

    Measured: Up to approximately 7.6 years

  4. Pathologic Complete Response (pCR) Rate Between Arm C and Arm B

    Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blind independent central review (BICR).

    Measured: Up to approximately 53 monhts

  5. pCR Rate Between Arm A and Arm B

    Pathologic complete response rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as determined centrally.

    Measured: Up to approximately 5.7 years

  6. Disease-Free Survival (DFS)

    DFS is defined as the time from first post-surgery baseline scan until:

    • local or distant recurrence as assessed by imaging and/or biopsy
    • Death due to any cause

    Measured: Up to approximately 6.75 years

  7. Pathologic Downstaging (pDS) Rate Between Arm A and Arm B

    Pathologic downstaging rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of <pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC and PLND.

    Measured: Up to approximately 5.7 years

  8. Pathologic Downstaging {pDS) Rate Between Arm C and Arm B

    Pathologic downstaging (pDS) is defined as participants with a tumor classification of <pT2. The pathologic stage <pT2 includes pT0 (No residual primary tumor found in the tissue examined), pTis (carcinoma in situ; a flat, non-invasive cancer confined to the epithelial lining), pTa (Non-invasive papillary carcinoma limited to the urothelium) pT1 (tumor has invaded the connective tissue beneath the urothelium, but not the muscle layer) and N0 (No cancer found in the examined lymph nodes) in examined tissue from RC and PLND. The <pT2 category represents a better outcome than participants with residual muscle-invasive disease (pT2 or higher) and/or any nodal involvement (N1/N2). The percentage of participants with pDS is presented.

    Measured: Up to approximately 53 months

  9. Number of Participants Experiencing Adverse Events (AEs)

    An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    Measured: Up to approximately 7.6 years

  10. Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs)

    An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    Measured: Up to approximately 1 year

  11. Number of Participants Experiencing Perioperative Complications

    The number of participants who experience perioperative complications will be presented.

    Measured: Up to approximately 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2019
  2. Study start24 Jul 2019
  3. Primary completion6 Jun 2025
  4. Study completion15 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
595 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03924895
Sponsor's protocol ID
3475-905
Other IDs
MK-3475-905, KEYNOTE-905, EV-303, PHRR210911-003890, jRCT2031220686, 2023-504932-16, 2031220686, U1111-1290-4057
Status last verified
Jun 2026
First submitted
22 Apr 2019
Last updated
30 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, Atduev V, Goger YE, Rausch S, Kang SH, Loriot Y, Bedke J, Galsky MD, O'Donnell PH, von Amsberg G, Alimohamed N, Sulimka G, Gupta S, Paramonov V, Nakane K, Mihm M, Meng C, Huang CD, Ramamurthy C, Homet Moreno B, Ullen A; KEYNOTE-905/EV-303 Investigators. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi: 10.1056/NEJMoa2511674. Epub 2026 Feb 18.

    PubMed 41707170

  • 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.

    PubMed 34008425

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]) and Enfortumab Vedotin in people with Urinary Bladder Cancer, Muscle-invasive, run by Merck Sharp & Dohme LLC at 242 sites in 28 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 242 sites in United States, Japan, Russia, France, Ukraine and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-Free Survival (EFS) Between Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery and Arm B: Surgery Alone (time frame: Up to approximately 53 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03924895, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in