Urinary Bladder Cancer, Muscle-invasive Clinical Trial
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)
| Verified date | May 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 857 |
| Est. completion date | December 15, 2027 |
| Est. primary completion date | May 31, 2027 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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 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 - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Asociación de Beneficencia Hospital Sirio Libanés ( Site 2102) | Buenos Aires | Caba |
| Australia | Western Sydney Local Health District ( Site 1259) | Blacktown | New South Wales |
| Australia | Eastern Health ( Site 1255) | Box Hill | Victoria |
| Australia | Cairns Base Hospital ( Site 1257) | Cairns | Queensland |
| Australia | Monash Health ( Site 1260) | Clayton | Victoria |
| Australia | Macquarie University ( Site 1251) | Macquarie Park | New South Wales |
| Australia | Mater Misericordiae Ltd ( Site 1258) | South Brisbane | Queensland |
| Belgium | AZ Sint-Jan Brugge ( Site 0352) | Brugge | West-Vlaanderen |
| Belgium | UCL Saint-Luc - Oncologie Medicale ( Site 0357) | Bruxelles | Bruxelles-Capitale, Region De |
| Belgium | AZ Maria Middelares Gent ( Site 0353) | Gent | Oost-Vlaanderen |
| Belgium | UZ Leuven ( Site 0361) | Leuven | Vlaams-Brabant |
| Belgium | AZ Delta vzw-Oncology ( Site 0362) | Roeselare | West-Vlaanderen |
| Belgium | CHU UCL Namur Site de Godinne ( Site 0354) | Yvoir | Namur |
| Canada | Tom Baker Cancer Centre ( Site 0100) | Calgary | Alberta |
| Canada | CIUSSS du Saguenay-Lac-St-Jean ( Site 0116) | Chicoutimi | Quebec |
| Canada | Moncton Hospital - Horizon Health Network ( Site 0112) | Moncton | New Brunswick |
| Canada | CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0105) | Montreal | Quebec |
| Canada | Jewish General Hospital ( Site 0120) | Montreal | Quebec |
| Canada | McGill University Health Centre ( Site 0123) | Montréal | Quebec |
| Canada | CIUSSS de l'Estrie-CHUS ( Site 0106) | Sherbrooke | Quebec |
| Canada | Princess Margaret Cancer Centre ( Site 0107) | Toronto | Ontario |
| Canada | Sunnybrook Research Institute ( Site 0110) | Toronto | Ontario |
| Canada | BC Cancer Vancouver-Clinical Trials Unit ( Site 0121) | Vancouver | British Columbia |
| Canada | Silverado Resarch Inc. ( Site 0111) | Victoria | British Columbia |
| Colombia | Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 2002) | Bogota | Distrito Capital De Bogota |
| Colombia | Fundacion Valle del Lili- CIC-Fundacion Valle del Lili ( Site 2005) | Cali | Valle Del Cauca |
| Colombia | Fundación Colombiana de Cancerología Clínica Vida ( Site 2003) | Medellin | Antioquia |
| Colombia | Oncomédica S.A.S ( Site 2001) | Montería | Cordoba |
| Colombia | Fundación Cardiovascular de Colombia ( Site 2004) | Piedecuesta | Santander |
| Denmark | Aarhus University Hospital Skejby ( Site 0418) | Aarhus | Midtjylland |
| Denmark | Herlev og Gentofte Hospital. ( Site 0412) | Herlev | Hovedstaden |
| Denmark | Rigshospitalet University Hospital ( Site 0411) | Kobenhavn | Hovedstaden |
| Denmark | Odense Universitetshospital ( Site 0413) | Odense | Syddanmark |
| France | CHU Jean Minjoz ( Site 0455) | Besancon | Doubs |
| France | CHU de Bordeaux- Hopital Saint Andre ( Site 0456) | Bordeaux | Gironde |
| France | Centre Francois Baclesse ( Site 0459) | Caen | Calvados |
| France | Centre Georges Francois Leclerc ( Site 0488) | Dijon | Cote-d Or |
| France | Hopital de la Timone ( Site 0489) | Marseille | Bouches-du-Rhone |
| France | CHU de Montpellier - Hopital Saint-Eloi ( Site 0469) | Montpellier | Languedoc-Roussillon |
| France | CHU Hotel Dieu Nantes ( Site 0458) | Nantes | Loire-Atlantique |
| France | Institut de Cancerologie du Gard - CHU Caremeau ( Site 0490) | Nimes | Gard |
| France | CHU Cochin ( Site 0475) | Paris | |
| France | Hopital Bichat du Paris ( Site 0462) | Paris | |
| France | Hopital Europeen Georges Pompidou ( Site 0476) | Paris | |
| France | C.H.U. Lyon Sud ( Site 0466) | Pierre Benite | Rhone |
| France | C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 0492) | Rennes | Ille-et-Vilaine |
| France | Institut Claudius Regaud IUCT Oncopole ( Site 0486) | Toulouse | Haute-Garonne |
| France | Hopital Belle Isle ( Site 0452) | Vantoux | Moselle |
| France | Institut Gustave Roussy ( Site 0487) | Villejuif | Val-de-Marne |
| Germany | Vivantes Klinikum am Urban ( Site 0529) | Berlin | |
| Germany | Universitaetsklinikum Bonn ( Site 0550) | Bonn | Nordrhein-Westfalen |
| Germany | Universitaetsklinikum Carl Gustav Carus ( Site 0532) | Dresden | Sachsen |
| Germany | Universitaetsklinikum Erlangen ( Site 0546) | Erlangen | Bayern |
| Germany | SRH Wald-Klinikum Gera-Zentrum für klinische Studien ( Site 0533) | Gera | Thuringen |
| Germany | Universitaetsklinikum Hamburg-Eppendorf-Onkologisches Zentrum ( Site 0528) | Hamburg | |
| Germany | Universitaetsklinikum Magdeburg A.o.R. ( Site 0535) | Magdeburg | Sachsen-Anhalt |
| Germany | Klinikum der Universitaet Muenchen - Grosshadern ( Site 0548) | Muenchen | Bayern |
| Germany | Klinikum Stuttgart - Katharinenhospital ( Site 0520) | Stuttgart | Baden-Wurttemberg |
| Germany | Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0549) | Tuebingen | Baden-Wurttemberg |
| Germany | Universitaetsklinikum Wuerzburg ( Site 0547) | Wuerzburg | Bayern |
| Hungary | Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 1001) | Budapest | |
| Hungary | Debreceni Egyetem Klinikai Kozpont ( Site 1006) | Debrecen | |
| Hungary | Petz Aladar Megyei Oktato Korhaz ( Site 1012) | Gyor | |
| Hungary | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1007) | Kaposvar | |
| Hungary | SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 1010) | Szeged | Csongrad |
| Ireland | Tallaght University Hospital ( Site 0734) | Dublin | |
| Ireland | University Hospital Waterford ( Site 0747) | Waterford | |
| Israel | Ha Emek Medical Center ( Site 0843) | Afula | |
| Israel | Soroka Medical Center ( Site 0849) | Beer Sheva | |
| Israel | Rambam Health Care Campus-Oncology Division ( Site 0845) | Haifa | |
| Israel | Hadassah Ein Kerem Medical Center ( Site 0841) | Jerusalem | |
| Israel | Shaare Zedek Medical Center ( Site 0842) | Jerusalem | |
| Israel | Meir Medical Center ( Site 0846) | Kfar Saba | |
| Israel | Rabin Medical Center ( Site 0847) | Petach Tikva | |
| Israel | Sheba Medical Center ( Site 0844) | Ramat Gan | |
| Israel | Sourasky Medical Center ( Site 0850) | Tel Aviv | |
| Israel | Yitzhak Shamir Medical Center. ( Site 0848) | Zerifin | |
| Italy | Azienda USL 8 di Arezzo-Medical Oncology ( Site 0565) | Arezzo | |
| Italy | A.O.U. Policlinico Vittorio Emanuele - Presidio Gaspare Rodolico ( Site 0559) | Catania | |
| Italy | Istituto Nazionale Studio e Cura dei Tumori ( Site 0551) | Milano | |
| Italy | Ospedale San Raffaele-Oncologia Medica ( Site 0561) | Milano | Lombardia |
| Italy | Istituto Nazionale Per Lo Studio E La Cura Dei Tumori ( Site 0552) | Napoli | |
| Italy | Azienda Sanitaria Ospedaliera S Luigi Gonzaga-SCDU Oncologia Medica ( Site 0563) | Orbassano | Piemonte |
| Italy | Fondazione Salvatore Maugeri IRCCS ( Site 0554) | Pavia | |
| Italy | Policlinico Gemelli di Roma ( Site 0558) | Roma | Abruzzo |
| Italy | Azienda Ospedaliera Santa Maria Terni-S.C. Oncologia Medica e Traslazionale ( Site 0564) | Terni | |
| Italy | AULSS8 Berica-Ospedale S.Bortolo-ONCOLOGIA CLINICA ( Site 0562) | Vicenza | Veneto |
| Japan | Tokyo Medical and Dental University Hospital ( Site 2303) | Bunkyo | Tokyo |
| Japan | Gifu University Hospital ( Site 2310) | Gifu | |
| Japan | Hamamatsu University Hospital ( Site 2311) | Hamamatsu | Shizuoka |
| Japan | Saitama Prefectural Cancer Center ( Site 2319) | Ina-machi | Saitama |
| Japan | Kagoshima University Hospital ( Site 2317) | Kagoshima | |
| Japan | Nara Medical University Hospital ( Site 2312) | Kashihara | Nara |
| Japan | National Cancer Center Hospital East ( Site 2305) | Kashiwa | Chiba |
| Japan | St. Marianna University Hospital ( Site 2321) | Kawasaki | Kanagawa |
| Japan | Dokkyo Medical University Saitama Medical Center ( Site 2304) | Koshigaya | Saitama |
| Japan | Toranomon Hospital ( Site 2322) | Minato-ku | Tokyo |
| Japan | Nagasaki University Hospital ( Site 2315) | Nagasaki | |
| Japan | Kitasato University Hospital ( Site 2306) | Sagamihara | Kanagawa |
| Japan | Osaka Rosai Hospital ( Site 2320) | Sakai | Osaka |
| Japan | Tohoku University Hospital ( Site 2301) | Sendai-shi | Miyagi |
| Japan | Nagano Municipal Hospital ( Site 2309) | Tomitake | Nagano |
| Japan | Toyama University Hospital ( Site 2308) | Toyoma | Toyama |
| Japan | Tsukuba University Hospital ( Site 2302) | Tsukuba | Ibaraki |
| Japan | Yokosukakyosai ( Site 2307) | Yokosuka | Kanagawa |
| Korea, Republic of | Kyungpook National University Chilgok Hospital-Urology ( Site 1357) | Deagu | Taegu-Kwangyokshi |
| Korea, Republic of | National Cancer Center ( Site 1354) | Goyang-si | Kyonggi-do |
| Korea, Republic of | Seoul National University Bundang Hospital ( Site 1356) | Seongnam-si | Kyonggi-do |
| Korea, Republic of | Korea University Anam Hospital ( Site 1351) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 1353) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 1352) | Seoul | |
| Korea, Republic of | Asan Medical Center ( Site 1355) | Songpagu | Seoul |
| Malaysia | Hospital Pulau Pinang ( Site 1703) | Georgetown | Pulau Pinang |
| Malaysia | Sarawak General Hospital ( Site 1701) | Kuching | Sarawak |
| Malaysia | University Malaya Medical Centre ( Site 1702) | Lembah Pantai | Kuala Lumpur |
| Mexico | Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V. ( Site 0300) | Aguascalientes | |
| Mexico | Centro Estatal de Cancerologia de Chihuahua ( Site 0254) | Chihuahua | |
| Mexico | Instituto Nacional de Cancerologia. ( Site 0256) | Ciudad de Mexico | |
| Mexico | Centro de Tratamiento de Cancer ( Site 0266) | Metepec | |
| Mexico | Hospital Angeles Roma ( Site 0262) | Mexico City | |
| Mexico | Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 0253) | Monterrey | Nuevo Leon |
| Philippines | THE MEDICAL CITY ILOILO ( Site 1756) | Iloilo City | Iloilo |
| Philippines | The Medical City ( Site 1752) | Pasig City | National Capital Region |
| Philippines | St. Luke s Medical Center ( Site 1751) | Quezon City | National Capital Region |
| Poland | Bialostockie Centrum Onkologii ( Site 1072) | Bialystok | Podlaskie |
| Poland | Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1061) | Bielsko-Biala | Slaskie |
| Poland | Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 1068) | Bydgoszcz | Kujawsko-pomorskie |
| Poland | Europejskie Centrum Zdrowia Otwock ( Site 1058) | Otwock | Mazowieckie |
| Poland | Clinical Research Center Medic-R ( Site 1073) | Poznan | Wielkopolskie |
| Poland | Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 1057) | Slupsk | Pomorskie |
| Poland | Szpital Wojewodzki ( Site 1062) | Tarnow | Malopolskie |
| Poland | Luxmed Onkologia sp. z o. o. ( Site 1051) | Warszawa | Mazowieckie |
| Poland | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 1063) | Wroclaw | Dolnoslaskie |
| Russian Federation | Sverdlovsk Regional Oncology Hospital ( Site 0874) | Ekaterinburg | Sverdlovskaya Oblast |
| Russian Federation | Ivanovo Regional Oncology Dispensary ( Site 0852) | Ivanovo | Ivanovskaya Oblast |
| Russian Federation | Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0861) | Krasnoyarsk | Krasnoyarskiy Kray |
| Russian Federation | Kursk Regional Clinical Oncology Dispensary ( Site 0854) | Kursk | Kurskaya Oblast |
| Russian Federation | Central Clinical Hospital with outpatient Clinic ( Site 0856) | Moscow | Moskva |
| Russian Federation | First Moscow State Medical University n.a. I.M.Sechenov ( Site 0884) | Moscow | Moskva |
| Russian Federation | Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 0878) | Moscow | Moskva |
| Russian Federation | Bayandin Murmansk Regional Clinical Hospital ( Site 0859) | Murmansk | Murmanskaya Oblast |
| Russian Federation | Volga District Medical Center Federal Medical and Biological Agency ( Site 0857) | Nizhny Novgorod | Nizhegorodskaya Oblast |
| Russian Federation | Omsk Clinical Oncology Dispensary ( Site 0865) | Omsk | Omskaya Oblast |
| Russian Federation | Leningrad Regional Oncology Center ( Site 0868) | Saint Petersburg | Sankt-Peterburg |
| Russian Federation | First St. Petersburg State Medical University n.a. acad. I.P. Pavlov ( Site 0872) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0860) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | Saratov State Medical University n.a. V.I.Razumovskiy ( Site 0866) | Saratov | Saratovskaya Oblast |
| Russian Federation | Clinical Hospital Saint Luka ( Site 0867) | St. Petersburg | Sankt-Peterburg |
| Russian Federation | Medical Sanitary Unit Neftyannik ( Site 0888) | Tyumen | Tyumenskaya Oblast |
| Russian Federation | Clinic of Bashkortostan State Medical University ( Site 0873) | Ufa | Baskortostan, Respublika |
| Singapore | National University Hospital ( Site 1802) | Singapore | Central Singapore |
| Singapore | Tan Tock Seng Hospital ( Site 1804) | Singapore | Central Singapore |
| South Africa | Groote Schuur Hospital ( Site 1602) | Cape Town | Western Cape |
| South Africa | Steve Biko Academic Hospital-Medical Oncology ( Site 1601) | Pretoria | Gauteng |
| Spain | Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0675) | Badalona | Barcelona |
| Spain | Hospital Clinic i Provincial ( Site 0674) | Barcelona | Cataluna |
| Spain | Hospital del Mar ( Site 0698) | Barcelona | |
| Spain | Hospital San Pedro de Alcantara ( Site 0697) | Caceres | Extremadura |
| Spain | Institut Català d'Oncologia (ICO) - Girona ( Site 0700) | Girona | Gerona |
| Spain | Hospital Universitario la Paz ( Site 0690) | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal ( Site 0691) | Madrid | |
| Spain | Hospital Universitario San Carlos ( Site 0678) | Madrid | |
| Spain | Hospital Universitario Quiron Madrid ( Site 0694) | Pozuelo de Alarcon | Madrid, Comunidad De |
| Spain | Hospital de Nuestra Senora de Valme ( Site 0693) | Sevilla | |
| Spain | Instituto Valenciano de Oncologia - IVO ( Site 0679) | Valencia | Valenciana, Comunitat |
| Sweden | Onkologiska kliniken ( Site 1217) | Goteborg | Vastra Gotalands Lan |
| Sweden | Laenssjukhuset Ryhov ( Site 1215) | Jonkoping | Jonkopings Lan |
| Sweden | Karolinska Universitetssjukhuset Solna ( Site 1212) | Stockholm | Stockholms Lan |
| Sweden | Cancercentrum ( Site 1214) | Umea | Vasterbottens Lan |
| Sweden | Akademiska Sjukhuset ( Site 1211) | Uppsala | Uppsala Lan |
| Thailand | Faculty of Medicine Siriraj Hospital ( Site 1452) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Ramathibodi Hospital. ( Site 1451) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Maharaj Nakorn Chiangmai Hospital ( Site 1453) | Chiang Mai | |
| Thailand | Srinagarind Hospital ( Site 1454) | Khon Kaen | |
| Turkey | Hacettepe Universitesi Tip Fakultesi ( Site 0931) | Ankara | |
| Turkey | Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0930) | Istanbul | |
| Turkey | Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0921) | Istanbul | |
| Turkey | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0926) | Istanbul | |
| Turkey | Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0929) | Konya | |
| Turkey | Sakarya Universitesi Tip Fakultesi ( Site 0933) | Sakarya | |
| Turkey | Karadeniz Teknik Universitesi Tip Fakultesi Farabi Hastanesi ( Site 0924) | Trabzon | |
| Ukraine | Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( | Antonivka Village | Khersonska Oblast |
| Ukraine | Cherkasy Regional Oncology Dispensary ( Site 0959) | Cherkasy | Cherkaska Oblast |
| Ukraine | MNPE City Clinical Hospital #4 of Dnipro Regional Council ( Site 0951) | Dnipro | Dnipropetrovska Oblast |
| Ukraine | ME ?.?. Mechnykov Dnipro Regional Clinical Hospital ( Site 0963) | Dnipropetrovsk | Dnipropetrovska Oblast |
| Ukraine | MNPE V.I. Shapoval Regional Medical Clinical Urology and Nephrology Center of KharkivRegCouncil ( Si | Kharkiv | Kharkivska Oblast |
| Ukraine | Municipal Non-profit Enterprise of Kharkiv Regional Council RCSDRPP ( Site 0973) | Kharkiv | Kharkivska Oblast |
| Ukraine | Regional Oncology Center of Kharkiv ( Site 0958) | Kharkiv | Kharkivska Oblast |
| Ukraine | Kyiv City Clinical Oncology Center ( Site 0960) | Kyiv | |
| Ukraine | SNPE National Cancer Institute ( Site 0962) | Kyiv | Kyivska Oblast |
| Ukraine | Lviv State Regional Oncological Center ( Site 0967) | Lviv | Lvivska Oblast |
| Ukraine | MNPE Lviv Regional Clinical Hospital of Lviv Regional Council ( Site 0955) | Lviv | Lvivska Oblast |
| Ukraine | Zhytomyr Regional Oncology Center ( Site 0971) | Zhytomyr | Zhytomyrska Oblast |
| United Kingdom | Kent and Canterbury Hospital ( Site 0733) | Canterbury | England |
| United Kingdom | Western General Hospital ( Site 0749) | Edinburgh | Midlothian |
| United Kingdom | Barts Health NHS Trust - St Bartholomew s Hospital ( Site 0725) | London | London, City Of |
| United Kingdom | Imperial College Healthcare NHS Trust ( Site 0745) | London | London, City Of |
| United Kingdom | The Royal Marsden Foundation Trust ( Site 0726) | London | London, City Of |
| United Kingdom | The James Cook University Hospital ( Site 0730) | Middlesbrough | England |
| United Kingdom | Lister Hospital ( Site 0739) | Stevenage | Hertfordshire |
| United Kingdom | Royal Cornwall Hospital ( Site 0727) | Truro | |
| United Kingdom | Walsall Manor Hospital-Oncology ( Site 0743) | Walsall | |
| United Kingdom | Clatterbridge Oncology Centre ( Site 0731) | Wirral | |
| United States | UNM Comprehensive Cancer Center-Clinical Research Office ( Site 0045) | Albuquerque | New Mexico |
| United States | Emory School of Medicine ( Site 0006) | Atlanta | Georgia |
| United States | University of Colorado Hospital ( Site 0098) | Aurora | Colorado |
| United States | MidLantic Urology ( Site 0089) | Bala-Cynwyd | Pennsylvania |
| United States | Greater Baltimore Medical Center ( Site 0014) | Baltimore | Maryland |
| United States | Dana-Farber Cancer Institute ( Site 1596) | Boston | Massachusetts |
| United States | M Health Fairview Ridges Hospital ( Site 1555) | Burnsville | Minnesota |
| United States | Charleston Area Medical Center ( Site 0023) | Charleston | West Virginia |
| United States | John H. Stroger Jr. Hospital of Cook County ( Site 1551) | Chicago | Illinois |
| United States | University of Chicago ( Site 0068) | Chicago | Illinois |
| United States | Cleveland Clinic Main ( Site 1576) | Cleveland | Ohio |
| United States | Texas Oncology-Baylor Sammons Cancer Center ( Site 1552) | Dallas | Texas |
| United States | Inova Schar Cancer Institute ( Site 0007) | Fairfax | Virginia |
| United States | Parkview Cancer Institute ( Site 0077) | Fort Wayne | Indiana |
| United States | St. Joseph Heritage Healthcare ( Site 0046) | Fullerton | California |
| United States | Bon Secours St. Francis Health System ( Site 1572) | Greenville | South Carolina |
| United States | Indiana University Melvin and Bren Simon Comprehensive Cancer Center ( Site 0004) | Indianapolis | Indiana |
| United States | Scripps MD Anderson ( Site 0010) | La Jolla | California |
| United States | Northwell Health - Monter Cancer Center ( Site 0083) | Lake Success | New York |
| United States | CARTI Cancer Center ( Site 1577) | Little Rock | Arkansas |
| United States | University of South Alabama, Mitchell Cancer Institute ( Site 1582) | Mobile | Alabama |
| United States | Morristown Medical Center ( Site 0015) | Morristown | New Jersey |
| United States | Carolina Urologic Research Center ( Site 0062) | Myrtle Beach | South Carolina |
| United States | Urology Associates [Nashville, TN] ( Site 0053) | Nashville | Tennessee |
| United States | Vanderbilt University Medical Center ( Site 0017) | Nashville | Tennessee |
| United States | Tulane University School of Medicine ( Site 0088) | New Orleans | Louisiana |
| United States | Icahn School of Medicine at Mount Sinai ( Site 0031) | New York | New York |
| United States | New York University Perlmutter Cancer Center ( Site 0008) | New York | New York |
| United States | Hoag Memorial Hospital Presbyterian ( Site 1595) | Newport Beach | California |
| United States | Abramson Cancer Center of the University of Pennsylvania ( Site 0074) | Philadelphia | Pennsylvania |
| United States | Fox Chase Cancer Center ( Site 0055) | Philadelphia | Pennsylvania |
| United States | Thomas Jefferson University ( Site 1579) | Philadelphia | Pennsylvania |
| United States | Allegheny General Hospital ( Site 0048) | Pittsburgh | Pennsylvania |
| United States | Providence Portland Medical Center [Portland, OR] ( Site 0095) | Portland | Oregon |
| United States | John Wayne Cancer Institute ( Site 0075) | Santa Monica | California |
| United States | New England Cancer Specialists ( Site 0070) | Scarborough | Maine |
| United States | Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0021) | Tulsa | Oklahoma |
| United States | Georgetown University Medical Center ( Site 0022) | Washington | District of Columbia |
| United States | Wichita Urology Group ( Site 0059) | Wichita | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC | Astellas Pharma Global Development, Inc., Seagen Inc. |
United States, Argentina, Australia, Belgium, Canada, Colombia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Thailand, Turkey, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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, 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 7.7 years | |
| Secondary | 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, 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 7.7 years | |
| Secondary | Overall Survival (OS) between Arm C and Arm B | OS is defined as the time from randomization to death due to any cause. | Up to approximately 8.4 years | |
| Secondary | OS between Arm A and Arm B | OS is defined as the time from randomization to death due to any cause. | Up to approximately 8.4 years | |
| Secondary | 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 determined centrally. | Up to approximately 5.7 years | |
| Secondary | 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. | Up to approximately 5.7 years | |
| Secondary | 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 |
Up to approximately 7.7 years | |
| Secondary | 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 | Up to approximately 5.7 years |
| |
| Secondary | pDS Rate between Arm C 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 | Up to approximately 5.7 years |
| |
| Secondary | 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. | Up to approximately 8.4 years | |
| Secondary | 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. | Up to approximately 1 year | |
| Secondary | Number of Participants Experiencing Perioperative Complications | The number of participants who experience perioperative complications will be presented. | Up to approximately 1 year |