Studie bezpečnosti a účinnosti různých kombinací avelumabu jako terapie u lokálně pokročilého nebo metastatického uroteliálního karcinomu (JAVELIN Medley močového měchýře)
10. srpna 2026 aktualizováno: EMD Serono Research & Development Institute, Inc.
Fáze II, multicentrická, randomizovaná, otevřená studie s paralelním ramenem, deštníková studie avelumabu (MSB0010718C) v kombinaci s jinými protinádorovými látkami jako udržovací léčba u účastníků s lokálně pokročilým nebo metastatickým uroteliálním karcinomem, jejichž onemocnění u první linie platiny nepostupovalo - obsahující chemoterapii (JAVELIN Medley močového měchýře)
Účelem této studie je posoudit bezpečnost a účinnost avelumabu v kombinaci s jinými protinádorovými činidly jako udržovací léčby u účastníků s rakovinou močového měchýře.
Přehled studie
Postavení
Aktivní, ne nábor
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
256
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Bedford Park, Austrálie
- Flinders Medical Centre
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Footscray, Austrálie
- Sunshine Hospital - PARENT
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Kurralta Park, Austrálie
- Ashford Cancer Centre Research
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Liverpool, Austrálie
- Liverpool Hospital - PARENT
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Newcastle, Austrálie
- Calvary Mater Newcastle - PARENT
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Southport, Austrálie
- Tasman Oncology Research Ltd - Oncology
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Sydney, Austrálie
- Macquarie University Hospital - PARENT
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Westmead, Austrálie
- The Kinghorn Can Cen
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Antwerp, Belgie
- ZNA Middelheim - Middelheim - account 2
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Brasschaat, Belgie
- AZ Klina - PARENT
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Brussels, Belgie
- Institut Jules Bordet - Medical Oncology
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Ghent, Belgie
- Universitair Ziekenhuis Gent - Medical Oncology
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Kortrijk, Belgie
- AZ Groeninge - Campus Kennedylaan - account 2
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Libramont, Belgie
- Centre Hospitalier de l'Ardenne - PARENT
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Liège, Belgie
- CHU de Liège - PARENT
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Wuerzburg, Belgie
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Angers, Francie
- ICO - Site Paul Papin - service d'oncologie medicale
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Bordeaux, Francie
- Institut Bergonié - Service d'Oncologie Médicale
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Caen, Francie
- Centre François Baclesse - Pathologies Gynecologiques
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Créteil, Francie
- Hôpital Henri Mondor - Service d'Oncologie Médicale
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Le Mans, Francie
- Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
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Lyon, Francie
- Centre Leon Berard - Service d'Oncologie Medicale
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Marseille, Francie
- Hôpital de la Timone - service d'urologie
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Nîmes, Francie
- Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
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Paris, Francie
- Hôpital Cochin - Hematologie et Oncologie Médicale
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Poitiers, Francie
- CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
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Rennes, Francie
- CRLCC Eugene Marquis - Service d'Oncologie médicale
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Saint-Herblain, Francie
- ICO - Site René Gauducheau - Service d'Oncologie medicale
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Strasbourg, Francie
- Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
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Strasbourg, Francie
- Clinique Sainte-Anne - Service d'Oncologie Médicale
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Hauts De Seine
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Suresnes, Hauts De Seine, Francie, 92151
- Hôpital Foch - Service d'Oncologie Médicale
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Bologna, Itálie
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
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Florence, Itálie
- Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
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Forlì, Itálie
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
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Milan, Itálie
- Ospedale San Raffaele - U.O. di Oncologia Medica
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Milan, Itálie
- Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
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Misterbianco, Itálie
- Humanitas Istituto Clinico Catanese - Oncologia Medica
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Naples, Itálie
- Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
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Naples, Itálie
- Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
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Padova, Itálie
- IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
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Pisa, Itálie
- Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
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Ravenna, Itálie
- Ospedale Santa Maria delle Croci
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Rome, Itálie
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
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San Giovanni Rotondo, Itálie
- IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
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Terni, Itálie
- Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
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Daejeon, Jižní Korea
- Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
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Gyeonggi-do, Jižní Korea
- National Cancer Center
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Seongnam-si, Jižní Korea
- Seoul National University Bundang Hospital
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Seoul, Jižní Korea
- Asan Medical Center
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Seoul, Jižní Korea
- Samsung Medical Center
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Seoul, Jižní Korea
- Seoul National University Hospital
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Seoul, Jižní Korea
- Severance Hospital, Yonsei University Health System
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Seoul, Jižní Korea
- The Catholic University of Korea, Seoul St. Mary's Hospital
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Brampton, Kanada
- William Osler Health System - Brampton Civic Hospital
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Greenfield Park, Kanada
- CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
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Montreal, Kanada
- CHUM Centre de Recherche
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Ottawa, Kanada
- The Ottawa Hospital Cancer Centre
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Essen, Německo
- Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
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Frankfurt, Německo
- Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
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Halle, Německo
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Mönchengladbach, Německo
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Münster, Německo
- Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
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Tübingen, Německo
- Universitaetsklinikum Tuebingen - Klinik fuer Urologie
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North Rhine-Westphalia
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Muenchen, North Rhine-Westphalia, Německo, 41063
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Saxony-Anhalt
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Halle, Saxony-Anhalt, Německo, 0044384
- Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
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Manchester, Spojené království
- The Christie Hospital - Dept of Oncology
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Preston, Spojené království
- Royal Preston Hospital - Rosemere Cancer Centre
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Greater London
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London, Greater London, Spojené království, 0024514
- Barts Hospital - Dept of Medical Oncology
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Idaho
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Coeur d'Alene, Idaho, Spojené státy, 83814
- Beacon Cancer Care
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Kansas
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Kansas City, Kansas, Spojené státy, 66205
- University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
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Maryland
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Baltimore, Maryland, Spojené státy, 21287
- The Johns Hopkins Hospital
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Baltimore, Maryland, Spojené státy, 21287-7049
- Johns Hopkins University
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Missouri
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Kansas City, Missouri, Spojené státy, 66204
- AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center
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Washington
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Seattle, Washington, Spojené státy, 98109
- Seattle Cancer Care Alliance
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Tacoma, Washington, Spojené státy, 98405
- Multicare Health System Tacoma General Hospital
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Wisconsin
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Madison, Wisconsin, Spojené státy, 53706
- University of Wisconsin Cancer Center
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Kaohsiung City, Tchaj-wan
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Kaohsiung City, Tchaj-wan
- Kaohsiung Chang Gung Memorial Hospital
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Taichung, Tchaj-wan
- China Medical University Hospital
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Tainan, Tchaj-wan
- Chi Mei Hospital, Liouying
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Taipei, Tchaj-wan
- National Taiwan University Hospital
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Taipei, Tchaj-wan
- Taipei Veterans General Hospital
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Taoyuan, Tchaj-wan
- Chang Gung Memorial Hospital,Linkou
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Athens, Řecko
- General Hospital of Athens "Alexandra"
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Athens, Řecko
- University General Hospital "Attikon"
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Athens, Řecko
- Athens Medical Center
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Thessaloniki, Řecko
- EUROMEDICA General Clinic of Thessaloniki
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Badajoz, Španělsko
- Hospital Infanta Cristina - Unidad de Fase I
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Barcelona, Španělsko
- Hospital del Mar - Servicio de Oncologia
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Barcelona, Španělsko
- Hospital de la Santa Creu i Sant Pau - Dept of Oncology
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Barcelona, Španělsko
- Hospital Clinic de Barcelona - Servicio de Oncologia
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Barcelona, Španělsko
- Hospital Universitario Virgen del Rocio - Oncology Service
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Córdoba, Španělsko
- Hospital Universitario Reina Sofia - Dept of Oncology
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Elche, Španělsko
- Hospital General Universitario de Elche - Servicio de Oncologia
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Lugo, Španělsko
- Hospital Universitario Lucus Augusti - Oncology
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Madrid, Španělsko
- Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
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Manresa, Španělsko
- ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Popis
Kritéria pro zařazení:
- Účastníci s histologicky potvrzeným, neresekabilním lokálně pokročilým nebo metastazujícím uroteliálním karcinomem. Histologie přechodných buněk i smíšená histologie přechodných/nepřechodných buněk jsou povoleny, ale převládající histologií musí být karcinom přechodných buněk
- Účastníci zdokumentovali stadium IIIA/IIIB s N1-N3 nebo onemocnění stadia IV (podle American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis system, 8. vydání) na začátku chemoterapie první linie.
- Poslední dávka chemoterapie první linie musí být podána nejméně 4 týdny a ne více než 10 týdnů před randomizací v této studii
- Předpokládaná životnost minimálně 3 měsíce
- Účastníci bez progresivního onemocnění podle pokynů RECIST v1.1 po dokončení 4 až 6 cyklů 1litrové chemoterapie. Způsobilost založená na tomto kritériu bude určena zkoušejícím přezkoumáním radiologických hodnocení před chemoterapií a po chemoterapii (skenování CT/MRI).
- Stav výkonnosti (PS) Eastern Cooperative Oncology Group (ECOG) 0 nebo 1
- Přiměřená hematologická, jaterní a renální funkce, jak je definováno v protokolu
- Mohou platit jiná kritéria pro zařazení definovaná protokolem
Kritéria vyloučení:
- Účastníci s předchozí imunoterapií interleukinem-2 (IL-2), IL-15, interferonem alfa (IFN-α) nebo receptorem proti programované smrti-1 (PD-1), ligandem proti programované smrti 1 (PD-L1 ), anti PD-L2, anti CD137 nebo cytotoxická T lymfocytární protilátka-4 (CTLA-4) (včetně ipilimumabu), anti TROP2, jakákoli jiná protilátka nebo lék specificky zacílený na kostimulaci T lymfocytů nebo imunitní kontrolní body nebo na kteroukoli z hodnocené léky používané v kombinaci s avelumabem.
- Účastníci s aktivní infekcí 48 hodin před randomizací vyžadující systémovou léčbu
- Účastníci se známou předchozí nebo suspektní přecitlivělostí na studované léky nebo jakoukoli složku v jejich formulacích
- Účastníci s předchozí adjuvantní nebo neoadjuvantní systémovou terapií do 12 měsíců od randomizace
- Účastníci s očkováním do 4 týdnů od první dávky studijní léčby a během zkoušky je zakázáno s výjimkou podávání inaktivovaných vakcín (například inaktivovaných vakcín proti chřipce) a vakcín proti koronaviru s deficitem replikace schválených nebo povolených místními zdravotnickými úřady
- Mohou platit jiná kritéria vyloučení definovaná protokolem
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Avelumab
Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Ostatní jména:
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Experimentální: Avelumab + Sacituzumab Govitecan (SG)
Participants received intravenous infusion of Avelumab at a dose of 800 milligrams (mg) once every 2 weeks in combination with intravenous infusion of SG at dose of 10 milligrams per kilogram (mg/kg) of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Ostatní jména:
Participants received intravenous infusion SG at dose of 10 mg/kg of bodyweight once a week on Day 1 and 8 of each 21-daytreatment cycles until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Ostatní jména:
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Experimentální: Avelumab + M6223
Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Ostatní jména:
Participants intravenous infusion of M6223 at dose of 1600 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Experimentální: Group D: Avelumab + NKTR-255
Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks in combination with intravenous infusion of NKTR-255 at a dose of 3 micrograms per kilogram (mcg/kg) of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Participants received intravenous infusion of Avelumab at a dose of 800 mg once every 2 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
Ostatní jména:
Participants intravenous infusion of NKTR-255 at a dose of 3 mcg/kg of body weight once every 4 weeks until unacceptable toxicity, withdraw consent or initiation of a new treatment.
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Jiný: JB100 (NCT02603432)
As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432).
Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first.
BSC was administered asper the treating physician.
Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy.
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As per the Clinical Study Protocol, the control group (avelumab alone) was extended by data from an external control, i.e. the JAVELIN Bladder 100 study (JB100) (NCT02603432).
Participants received an intravenous infusion of 10 mg/kg of Avelumab along with best supportive care (BSC), on Day 1 and 15 of each 28 days treatment cycle, until confirmed disease progression, participant refusal, lost to follow up, unacceptable toxicity, or study termination by the sponsor, whichever occurred first.
BSC was administered asper the treating physician.
Participants were followed up until death, end of the study or withdrawal of consent, whichever comes first, regardless of initiation of new anticancer therapy.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions.
The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times.
PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm.
PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
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Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions.
The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times.
PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm.
PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
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Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions.
The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times.
PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm.
PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs)
Časové okno: Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)
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Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment.
Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect.
TEAEs were defined as events with onset date or worsening during the on-treatment period, defined as the time from the first dose of study intervention administration days to the last administration day + 30 days, or the start day of subsequent anticancer therapy - 1 day, whichever occurred first.
TEAEs included serious AEs and non- serous AEs.
AESIs included Infusion-related reactions (IRRs), Immune-related AEs (irAEs), Thromboembolic events, Cytokine release syndrome, QT interval prolongation.
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Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Overall Survival (OS) - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Overall Survival (OS) - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Časové okno: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator- Avelumab + Sacituzumab Govitecan Versus Avelumab
Časové okno: Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD).
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
|
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + M6223 Versus Avelumab
Časové okno: Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD).
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
|
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab
Časové okno: Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD).
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
|
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + Sacituzumab Govitecan Versus Avelumab
Časové okno: Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
|
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator Avelumab + M6223 Versus Avelumab
Časové okno: Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
|
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + NKTR-255 Versus Avelumab
Časové okno: Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
DoR was defined as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to PD or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from first documented objective response to PD or death due to any cause, assessed up to 32 months and 12 days
|
|
Serum Concentrations of Avelumab in Avelumab Monotherapy
Časové okno: C1D1 and C3D29 (pre-dose and end of infusion); C2D15, C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659, and C54D743 (pre-dose) (each cycle is of 2 weeks)
|
Serum concentrations of Avelumab were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1 and C3D29 (pre-dose and end of infusion); C2D15, C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659, and C54D743 (pre-dose) (each cycle is of 2 weeks)
|
|
Serum Concentrations of Avelumab- Avelumab + Sacituzumab Govitecan (SG)
Časové okno: C1D1 and C2D29 (pre-dose and end of infusion); C1D15, C3D43, C5D85, C7D127, C9D169, C13D253, C17D337, C21D421, C25D505, C29D589, C33D673, and C37D757 (pre-dose) (each cycle is of 4 weeks)
|
Serum concentrations of Avelumab in investigational arm (Avelumab + Sacituzumab Govitecan (SG) were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1 and C2D29 (pre-dose and end of infusion); C1D15, C3D43, C5D85, C7D127, C9D169, C13D253, C17D337, C21D421, C25D505, C29D589, C33D673, and C37D757 (pre-dose) (each cycle is of 4 weeks)
|
|
Serum Concentrations of Avelumab- Avelumab + M6623
Časové okno: C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
|
Serum concentrations of Avelumab in investigational arm (Avelumab + M6623) were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day"
|
C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
|
|
Serum Concentrations of Avelumab- Avelumab + NKTR-255
Časové okno: C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
|
Serum concentrations of Avelumab in investigational arm (Avelumab + NKTR-255) were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
|
|
Serum Concentrations of Total Antibody of Sacituzumab Govitecan (SG)
Časové okno: C1D1 and C2D22 (Pre-dose and end of infusion); C1D8, C2D29, C3D43, C5D85, C5D92, C7D127, C7D134, C9D169, C9D176, C13D253, C17D337, C21D421, C21D428, C25D505, C29D589 and C33D673 (Pre-dose) (each cycle is of 4 weeks)
|
Serum concentrations of SG were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1 and C2D22 (Pre-dose and end of infusion); C1D8, C2D29, C3D43, C5D85, C5D92, C7D127, C7D134, C9D169, C9D176, C13D253, C17D337, C21D421, C21D428, C25D505, C29D589 and C33D673 (Pre-dose) (each cycle is of 4 weeks)
|
|
Serum Concentrations of M6223
Časové okno: C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
|
Serum concentrations of M6223 were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1, C2D15 and C3D29 (pre-dose and end of infusion); C1D2, C2D16 (24 hour) C1D8, C2D22 (168 hours); C6D71, C9D113, C12D155, C18D239, C24D323, C30D407, C36D491, C42D575, C48D659 and C54D743 (Pre-dose) (each cycle is of 2 weeks)
|
|
Serum Concentration of NKTR-255
Časové okno: C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
|
Serum concentrations of NKTR-255 were measured.
"C" in the timeframe below refers to "Cycle" and D refers to "Day".
|
C1D1, C2D29, C3D57 and C5D113 (pre-dose and end of infusion); C1D2, C2D30 (24 hour) C1D8, C2D36 (168 hours); C7D169, C10D253, C13D337, C16D421, C19D505, C22D589, C25D673 and C28D757(Pre-dose) (each cycle is of 4 weeks)
|
|
Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab and Combination Drugs
Časové okno: Up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
Number of participants with positive ADA of Avelumab and combination drugs (Sacituzumab Govitecan [SG], M6223 and NKTR-255) were reported.
|
Up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores at Week 13 - Avelumab + SG Versus Avelumab
Časové okno: Baseline, Week 13
|
The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists.
The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep.
Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4).
The overall summary range is 0-36.
The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores.
The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered.
In general, higher scores are better than lower scores.
|
Baseline, Week 13
|
|
Change From Baseline in NCCN FACT FBlSI-18 DRS-P Scores at Week 13 - Avelumab + M6223 Versus Avelumab
Časové okno: Baseline, Week 13
|
The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists.
The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep.
Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4).
The overall summary range is 0-36.
The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores.
The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered.
In general, higher scores are better than lower scores.
|
Baseline, Week 13
|
|
Change From NCCN FACT FBlSI-18 DRS-P Scores at Week 13 -Avelumab + NKTR-255 Versus Avelumab
Časové okno: Baseline, Week 13
|
The NCCN FACT FBlSI-18 is designed to be a stand-alone instrument to measure symptoms and quality of life in participants with urothelial carcinoma and was created using inputs from participants and oncologists.
The disease-related symptoms - physical (DRS-P) subscale uses a subset of physical symptoms which are specific to urothelial carcinoma, i.e., pain, weight loss, urination, weakness, dizziness, meeting family needs, appetite, erection in males, and sleep.
Each question offers 5 answers: not at all (0), a little bit (1), somewhat (2), quite a bit (3), very much (4).
The overall summary range is 0-36.
The scores of negatively stated items (e.g., pain) are reversed and added together with the positively stated scores.
The sum of these item scores are multiplied by the number of items in the subscale, i.e., by 9, and divided by the number of items answered.
In general, higher scores are better than lower scores.
|
Baseline, Week 13
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Vyšetřovatelé
- Ředitel studie: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- Naing A, McKean M, Tolcher A, Victor A, Hu P, Gao W, Nogueira Filho MAF, Kitzing T, Gleicher S, Holland D, Richter E, Tadjalli-Mehr K, Siu LL. TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial. J Immunother Cancer. 2025 Feb 10;13(2):e010584. doi: 10.1136/jitc-2024-010584.
- Hoffman-Censits J, Grivas P, Powles T, Hawley J, Tyroller K, Seeberger S, Guenther S, Jacob N, Mehr KT, Hahn NM. The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. Future Oncol. 2024 Feb;20(4):179-190. doi: 10.2217/fon-2023-0492. Epub 2023 Sep 6.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
17. srpna 2022
Primární dokončení (Aktuální)
20. června 2025
Dokončení studie (Odhadovaný)
22. ledna 2027
Termíny zápisu do studia
První předloženo
5. dubna 2022
První předloženo, které splnilo kritéria kontroly kvality
13. dubna 2022
První zveřejněno (Aktuální)
14. dubna 2022
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
1. září 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
10. srpna 2026
Naposledy ověřeno
1. srpna 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Urogenitální onemocnění
- Urogenitální novotvary
- Novotvary podle místa
- Novotvary
- Mužská urogenitální onemocnění
- Urologická onemocnění
- Ženské urogenitální onemocnění
- Ženské urogenitální onemocnění a těhotenské komplikace
- Novotvary podle histologického typu
- Novotvary, žlázové a epiteliální
- Urologické novotvary
- Karcinom
- Onemocnění močového měchýře
- Novotvary močového měchýře
- Karcinom, přechodná buňka
- Antineoplastická činidla, Imunologická
- Antineoplastická činidla
- Imunologické faktory
- Fyziologické účinky léků
- Imunokonjugáty
- Avelumab
- SACITUZUMAB GOVITECAN
- NKTR-255
Další identifikační čísla studie
- MS100070_0119
- 2023 (Grant/smlouva NIH USA: GRAMMY Museum Foundation)
- 2021-003669-36 (Číslo EudraCT)
- 2023-510139-12-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
Zavázali jsme se zlepšovat veřejné zdraví prostřednictvím odpovědného sdílení údajů z klinických studií.
Po schválení nového přípravku nebo nové indikace pro schválený přípravek v USA i v Evropské unii budou zadavatel studie a/nebo jeho přidružené společnosti sdílet protokoly studie, anonymizovaná data pacientů a údaje na úrovni studie a redigované zprávy o klinických studiích s kvalifikovaní vědečtí a lékařští výzkumníci na požádání, jak je nezbytné pro provádění legitimního výzkumu.
Další informace o tom, jak požádat o data, naleznete na našem webu bit.ly/IPD21
Časový rámec sdílení IPD
Do šesti měsíců po schválení nového přípravku nebo nové indikace pro schválený přípravek ve Spojených státech i v Evropské unii
Kritéria přístupu pro sdílení IPD
Údaje si mohou vyžádat kvalifikovaní vědečtí a lékařští výzkumníci.
Takové žádosti musí být předloženy písemně na portál společnosti a budou interně přezkoumány s ohledem na kritéria kvalifikace výzkumných pracovníků a legitimitu výzkumného návrhu.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ANALYTIC_CODE
- CSR
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ano
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .