Un estudio de la seguridad y eficacia de varias combinaciones de avelumab como terapia en el carcinoma urotelial metastásico o localmente avanzado (JAVELIN Bladder Medley)
10 de agosto de 2026 actualizado por: EMD Serono Research & Development Institute, Inc.
Estudio de fase II, multicéntrico, aleatorizado, abierto, paralelo, de avelumab (MSB0010718C) en combinación con otros agentes antitumorales como tratamiento de mantenimiento en participantes con carcinoma urotelial metastásico o localmente avanzado cuya enfermedad no progresó con platino de primera línea -Quimioterapia que contiene (JAVELIN Vejiga Medley)
El propósito de este estudio es evaluar la seguridad y eficacia de avelumab en combinación con otros agentes antitumorales como tratamiento de mantenimiento en pacientes con cáncer de vejiga.
Descripción general del estudio
Estado
Activo, no reclutando
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
256
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Essen, Alemania
- Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
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Frankfurt, Alemania
- Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
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Halle, Alemania
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Mönchengladbach, Alemania
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Münster, Alemania
- Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
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Tübingen, Alemania
- Universitaetsklinikum Tuebingen - Klinik fuer Urologie
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North Rhine-Westphalia
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Muenchen, North Rhine-Westphalia, Alemania, 41063
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Saxony-Anhalt
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Halle, Saxony-Anhalt, Alemania, 0044384
- Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
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Bedford Park, Australia
- Flinders Medical Centre
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Footscray, Australia
- Sunshine Hospital - PARENT
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Kurralta Park, Australia
- Ashford Cancer Centre Research
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Liverpool, Australia
- Liverpool Hospital - PARENT
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Newcastle, Australia
- Calvary Mater Newcastle - PARENT
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Southport, Australia
- Tasman Oncology Research Ltd - Oncology
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Sydney, Australia
- Macquarie University Hospital - PARENT
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Westmead, Australia
- The Kinghorn Can Cen
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Antwerp, Bélgica
- ZNA Middelheim - Middelheim - account 2
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Brasschaat, Bélgica
- AZ Klina - PARENT
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Brussels, Bélgica
- Institut Jules Bordet - Medical Oncology
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Ghent, Bélgica
- Universitair Ziekenhuis Gent - Medical Oncology
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Kortrijk, Bélgica
- AZ Groeninge - Campus Kennedylaan - account 2
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Libramont, Bélgica
- Centre Hospitalier de l'Ardenne - PARENT
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Liège, Bélgica
- CHU de Liège - PARENT
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Wuerzburg, Bélgica
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Brampton, Canadá
- William Osler Health System - Brampton Civic Hospital
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Greenfield Park, Canadá
- CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
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Montreal, Canadá
- CHUM Centre de Recherche
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Ottawa, Canadá
- The Ottawa Hospital Cancer Centre
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Daejeon, Corea del Sur
- Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
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Gyeonggi-do, Corea del Sur
- National Cancer Center
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Seongnam-si, Corea del Sur
- Seoul National University Bundang Hospital
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Seoul, Corea del Sur
- Asan Medical Center
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Seoul, Corea del Sur
- Samsung Medical Center
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Seoul, Corea del Sur
- Seoul National University Hospital
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Seoul, Corea del Sur
- Severance Hospital, Yonsei University Health System
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Seoul, Corea del Sur
- The Catholic University of Korea, Seoul St. Mary's Hospital
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Badajoz, España
- Hospital Infanta Cristina - Unidad de Fase I
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Barcelona, España
- Hospital del Mar - Servicio de Oncologia
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Barcelona, España
- Hospital de la Santa Creu i Sant Pau - Dept of Oncology
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Barcelona, España
- Hospital Clinic de Barcelona - Servicio de Oncologia
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Barcelona, España
- Hospital Universitario Virgen del Rocio - Oncology Service
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Córdoba, España
- Hospital Universitario Reina Sofia - Dept of Oncology
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Elche, España
- Hospital General Universitario de Elche - Servicio de Oncologia
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Lugo, España
- Hospital Universitario Lucus Augusti - Oncology
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Madrid, España
- Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
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Manresa, España
- ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
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Idaho
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Coeur d'Alene, Idaho, Estados Unidos, 83814
- Beacon Cancer Care
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Kansas
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Kansas City, Kansas, Estados Unidos, 66205
- University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- The Johns Hopkins Hospital
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Baltimore, Maryland, Estados Unidos, 21287-7049
- Johns Hopkins University
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Missouri
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Kansas City, Missouri, Estados Unidos, 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, Estados Unidos, 98109
- Seattle Cancer Care Alliance
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Tacoma, Washington, Estados Unidos, 98405
- Multicare Health System Tacoma General Hospital
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53706
- University of Wisconsin Cancer Center
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Angers, Francia
- ICO - Site Paul Papin - service d'oncologie medicale
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Bordeaux, Francia
- Institut Bergonié - Service d'Oncologie Médicale
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Caen, Francia
- Centre François Baclesse - Pathologies Gynecologiques
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Créteil, Francia
- Hôpital Henri Mondor - Service d'Oncologie Médicale
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Le Mans, Francia
- Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
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Lyon, Francia
- Centre Leon Berard - Service d'Oncologie Medicale
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Marseille, Francia
- Hôpital de la Timone - service d'urologie
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Nîmes, Francia
- Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
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Paris, Francia
- Hôpital Cochin - Hematologie et Oncologie Médicale
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Poitiers, Francia
- CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
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Rennes, Francia
- CRLCC Eugene Marquis - Service d'Oncologie médicale
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Saint-Herblain, Francia
- ICO - Site René Gauducheau - Service d'Oncologie medicale
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Strasbourg, Francia
- Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
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Strasbourg, Francia
- Clinique Sainte-Anne - Service d'Oncologie Médicale
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Hauts De Seine
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Suresnes, Hauts De Seine, Francia, 92151
- Hôpital Foch - Service d'Oncologie Médicale
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Athens, Grecia
- General Hospital of Athens "Alexandra"
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Athens, Grecia
- University General Hospital "Attikon"
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Athens, Grecia
- Athens Medical Center
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Thessaloniki, Grecia
- Euromedica General Clinic of Thessaloniki
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Bologna, Italia
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
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Florence, Italia
- Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
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Forlì, Italia
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
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Milan, Italia
- Ospedale San Raffaele - U.O. di Oncologia Medica
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Milan, Italia
- Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
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Misterbianco, Italia
- Humanitas Istituto Clinico Catanese - Oncologia Medica
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Naples, Italia
- Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
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Naples, Italia
- Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
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Padova, Italia
- IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
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Pisa, Italia
- Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
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Ravenna, Italia
- Ospedale Santa Maria Delle Croci
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Rome, Italia
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
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San Giovanni Rotondo, Italia
- IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
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Terni, Italia
- Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
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Manchester, Reino Unido
- The Christie Hospital - Dept of Oncology
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Preston, Reino Unido
- Royal Preston Hospital - Rosemere Cancer Centre
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Greater London
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London, Greater London, Reino Unido, 0024514
- Barts Hospital - Dept of Medical Oncology
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Kaohsiung City, Taiwán
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Kaohsiung City, Taiwán
- Kaohsiung Chang Gung Memorial Hospital
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Taichung, Taiwán
- China Medical University Hospital
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Tainan, Taiwán
- Chi Mei Hospital, Liouying
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Taipei, Taiwán
- National Taiwan University Hospital
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Taipei, Taiwán
- Taipei Veterans General Hospital
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Taoyuan, Taiwán
- Chang Gung Memorial Hospital,Linkou
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Descripción
Criterios de inclusión:
- Participantes con carcinoma urotelial metastásico o localmente avanzado no resecable confirmado histológicamente. Se permiten tanto las histologías de células transicionales como las mixtas de células transicionales/no transicionales, pero el carcinoma de células transicionales debe ser la histología predominante.
- Los participantes han documentado el estadio IIIA/IIIB con N1-N3, o la enfermedad en estadio IV (según el sistema de metástasis de nódulos tumorales del Comité Conjunto Estadounidense sobre el Cáncer/Unión Internacional para el Control del Cáncer, 8.ª edición) al comienzo de la quimioterapia de primera línea.
- La última dosis de quimioterapia de primera línea debe haberse recibido no menos de 4 semanas y no más de 10 semanas antes de la aleatorización en el presente estudio.
- Esperanza de vida estimada de al menos 3 meses.
- Participantes sin enfermedad progresiva según las pautas RECIST v1.1 después de completar de 4 a 6 ciclos de quimioterapia de 1 litro. La elegibilidad basada en este criterio será determinada por la revisión del investigador de las evaluaciones radiológicas previas a la quimioterapia y posteriores a la quimioterapia (tomografías computarizadas/resonancias magnéticas).
- Estado funcional (PS) del Grupo Oncológico Cooperativo del Este (ECOG) 0 o 1
- Función hematológica, hepática y renal adecuada según lo definido en el protocolo
- Podrían aplicarse otros criterios de inclusión definidos en el protocolo
Criterio de exclusión:
- Participantes con inmunoterapia previa con interleucina-2 (IL-2), IL-15, interferón alfa (IFN-α) o un anti-receptor de muerte programada-1 (PD-1), anti-ligando de muerte programada 1 (PD-L1 ), anti PD-L2, anti CD137 o anticuerpo linfocito-4 de células T citotóxicas (CTLA-4) (incluido ipilimumab), anti TROP2, cualquier otro anticuerpo o fármaco dirigido específicamente a la coestimulación de células T o vías de puntos de control inmunitarios, o cualquiera de los fármacos en investigación utilizados en combinación con avelumab.
- Participantes con infección activa 48 horas antes de la aleatorización que requieren tratamiento sistémico
- Participantes con hipersensibilidad previa conocida o sospechada a los fármacos del estudio o a cualquier componente de sus formulaciones
- Participantes con tratamiento sistémico adyuvante o neoadyuvante previo dentro de los 12 meses posteriores a la aleatorización
- Participantes vacunados dentro de las 4 semanas posteriores a la primera dosis del tratamiento del estudio y durante el ensayo está prohibido, excepto para la administración de vacunas inactivadas (por ejemplo, vacunas inactivadas contra la influenza) y vacunas contra el coronavirus de replicación deficiente aprobadas o autorizadas por las autoridades sanitarias locales.
- Podrían aplicarse otros criterios de exclusión definidos en el protocolo
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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.
Otros nombres:
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Experimental: 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.
Otros nombres:
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.
Otros nombres:
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Experimental: 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.
Otros nombres:
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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Experimental: 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.
Otros nombres:
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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Otro: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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])
Periodo de tiempo: 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])
Periodo de tiempo: 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 + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Periodo de tiempo: 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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Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs)
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Periodo de tiempo: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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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.
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Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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Overall Survival (OS) - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Periodo de tiempo: 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)
|
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Overall Survival (OS) - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Periodo de tiempo: 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.
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Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
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Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator- Avelumab + Sacituzumab Govitecan Versus Avelumab
Periodo de tiempo: Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
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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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de agosto de 2022
Finalización primaria (Actual)
20 de junio de 2025
Finalización del estudio (Estimado)
22 de enero de 2027
Fechas de registro del estudio
Enviado por primera vez
5 de abril de 2022
Primero enviado que cumplió con los criterios de control de calidad
13 de abril de 2022
Publicado por primera vez (Actual)
14 de abril de 2022
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
1 de septiembre de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
10 de agosto de 2026
Última verificación
1 de agosto de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales masculinas
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Neoplasias Urológicas
- Carcinoma
- Enfermedades de la vejiga urinaria
- Neoplasias de la vejiga urinaria
- Carcinoma De Células De Transición
- Agentes antineoplásicos inmunológicos
- Agentes antineoplásicos
- Factores inmunológicos
- Efectos fisiológicos de las drogas
- Inmunoconjugados
- atvelumab
- Sacituzumab Govitecan
- NKTR-255
Otros números de identificación del estudio
- MS100070_0119
- 2023 (Subvención/contrato del NIH de EE. UU.: GRAMMY Museum Foundation)
- 2021-003669-36 (Número EudraCT)
- 2023-510139-12-00 (Ctis)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Estamos comprometidos a mejorar la salud pública mediante el intercambio responsable de datos de ensayos clínicos.
Luego de la aprobación de un nuevo producto o una nueva indicación para un producto aprobado tanto en los EE. UU. como en la Unión Europea, el patrocinador del estudio y/o sus compañías afiliadas compartirán los protocolos del estudio, los datos anónimos del paciente y los datos del nivel del estudio, y los informes del estudio clínico redactados con investigadores científicos y médicos calificados, previa solicitud, según sea necesario para realizar investigaciones legítimas.
Puede encontrar más información sobre cómo solicitar datos en nuestro sitio web bit.ly/IPD21
Marco de tiempo para compartir IPD
Dentro de los seis meses posteriores a la aprobación de un nuevo producto o una nueva indicación para un producto aprobado tanto en los Estados Unidos como en la Unión Europea
Criterios de acceso compartido de IPD
Investigadores científicos y médicos calificados pueden solicitar los datos.
Dichas solicitudes deberán presentarse por escrito al portal de la empresa y serán revisadas internamente en cuanto a los criterios de calificación de los investigadores y la legitimidad de la propuesta de investigación.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CÓDIGO_ANALÍTICO
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .