Um estudo da segurança e eficácia de várias combinações de avelumabe como terapia em carcinoma urotelial localmente avançado ou metastático (JAVELIN Bexiga Medley)
10 de agosto de 2026 atualizado por: EMD Serono Research & Development Institute, Inc.
Um estudo de fase II, multicêntrico, randomizado, aberto, de braço paralelo, guarda-chuva de Avelumab (MSB0010718C) em combinação com outros agentes antitumorais como tratamento de manutenção em participantes com carcinoma urotelial localmente avançado ou metastático cuja doença não progrediu com platina de primeira linha -Contendo Quimioterapia (JAVELIN Bexiga Medley)
O objetivo deste estudo é avaliar a segurança e a eficácia do avelumabe em combinação com outros agentes antitumorais como tratamento de manutenção em participantes com câncer de bexiga.
Visão geral do estudo
Status
Ativo, não recrutando
Tipo de estudo
Intervencional
Inscrição (Real)
256
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Essen, Alemanha
- Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
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Frankfurt, Alemanha
- Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
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Halle, Alemanha
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Mönchengladbach, Alemanha
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Münster, Alemanha
- Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
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Tübingen, Alemanha
- Universitaetsklinikum Tuebingen - Klinik fuer Urologie
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North Rhine-Westphalia
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Muenchen, North Rhine-Westphalia, Alemanha, 41063
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Saxony-Anhalt
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Halle, Saxony-Anhalt, Alemanha, 0044384
- Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
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Bedford Park, Austrália
- Flinders Medical Centre
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Footscray, Austrália
- Sunshine Hospital - PARENT
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Kurralta Park, Austrália
- Ashford Cancer Centre Research
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Liverpool, Austrália
- Liverpool Hospital - PARENT
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Newcastle, Austrália
- Calvary Mater Newcastle - PARENT
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Southport, Austrália
- Tasman Oncology Research Ltd - Oncology
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Sydney, Austrália
- Macquarie University Hospital - PARENT
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Westmead, Austrália
- 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, Coréia do Sul
- Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
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Gyeonggi-do, Coréia do Sul
- National Cancer Center
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Seongnam-si, Coréia do Sul
- Seoul National University Bundang Hospital
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Seoul, Coréia do Sul
- Asan Medical Center
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Seoul, Coréia do Sul
- Samsung Medical Center
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Seoul, Coréia do Sul
- Seoul National University Hospital
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Seoul, Coréia do Sul
- Severance Hospital, Yonsei University Health System
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Seoul, Coréia do Sul
- The Catholic University of Korea, Seoul St. Mary's Hospital
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Badajoz, Espanha
- Hospital Infanta Cristina - Unidad de Fase I
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Barcelona, Espanha
- Hospital del Mar - Servicio de Oncologia
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Barcelona, Espanha
- Hospital de la Santa Creu i Sant Pau - Dept of Oncology
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Barcelona, Espanha
- Hospital Clinic de Barcelona - Servicio de Oncologia
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Barcelona, Espanha
- Hospital Universitario Virgen del Rocio - Oncology Service
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Córdoba, Espanha
- Hospital Universitario Reina Sofia - Dept of Oncology
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Elche, Espanha
- Hospital General Universitario de Elche - Servicio de Oncologia
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Lugo, Espanha
- Hospital Universitario Lucus Augusti - Oncology
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Madrid, Espanha
- Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
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Manresa, Espanha
- 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, França
- ICO - Site Paul Papin - service d'oncologie medicale
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Bordeaux, França
- Institut Bergonié - Service d'Oncologie Médicale
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Caen, França
- Centre François Baclesse - Pathologies Gynecologiques
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Créteil, França
- Hôpital Henri Mondor - Service d'Oncologie Médicale
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Le Mans, França
- Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
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Lyon, França
- Centre Leon Berard - Service d'Oncologie Medicale
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Marseille, França
- Hôpital de la Timone - service d'urologie
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Nîmes, França
- Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
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Paris, França
- Hôpital Cochin - Hematologie et Oncologie Médicale
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Poitiers, França
- CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
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Rennes, França
- CRLCC Eugene Marquis - Service d'Oncologie médicale
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Saint-Herblain, França
- ICO - Site René Gauducheau - Service d'Oncologie medicale
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Strasbourg, França
- Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
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Strasbourg, França
- Clinique Sainte-Anne - Service d'Oncologie Médicale
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Hauts De Seine
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Suresnes, Hauts De Seine, França, 92151
- Hôpital Foch - Service d'Oncologie Médicale
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Athens, Grécia
- General Hospital of Athens "Alexandra"
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Athens, Grécia
- University General Hospital "Attikon"
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Athens, Grécia
- Athens Medical Center
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Thessaloniki, Grécia
- Euromedica General Clinic of Thessaloniki
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Bologna, Itália
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
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Florence, Itália
- Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
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Forlì, Itália
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
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Milan, Itália
- Ospedale San Raffaele - U.O. di Oncologia Medica
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Milan, Itália
- Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
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Misterbianco, Itália
- Humanitas Istituto Clinico Catanese - Oncologia Medica
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Naples, Itália
- Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
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Naples, Itália
- Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
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Padova, Itália
- IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
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Pisa, Itália
- Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
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Ravenna, Itália
- Ospedale Santa Maria Delle Croci
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Rome, Itália
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
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San Giovanni Rotondo, Itália
- IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
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Terni, Itália
- 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, Taiwan
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Kaohsiung City, Taiwan
- Kaohsiung Chang Gung Memorial Hospital
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Taichung, Taiwan
- China Medical University Hospital
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Tainan, Taiwan
- Chi Mei Hospital, Liouying
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Taipei, Taiwan
- National Taiwan University Hospital
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Taipei, Taiwan
- Taipei Veterans General Hospital
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Taoyuan, Taiwan
- Chang Gung Memorial Hospital,Linkou
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Descrição
Critério de inclusão:
- Participantes com carcinoma urotelial metastático ou localmente avançado irressecável confirmado histologicamente. Ambas as histologias de células transicionais e mistas transicionais/não transicionais são permitidas, mas o carcinoma de células transicionais deve ser a histologia predominante
- Os participantes documentaram o Estágio IIIA/IIIB com doença N1-N3 ou Estágio IV (de acordo com o American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis system, 8ª edição) no início da quimioterapia de primeira linha.
- A última dose de quimioterapia de primeira linha deve ter sido recebida não menos que 4 semanas e não mais que 10 semanas antes da randomização no presente estudo
- Expectativa de vida estimada de pelo menos 3 meses
- Participantes sem doença progressiva de acordo com as diretrizes RECIST v1.1 após a conclusão de 4 a 6 ciclos de quimioterapia 1L. A elegibilidade com base neste critério será determinada pela revisão do investigador das avaliações radiológicas pré-quimioterapia e pós-quimioterapia (tomografia computadorizada/ressonância magnética).
- Status de desempenho (PS) do Eastern Cooperative Oncology Group (ECOG) 0 ou 1
- Função hematológica, hepática e renal adequada, conforme definido no protocolo
- Outros critérios de inclusão definidos pelo protocolo podem ser aplicados
Critério de exclusão:
- Participantes com imunoterapia anterior com Interleucina-2 (IL-2), IL-15, interferon alfa (IFN-α) ou um antirreceptor de morte programada-1 (PD-1), antiligante de morte programada 1 (PD-L1 ), anticorpo anti PD-L2, anti CD137 ou linfócito-4 de células T citotóxicas (CTLA-4) (incluindo ipilimumabe), anti TROP2, qualquer outro anticorpo ou medicamento direcionado especificamente à co-estimulação de células T ou vias de ponto de controle imunológico, ou qualquer um dos medicamentos em investigação usados em combinação com avelumabe.
- Participantes com infecção ativa 48 horas antes da randomização que requerem terapia sistêmica
- Participantes com hipersensibilidade prévia ou suspeita conhecida aos medicamentos do estudo ou a qualquer componente de suas formulações
- Participantes com terapia sistêmica adjuvante ou neoadjuvante anterior dentro de 12 meses após a randomização
- Participantes com vacinação dentro de 4 semanas após a primeira dose do tratamento do estudo e durante o estudo são proibidos, exceto para administração de vacinas inativadas (por exemplo, vacinas inativadas contra influenza) e vacinas contra o coronavírus com deficiência de replicação aprovadas ou autorizadas pelas autoridades de saúde locais
- Outros critérios de exclusão definidos pelo protocolo podem ser aplicados
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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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.
Outros nomes:
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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.
Outros nomes:
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.
Outros nomes:
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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.
Outros nomes:
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.
Outros nomes:
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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Outro: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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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])
Prazo: 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])
Prazo: 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])
Prazo: 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.
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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)
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Prazo: 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])
Prazo: 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])
Prazo: 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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Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator- Avelumab + Sacituzumab Govitecan Versus Avelumab
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
17 de agosto de 2022
Conclusão Primária (Real)
20 de junho de 2025
Conclusão do estudo (Estimado)
22 de janeiro de 2027
Datas de inscrição no estudo
Enviado pela primeira vez
5 de abril de 2022
Enviado pela primeira vez que atendeu aos critérios de CQ
13 de abril de 2022
Primeira postagem (Real)
14 de abril de 2022
Atualizações de registro de estudo
Última Atualização Postada (Real)
1 de setembro de 2026
Última atualização enviada que atendeu aos critérios de controle de qualidade
10 de agosto de 2026
Última verificação
1 de agosto de 2026
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Masculinas
- Doenças Urológicas
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Neoplasias por Tipo Histológico
- Neoplasias Glandulares e Epiteliais
- Neoplasias Urológicas
- Carcinoma
- Doenças da Bexiga Urinária
- Neoplasias da Bexiga Urinária
- Carcinoma de Células de Transição
- Agentes Antineoplásicos Imunológicos
- Agentes Antineoplásicos
- Fatores Imunológicos
- Efeitos fisiológicos das drogas
- Imunoconjugados
- Avelumab
- sacituzumab GoviteCan
- NKTR-255
Outros números de identificação do estudo
- MS100070_0119
- 2023 (Concessão/Contrato do NIH dos EUA: GRAMMY Museum Foundation)
- 2021-003669-36 (Número EudraCT)
- 2023-510139-12-00 (Ctis)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
SIM
Descrição do plano IPD
Estamos comprometidos em melhorar a saúde pública por meio do compartilhamento responsável de dados de ensaios clínicos.
Após a aprovação de um novo produto ou uma nova indicação para um produto aprovado nos EUA e na União Europeia, o patrocinador do estudo e/ou suas empresas afiliadas compartilharão protocolos de estudo, dados anônimos de pacientes e dados de nível de estudo e relatórios de estudos clínicos redigidos com pesquisadores científicos e médicos qualificados, mediante solicitação, conforme necessário para a realização de pesquisas legítimas.
Mais informações sobre como solicitar dados podem ser encontradas em nosso site bit.ly/IPD21
Prazo de Compartilhamento de IPD
Dentro de seis meses após a aprovação de um novo produto ou uma nova indicação para um produto aprovado nos Estados Unidos e na União Europeia
Critérios de acesso de compartilhamento IPD
Pesquisadores científicos e médicos qualificados podem solicitar os dados.
Tais solicitações devem ser encaminhadas por escrito ao portal da empresa e serão analisadas internamente quanto aos critérios de qualificação dos pesquisadores e legitimidade da proposta de pesquisa.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
- ANALYTIC_CODE
- CSR
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .