Исследование безопасности и эффективности различных комбинаций авелумаба в качестве терапии местнораспространенной или метастатической уротелиальной карциномы (JAVELIN Bladder Medley)
10 августа 2026 г. обновлено: EMD Serono Research & Development Institute, Inc.
Фаза II, многоцентровое, рандомизированное, открытое, параллельное, комплексное исследование авелумаба (MSB0010718C) в комбинации с другими противоопухолевыми агентами в качестве поддерживающей терапии у участников с местнораспространенной или метастатической уротелиальной карциномой, у которых заболевание не прогрессировало при применении первой линии платины - Содержит химиотерапию (JAVELIN Bladder Medley)
Целью данного исследования является оценка безопасности и эффективности авелумаба в сочетании с другими противоопухолевыми препаратами в качестве поддерживающей терапии у участников с раком мочевого пузыря.
Обзор исследования
Статус
Активный, не рекрутирующий
Тип исследования
Интервенционный
Регистрация (Действительный)
256
Фаза
- Фаза 2
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Bedford Park, Австралия
- Flinders Medical Centre
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Footscray, Австралия
- Sunshine Hospital - PARENT
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Kurralta Park, Австралия
- Ashford Cancer Centre Research
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Liverpool, Австралия
- Liverpool Hospital - PARENT
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Newcastle, Австралия
- Calvary Mater Newcastle - PARENT
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Southport, Австралия
- Tasman Oncology Research Ltd - Oncology
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Sydney, Австралия
- Macquarie University Hospital - PARENT
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Westmead, Австралия
- The Kinghorn Can Cen
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Antwerp, Бельгия
- ZNA Middelheim - Middelheim - account 2
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Brasschaat, Бельгия
- AZ Klina - PARENT
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Brussels, Бельгия
- Institut Jules Bordet - Medical Oncology
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Ghent, Бельгия
- Universitair Ziekenhuis Gent - Medical Oncology
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Kortrijk, Бельгия
- AZ Groeninge - Campus Kennedylaan - account 2
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Libramont, Бельгия
- Centre Hospitalier de l'Ardenne - PARENT
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Liège, Бельгия
- CHU de Liège - PARENT
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Wuerzburg, Бельгия
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Essen, Германия
- Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
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Frankfurt, Германия
- Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
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Halle, Германия
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Mönchengladbach, Германия
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Münster, Германия
- Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
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Tübingen, Германия
- Universitaetsklinikum Tuebingen - Klinik fuer Urologie
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North Rhine-Westphalia
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Muenchen, North Rhine-Westphalia, Германия, 41063
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Saxony-Anhalt
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Halle, Saxony-Anhalt, Германия, 0044384
- Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
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Athens, Греция
- General Hospital of Athens "Alexandra"
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Athens, Греция
- University General Hospital "Attikon"
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Athens, Греция
- Athens Medical Center
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Thessaloniki, Греция
- Euromedica General Clinic of Thessaloniki
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Badajoz, Испания
- Hospital Infanta Cristina - Unidad de Fase I
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Barcelona, Испания
- Hospital del Mar - Servicio de Oncologia
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Barcelona, Испания
- Hospital de la Santa Creu i Sant Pau - Dept of Oncology
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Barcelona, Испания
- Hospital Clinic de Barcelona - Servicio de Oncologia
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Barcelona, Испания
- Hospital Universitario Virgen del Rocio - Oncology Service
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Córdoba, Испания
- Hospital Universitario Reina Sofia - Dept of Oncology
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Elche, Испания
- Hospital General Universitario de Elche - Servicio de Oncologia
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Lugo, Испания
- Hospital Universitario Lucus Augusti - Oncology
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Madrid, Испания
- Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
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Manresa, Испания
- ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
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Bologna, Италия
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
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Florence, Италия
- Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
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Forlì, Италия
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
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Milan, Италия
- Ospedale San Raffaele - U.O. di Oncologia Medica
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Milan, Италия
- Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
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Misterbianco, Италия
- Humanitas Istituto Clinico Catanese - Oncologia Medica
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Naples, Италия
- Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
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Naples, Италия
- Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
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Padova, Италия
- IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
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Pisa, Италия
- Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
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Ravenna, Италия
- Ospedale Santa Maria Delle Croci
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Rome, Италия
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
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San Giovanni Rotondo, Италия
- IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
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Terni, Италия
- Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
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Brampton, Канада
- William Osler Health System - Brampton Civic Hospital
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Greenfield Park, Канада
- CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
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Montreal, Канада
- CHUM Centre de Recherche
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Ottawa, Канада
- The Ottawa Hospital Cancer Centre
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Manchester, Соединенное Королевство
- The Christie Hospital - Dept of Oncology
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Preston, Соединенное Королевство
- Royal Preston Hospital - Rosemere Cancer Centre
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Greater London
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London, Greater London, Соединенное Королевство, 0024514
- Barts Hospital - Dept of Medical Oncology
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Idaho
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Coeur d'Alene, Idaho, Соединенные Штаты, 83814
- Beacon Cancer Care
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Kansas
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Kansas City, Kansas, Соединенные Штаты, 66205
- University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
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Maryland
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Baltimore, Maryland, Соединенные Штаты, 21287
- The Johns Hopkins Hospital
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Baltimore, Maryland, Соединенные Штаты, 21287-7049
- Johns Hopkins University
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Missouri
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Kansas City, Missouri, Соединенные Штаты, 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, Соединенные Штаты, 98109
- Seattle Cancer Care Alliance
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Tacoma, Washington, Соединенные Штаты, 98405
- Multicare Health System Tacoma General Hospital
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Wisconsin
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Madison, Wisconsin, Соединенные Штаты, 53706
- University of Wisconsin Cancer Center
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Kaohsiung City, Тайвань
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Kaohsiung City, Тайвань
- Kaohsiung Chang Gung Memorial Hospital
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Taichung, Тайвань
- China Medical University Hospital
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Tainan, Тайвань
- Chi Mei Hospital, Liouying
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Taipei, Тайвань
- National Taiwan University Hospital
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Taipei, Тайвань
- Taipei Veterans General Hospital
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Taoyuan, Тайвань
- Chang Gung Memorial Hospital,Linkou
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Angers, Франция
- ICO - Site Paul Papin - service d'oncologie medicale
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Bordeaux, Франция
- Institut Bergonié - Service d'Oncologie Médicale
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Caen, Франция
- Centre François Baclesse - Pathologies Gynecologiques
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Créteil, Франция
- Hôpital Henri Mondor - Service d'Oncologie Médicale
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Le Mans, Франция
- Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
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Lyon, Франция
- Centre Leon Berard - Service d'Oncologie Medicale
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Marseille, Франция
- Hôpital de la Timone - service d'urologie
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Nîmes, Франция
- Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
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Paris, Франция
- Hôpital Cochin - Hematologie et Oncologie Médicale
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Poitiers, Франция
- CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
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Rennes, Франция
- CRLCC Eugene Marquis - Service d'Oncologie médicale
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Saint-Herblain, Франция
- ICO - Site René Gauducheau - Service d'Oncologie medicale
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Strasbourg, Франция
- Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
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Strasbourg, Франция
- Clinique Sainte-Anne - Service d'Oncologie Médicale
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Hauts De Seine
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Suresnes, Hauts De Seine, Франция, 92151
- Hôpital Foch - Service d'Oncologie Médicale
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Daejeon, Южная Корея
- Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
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Gyeonggi-do, Южная Корея
- National Cancer Center
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Seongnam-si, Южная Корея
- Seoul National University Bundang Hospital
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Seoul, Южная Корея
- Asan Medical Center
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Seoul, Южная Корея
- Samsung Medical Center
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Seoul, Южная Корея
- Seoul National University Hospital
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Seoul, Южная Корея
- Severance Hospital, Yonsei University Health System
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Seoul, Южная Корея
- The Catholic University of Korea, Seoul St. Mary's Hospital
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Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
18 лет и старше (Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Нет
Описание
Критерии включения:
- Участники с гистологически подтвержденной нерезектабельной местно-распространенной или метастатической уротелиальной карциномой. Допускаются как переходно-клеточная, так и смешанная переходно-непереходная клеточная гистология, но преобладающей гистологией должна быть переходно-клеточная карцинома.
- Участники задокументировали стадию IIIA/IIIB с N1-N3 или стадию IV заболевания (в соответствии с Американским объединенным комитетом по раку/Международным союзом по системе метастазирования опухолевых узлов, 8-е издание) в начале химиотерапии первой линии.
- Последняя доза химиотерапии первой линии должна быть получена не менее чем за 4 недели и не более чем за 10 недель до рандомизации в настоящем исследовании.
- Предполагаемая продолжительность жизни не менее 3 месяцев
- Участники без прогрессирующего заболевания в соответствии с рекомендациями RECIST v1.1 после завершения от 4 до 6 циклов химиотерапии 1 л. Приемлемость на основе этого критерия будет определяться исследователем при проверке радиологических оценок до химиотерапии и после химиотерапии (КТ/МРТ).
- Статус эффективности Восточной кооперативной онкологической группы (ECOG) (PS) 0 или 1
- Адекватная гематологическая, печеночная и почечная функция, как определено в протоколе
- Могут применяться другие критерии включения, определенные протоколом.
Критерий исключения:
- Участники с предшествующей иммунотерапией интерлейкином-2 (ИЛ-2), ИЛ-15, альфа-интерфероном (ИФН-α) или анти-рецептором запрограммированной смерти-1 (PD-1), анти-лигандом запрограммированной смерти 1 (PD-L1). ), анти-PD-L2, анти-CD137 или антитело к цитотоксическому Т-лимфоциту-4 (CTLA-4) (включая ипилимумаб), анти-TROP2, любое другое антитело или лекарство, специфически нацеленное на костимуляцию Т-клеток или пути иммунных контрольных точек, или любое из исследуемые препараты, используемые в комбинации с авелумабом.
- Участники с активной инфекцией за 48 часов до рандомизации, требующие системной терапии
- Участники с известной предшествующей или предполагаемой гиперчувствительностью к исследуемым препаратам или любому компоненту в их препаратах.
- Участники с предшествующей адъювантной или неоадъювантной системной терапией в течение 12 месяцев после рандомизации
- Участники с вакцинацией в течение 4 недель после первой дозы исследуемого препарата и во время испытаний запрещены, за исключением введения инактивированных вакцин (например, инактивированных вакцин против гриппа) и вакцин против коронавируса с дефицитом репликации, одобренных или разрешенных местными органами здравоохранения.
- Могут применяться другие критерии исключения, определенные протоколом.
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: 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.
Другие имена:
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Экспериментальный: 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.
Другие имена:
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.
Другие имена:
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Экспериментальный: 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.
Другие имена:
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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Экспериментальный: 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.
Другие имена:
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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Другой: 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.
|
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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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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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])
Временное ограничение: 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])
Временное ограничение: Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions.
The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times.
PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm.
PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
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])
Временное ограничение: Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
PFS:defined as time from date of randomization to first documentation of progressive disease (PD) or death, occurring within 2 scheduled tumor assessments after last evaluable assessment or randomization.
PD:at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline/ appearance of 1/more new lesions.
The propensity score (PS)-based weighted Kaplan-Meier estimated median PFS times.
PS were used as weights to minimize impact of confounding factors on estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with sum of weights adding up to number of participants in randomized control arm.
PFS Efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to first documentation of progressive disease (PD) or death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs)
Временное ограничение: 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.
|
Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Временное ограничение: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Overall Survival (OS) - Avelumab + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Временное ограничение: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Overall Survival (OS) - Avelumab + NKTR-255 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Временное ограничение: Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
OS: time from date of randomization to death.
OS was analyzed by using PS-based weighted product-limit (Kaplan-Meier) estimates.
PS were used as weights to minimize the impact of confounding factors on the estimation of causal treatment effects.
Each participant from randomized study was assigned a weight of 1, while participants from external control received a PS-based weight with the sum of weights adding up to number of participants in randomized control arm.
Pre-chosen baseline covariates with possible impact on OS outcome was used to calculate the preference score, i.e., a prevalence adjusted PS defined as the conditional probability of being a participant of the JB100 study in contrast to being a participant of current study given observed baseline covariates.
OS efficacy analysis was prespecified to use a pooled control population comprising the avelumab control arm and JB100 external control cohort; therefore, results are reported for combined control population.
|
Time from date of randomization to death, assessed up to 32 months and 12 days (current study) and 41 months (JB100 extended control group)
|
|
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator- Avelumab + Sacituzumab Govitecan Versus Avelumab
Временное ограничение: Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
ORR is defined as percentage of participants who achieved either a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST v1.1 from randomization to first observation of progression disease (PD).
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
|
Time from randomization to first observation of progression disease (PD), assessed up to 32 months and 12 days
|
|
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator - Avelumab + M6223 Versus Avelumab
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
|
Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Следователи
- Директор по исследованиям: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
Общие публикации
- 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.
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования (Действительный)
17 августа 2022 г.
Первичное завершение (Действительный)
20 июня 2025 г.
Завершение исследования (Оцененный)
22 января 2027 г.
Даты регистрации исследования
Первый отправленный
5 апреля 2022 г.
Впервые представлено, что соответствует критериям контроля качества
13 апреля 2022 г.
Первый опубликованный (Действительный)
14 апреля 2022 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
1 сентября 2026 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
10 августа 2026 г.
Последняя проверка
1 августа 2026 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Урогенитальные заболевания
- Урогенитальные новообразования
- Новообразования по локализации
- Новообразования
- Мужские мочеполовые заболевания
- Урологические заболевания
- Женские урогенитальные заболевания
- Женские мочеполовые заболевания и осложнения беременности
- Новообразования по гистологическому типу
- Новообразования железистые и эпителиальные
- Урологические новообразования
- Карцинома
- Заболевания мочевого пузыря
- Новообразования мочевого пузыря
- Карцинома, переходная клетка
- Противоопухолевые агенты, иммунологические
- Противоопухолевые агенты
- Иммунологические факторы
- Физиологические эффекты лекарств
- Иммуноконъюгаты
- авелумаб
- Sacituzumab Govitecan
- NKTR-255
Другие идентификационные номера исследования
- MS100070_0119
- 2023 (Грант/контракт NIH США: GRAMMY Museum Foundation)
- 2021-003669-36 (Номер EudraCT)
- 2023-510139-12-00 (Ктис)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
ДА
Описание плана IPD
Мы стремимся укреплять общественное здравоохранение посредством ответственного обмена данными клинических испытаний.
После утверждения нового продукта или нового показания для одобренного продукта как в США, так и в Европейском союзе спонсор исследования и/или его дочерние компании будут предоставлять протоколы исследования, анонимные данные о пациентах и данные об уровне исследования, а также отредактированные отчеты о клинических исследованиях с квалифицированных научных и медицинских исследователей, по запросу, если это необходимо для проведения законных исследований.
Дополнительную информацию о том, как запросить данные, можно найти на нашем веб-сайте bit.ly/IPD21.
Сроки обмена IPD
В течение шести месяцев после утверждения нового продукта или нового показания для одобренного продукта как в США, так и в Европейском союзе.
Критерии совместного доступа к IPD
Квалифицированные научные и медицинские исследователи могут запросить данные.
Такие запросы должны быть представлены в письменном виде на портале компании и будут рассмотрены внутри компании с точки зрения критериев квалификации исследователей и легитимности исследовательского предложения.
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- САП
- АНАЛИТИЧЕСКИЙ_КОД
- КСО
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Да
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
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