Eine Studie zur Sicherheit und Wirksamkeit verschiedener Kombinationen von Avelumab als Therapie bei lokal fortgeschrittenem oder metastasiertem Urothelkarzinom (JAVELIN Bladder Medley)
10. August 2026 aktualisiert von: EMD Serono Research & Development Institute, Inc.
Eine multizentrische, randomisierte, offene Parallelarm-Umbrella-Studie der Phase II zu Avelumab (MSB0010718C) in Kombination mit anderen Antitumormitteln als Erhaltungstherapie bei Teilnehmern mit lokal fortgeschrittenem oder metastasiertem Urothelkarzinom, deren Krankheit mit First Line Platinum nicht fortschritt -Enthaltende Chemotherapie (JAVELIN Bladder Medley)
Der Zweck dieser Studie ist die Bewertung der Sicherheit und Wirksamkeit von Avelumab in Kombination mit anderen Antitumormitteln als Erhaltungstherapie bei Teilnehmern mit Blasenkrebs.
Studienübersicht
Status
Aktiv, nicht rekrutierend
Studientyp
Interventionell
Einschreibung (Tatsächlich)
256
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Bedford Park, Australien
- Flinders Medical Centre
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Footscray, Australien
- Sunshine Hospital - PARENT
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Kurralta Park, Australien
- Ashford Cancer Centre Research
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Liverpool, Australien
- Liverpool Hospital - PARENT
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Newcastle, Australien
- Calvary Mater Newcastle - PARENT
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Southport, Australien
- Tasman Oncology Research Ltd - Oncology
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Sydney, Australien
- Macquarie University Hospital - PARENT
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Westmead, Australien
- The Kinghorn Can Cen
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Antwerp, Belgien
- ZNA Middelheim - Middelheim - account 2
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Brasschaat, Belgien
- AZ Klina - PARENT
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Brussels, Belgien
- Institut Jules Bordet - Medical Oncology
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Ghent, Belgien
- Universitair Ziekenhuis Gent - Medical Oncology
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Kortrijk, Belgien
- AZ Groeninge - Campus Kennedylaan - account 2
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Libramont, Belgien
- Centre Hospitalier de l'Ardenne - PARENT
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Liège, Belgien
- CHU de Liège - PARENT
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Wuerzburg, Belgien
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Essen, Deutschland
- Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
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Frankfurt, Deutschland
- Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
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Halle, Deutschland
- Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
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Mönchengladbach, Deutschland
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Münster, Deutschland
- Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
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Tübingen, Deutschland
- Universitaetsklinikum Tuebingen - Klinik fuer Urologie
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North Rhine-Westphalia
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Muenchen, North Rhine-Westphalia, Deutschland, 41063
- Kliniken Maria Hilf GmbH - Klinik fuer Urologie
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Saxony-Anhalt
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Halle, Saxony-Anhalt, Deutschland, 0044384
- Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
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Angers, Frankreich
- ICO - Site Paul Papin - service d'oncologie medicale
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Bordeaux, Frankreich
- Institut Bergonié - Service d'Oncologie Médicale
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Caen, Frankreich
- Centre François Baclesse - Pathologies Gynecologiques
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Créteil, Frankreich
- Hôpital Henri Mondor - Service d'Oncologie Médicale
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Le Mans, Frankreich
- Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
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Lyon, Frankreich
- Centre Leon Berard - Service d'Oncologie Medicale
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Marseille, Frankreich
- Hôpital de la Timone - service d'urologie
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Nîmes, Frankreich
- Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
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Paris, Frankreich
- Hôpital Cochin - Hematologie et Oncologie Médicale
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Poitiers, Frankreich
- CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
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Rennes, Frankreich
- CRLCC Eugene Marquis - Service d'Oncologie médicale
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Saint-Herblain, Frankreich
- ICO - Site René Gauducheau - Service d'Oncologie medicale
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Strasbourg, Frankreich
- Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
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Strasbourg, Frankreich
- Clinique Sainte-Anne - Service d'Oncologie Médicale
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Hauts De Seine
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Suresnes, Hauts De Seine, Frankreich, 92151
- Hôpital Foch - Service d'Oncologie Médicale
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Athens, Griechenland
- General Hospital of Athens "Alexandra"
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Athens, Griechenland
- University General Hospital "Attikon"
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Athens, Griechenland
- Athens Medical Center
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Thessaloniki, Griechenland
- Euromedica General Clinic of Thessaloniki
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Bologna, Italien
- Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
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Florence, Italien
- Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
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Forlì, Italien
- IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
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Milan, Italien
- Ospedale San Raffaele - U.O. di Oncologia Medica
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Milan, Italien
- Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
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Misterbianco, Italien
- Humanitas Istituto Clinico Catanese - Oncologia Medica
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Naples, Italien
- Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
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Naples, Italien
- Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
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Padova, Italien
- IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
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Pisa, Italien
- Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
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Ravenna, Italien
- Ospedale Santa Maria Delle Croci
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Rome, Italien
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
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San Giovanni Rotondo, Italien
- IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
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Terni, Italien
- Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
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Brampton, Kanada
- William Osler Health System - Brampton Civic Hospital
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Greenfield Park, Kanada
- CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
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Montreal, Kanada
- CHUM Centre de Recherche
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Ottawa, Kanada
- The Ottawa Hospital Cancer Centre
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Badajoz, Spanien
- Hospital Infanta Cristina - Unidad de Fase I
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Barcelona, Spanien
- Hospital del Mar - Servicio de Oncologia
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Barcelona, Spanien
- Hospital de la Santa Creu i Sant Pau - Dept of Oncology
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Barcelona, Spanien
- Hospital Clinic de Barcelona - Servicio de Oncologia
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Barcelona, Spanien
- Hospital Universitario Virgen del Rocio - Oncology Service
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Córdoba, Spanien
- Hospital Universitario Reina Sofia - Dept of Oncology
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Elche, Spanien
- Hospital General Universitario de Elche - Servicio de Oncologia
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Lugo, Spanien
- Hospital Universitario Lucus Augusti - Oncology
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Madrid, Spanien
- Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
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Manresa, Spanien
- ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
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Daejeon, Südkorea
- Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
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Gyeonggi-do, Südkorea
- National Cancer Center
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Seongnam-si, Südkorea
- Seoul National University Bundang Hospital
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Seoul, Südkorea
- Asan Medical Center
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Seoul, Südkorea
- Samsung Medical Center
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Seoul, Südkorea
- Seoul National University Hospital
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Seoul, Südkorea
- Severance Hospital, Yonsei University Health System
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Seoul, Südkorea
- The Catholic University of Korea, Seoul St. Mary's Hospital
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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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Idaho
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Coeur d'Alene, Idaho, Vereinigte Staaten, 83814
- Beacon Cancer Care
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Kansas
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Kansas City, Kansas, Vereinigte Staaten, 66205
- University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
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Maryland
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Baltimore, Maryland, Vereinigte Staaten, 21287
- The Johns Hopkins Hospital
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Baltimore, Maryland, Vereinigte Staaten, 21287-7049
- Johns Hopkins University
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Missouri
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Kansas City, Missouri, Vereinigte Staaten, 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, Vereinigte Staaten, 98109
- Seattle Cancer Care Alliance
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Tacoma, Washington, Vereinigte Staaten, 98405
- Multicare Health System Tacoma General Hospital
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Wisconsin
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Madison, Wisconsin, Vereinigte Staaten, 53706
- University of Wisconsin Cancer Center
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Manchester, Vereinigtes Königreich
- The Christie Hospital - Dept of Oncology
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Preston, Vereinigtes Königreich
- Royal Preston Hospital - Rosemere Cancer Centre
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Greater London
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London, Greater London, Vereinigtes Königreich, 0024514
- Barts Hospital - Dept of Medical Oncology
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Beschreibung
Einschlusskriterien:
- Teilnehmer mit histologisch bestätigtem, inoperablem, lokal fortgeschrittenem oder metastasiertem Urothelkarzinom. Sowohl Übergangszell- als auch gemischte Übergangszell-/Nicht-Übergangszell-Histologien sind zulässig, aber das Übergangszellkarzinom muss die vorherrschende Histologie sein
- Die Teilnehmer haben zu Beginn der Erstlinien-Chemotherapie Stadium IIIA/IIIB mit N1-N3- oder Stadium IV-Erkrankung (gemäß American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis System, 8. Ausgabe) dokumentiert.
- Die letzte Dosis der Erstlinien-Chemotherapie muss mindestens 4 Wochen und nicht mehr als 10 Wochen vor der Randomisierung in der vorliegenden Studie erhalten worden sein
- Geschätzte Lebenserwartung von mindestens 3 Monaten
- Teilnehmer ohne fortschreitende Erkrankung gemäß den RECIST v1.1-Richtlinien nach Abschluss von 4 bis 6 Zyklen einer 1-Liter-Chemotherapie. Die Eignung auf der Grundlage dieses Kriteriums wird durch die Überprüfung der radiologischen Beurteilungen (CT/MRT-Scans) vor und nach der Chemotherapie durch den Prüfarzt bestimmt.
- Leistungsstatus (PS) der Eastern Cooperative Oncology Group (ECOG) 0 oder 1
- Angemessene hämatologische, hepatische und renale Funktion wie im Protokoll definiert
- Andere im Protokoll definierte Einschlusskriterien könnten gelten
Ausschlusskriterien:
- Teilnehmer mit vorheriger Immuntherapie mit Interleukin-2 (IL-2), IL-15, Interferon alfa (IFN-α) oder einem Anti-Programmierter-Todes-Rezeptor-1 (PD-1), Anti-Programmierter-Todes-Ligand 1 (PD-L1 ), Anti-PD-L2-, Anti-CD137- oder zytotoxische T-Zell-Lymphozyten-4 (CTLA-4)-Antikörper (einschließlich Ipilimumab), Anti-TROP2, alle anderen Antikörper oder Medikamente, die speziell auf T-Zell-Kostimulation oder Immun-Checkpoint-Signalwege abzielen, oder eines der Prüfpräparate, die in Kombination mit Avelumab verwendet werden.
- Teilnehmer mit aktiver Infektion 48 Stunden vor der Randomisierung, die eine systemische Therapie erfordert
- Teilnehmer mit bekannter früherer oder vermuteter Überempfindlichkeit gegen Studienmedikamente oder Komponenten in ihren Formulierungen
- Teilnehmer mit vorheriger adjuvanter oder neoadjuvanter systemischer Therapie innerhalb von 12 Monaten nach Randomisierung
- Teilnehmer mit einer Impfung innerhalb von 4 Wochen nach der ersten Dosis der Studienbehandlung und während der Studie ist verboten, mit Ausnahme der Verabreichung von inaktivierten Impfstoffen (z. B. inaktivierten Influenza-Impfstoffen) und replikationsdefizienten Coronavirus-Impfstoffen, die von den örtlichen Gesundheitsbehörden genehmigt oder genehmigt wurden
- Andere im Protokoll definierte Ausschlusskriterien könnten gelten
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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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.
Andere Namen:
|
|
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.
|
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.
Andere Namen:
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.
Andere Namen:
|
|
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.
|
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.
Andere Namen:
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.
|
|
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.
|
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.
Andere Namen:
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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Sonstiges: 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.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
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])
Zeitfenster: 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 + M6223 Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Zeitfenster: 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])
Zeitfenster: 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)
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs)
Zeitfenster: Up to 32 months and 12 days (Current study) and 61 months and 11 days (JB100 extended control group)
|
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)
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Overall Survival (OS) -Avelumab + Sacituzumab Govitecan Versus Avelumab Monotherapy (Avelumab [Control Group] + JB 100 [External Control])
Zeitfenster: 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])
Zeitfenster: 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])
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Ermittler
- Studienleiter: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Allgemeine Veröffentlichungen
- 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.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
17. August 2022
Primärer Abschluss (Tatsächlich)
20. Juni 2025
Studienabschluss (Geschätzt)
22. Januar 2027
Studienanmeldedaten
Zuerst eingereicht
5. April 2022
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
13. April 2022
Zuerst gepostet (Tatsächlich)
14. April 2022
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
1. September 2026
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
10. August 2026
Zuletzt verifiziert
1. August 2026
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Urogenitale Neoplasmen
- Neubildungen nach Standort
- Neubildungen
- Männliche Urogenitalerkrankungen
- Urologische Erkrankungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Neubildungen nach histologischem Typ
- Neubildungen, Drüsen und Epithelien
- Urologische Neubildungen
- Karzinom
- Erkrankungen der Harnblase
- Neoplasien der Harnblase
- Karzinom, Übergangszelle
- Antineoplastische Mittel, immunologische
- Antineoplastische Wirkstoffe
- Immunologische Faktoren
- Physiologische Wirkungen von Arzneimitteln
- Immunkonjugate
- Avelumab
- Sacituzumab Govitecan
- NKTR-255
Andere Studien-ID-Nummern
- MS100070_0119
- 2023 (US NIH Stipendium/Vertrag: GRAMMY Museum Foundation)
- 2021-003669-36 (EudraCT-Nummer)
- 2023-510139-12-00 (Ctis)
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JA
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Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Ja
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .