A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)

NCT ID: NCT05327530

Last Updated: 2026-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

256 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-17

Study Completion Date

2026-06-25

Brief Summary

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The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.

Detailed Description

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Conditions

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Locally Advanced or Metastatic Urothelial Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A: Avelumab

Group Type EXPERIMENTAL

Avelumab

Intervention Type DRUG

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Group B: Avelumab + Sacituzumab Govitecan

Group Type EXPERIMENTAL

Avelumab

Intervention Type DRUG

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Sacituzumab Govitecan

Intervention Type DRUG

Participants will receive sacituzumab govitecan intravenous infusion at dose of 10 milligrams per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles, in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Group C: Avelumab + M6223

Group Type EXPERIMENTAL

Avelumab

Intervention Type DRUG

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

M6223

Intervention Type DRUG

Participants will receive M6223 (anti-T cell-immuno-receptor with Ig and ITM domains \[anti-TIGIT\]) intravenous infusion at dose of 1600 mg Q2W in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Group D: Avelumab + NKTR-255

Group Type EXPERIMENTAL

Avelumab

Intervention Type DRUG

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

NKTR-255

Intervention Type DRUG

Participants will receive NKTR-255 intravenous infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Interventions

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Avelumab

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Intervention Type DRUG

Sacituzumab Govitecan

Participants will receive sacituzumab govitecan intravenous infusion at dose of 10 milligrams per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles, in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Intervention Type DRUG

M6223

Participants will receive M6223 (anti-T cell-immuno-receptor with Ig and ITM domains \[anti-TIGIT\]) intravenous infusion at dose of 1600 mg Q2W in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Intervention Type DRUG

NKTR-255

Participants will receive NKTR-255 intravenous infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Intervention Type DRUG

Other Intervention Names

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MSB0010718C IMMU-132 Trodelvy™ GS-0132

Eligibility Criteria

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Inclusion Criteria

* Participants with histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology
* Participants has documented Stage IIIA/IIIB with N1-N3, or Stage IV disease (per American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis system, 8th edition) at the start of first line chemotherapy.
* The last dose of first line chemotherapy must have been received no less than 4 weeks, and no more than 10 weeks, prior to randomization in the present study
* Estimated life expectancy of at least 3 months
* Participants without progressive disease as per RECIST v1.1 guidelines following completion of 4 to 6 cycles of 1L chemotherapy. Eligibility based on this criterion will be determined by Investigator review of pre chemotherapy and post chemotherapy radiological assessments (CT/MRI scans).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Adequate hematological, hepatic, and renal function as defined in the protocol

Exclusion Criteria

* Participants with prior immunotherapy with Interleukin-2 (IL-2), IL-15, interferon alfa (IFN-α), or an anti programmed death receptor-1 (PD-1), anti programmed death-ligand 1 (PD-L1), anti PD-L2, anti CD137, or cytotoxic T cell lymphocyte-4 (CTLA-4) antibody (including ipilimumab), anti TROP2, anti-T-cell-immuno-receptor with Ig and ITM domains (anti-TIGIT) any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways, agents targeting Nectin-4, or any of the investigational drugs used in combination with avelumab.
* Participants with active infection 48 hours before randomization requiring systemic therapy
* Participants with known prior or suspected hypersensitivity to study drugs or any component in their formulations
* Participants with prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization
* Participants with vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines) administered \>= 2 weeks prior first dose of study treatment. All severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines approved or authorized by local Health Authorities are allowed
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics

UNKNOWN

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

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Beacon Cancer Care

Coeur d'Alene, Idaho, United States

Site Status

University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)

Kansas City, Kansas, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center

Kansas City, Missouri, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Multicare Health System Tacoma General Hospital

Tacoma, Washington, United States

Site Status

University of Wisconsin Cancer Center

Madison, Wisconsin, United States

Site Status

Flinders Medical Centre

Bedford Park, , Australia

Site Status

Sunshine Hospital - PARENT

Footscray, , Australia

Site Status

Ashford Cancer Centre Research

Kurralta Park, , Australia

Site Status

Liverpool Hospital - PARENT

Liverpool, , Australia

Site Status

Calvary Mater Newcastle - PARENT

Newcastle, , Australia

Site Status

Tasman Oncology Research Ltd - Oncology

Southport, , Australia

Site Status

Macquarie University Hospital - PARENT

Sydney, , Australia

Site Status

The Kinghorn Can Cen

Westmead, , Australia

Site Status

ZNA Middelheim - Middelheim - account 2

Antwerp, , Belgium

Site Status

AZ Klina - PARENT

Brasschaat, , Belgium

Site Status

Institut Jules Bordet - Medical Oncology

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Gent - Medical Oncology

Ghent, , Belgium

Site Status

AZ Groeninge - Campus Kennedylaan - account 2

Kortrijk, , Belgium

Site Status

Centre Hospitalier de l'Ardenne - PARENT

Libramont, , Belgium

Site Status

CHU de Liège - PARENT

Liège, , Belgium

Site Status

Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie

Wuerzburg, , Belgium

Site Status

William Osler Health System - Brampton Civic Hospital

Brampton, , Canada

Site Status

CISSS de la Monteregie-Centre - Hospital Charles Le Moyne

Greenfield Park, , Canada

Site Status

CHUM Centre de Recherche

Montreal, , Canada

Site Status

The Ottawa Hospital Cancer Centre

Ottawa, , Canada

Site Status

Hôpital Foch - Service d'Oncologie Médicale

Suresnes, Hauts De Seine, France

Site Status

ICO - Site Paul Papin - service d'oncologie medicale

Angers, , France

Site Status

Institut Bergonié - Service d'Oncologie Médicale

Bordeaux, , France

Site Status

Centre François Baclesse - Pathologies Gynecologiques

Caen, , France

Site Status

Hôpital Henri Mondor - Service d'Oncologie Médicale

Créteil, , France

Site Status

Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical

Le Mans, , France

Site Status

Centre Leon Berard - Service d'Oncologie Medicale

Lyon, , France

Site Status

Hôpital de la Timone - service d'urologie

Marseille, , France

Site Status

Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale

Nîmes, , France

Site Status

Hôpital Cochin - Hematologie et Oncologie Médicale

Paris, , France

Site Status

CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale

Poitiers, , France

Site Status

CRLCC Eugene Marquis - Service d'Oncologie médicale

Rennes, , France

Site Status

ICO - Site René Gauducheau - Service d'Oncologie medicale

Saint-Herblain, , France

Site Status

Clinique Sainte-Anne - Service d'Oncologie Médicale

Strasbourg, , France

Site Status

Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale

Strasbourg, , France

Site Status

Kliniken Maria Hilf GmbH - Klinik fuer Urologie

Muenchen, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie

Halle, Saxony-Anhalt, Germany

Site Status

Universitaetsklinikum Essen - Westdeutsches Tumorzentrum

Essen, , Germany

Site Status

Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2

Frankfurt, , Germany

Site Status

Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie

Halle, , Germany

Site Status

Kliniken Maria Hilf GmbH - Klinik fuer Urologie

Mönchengladbach, , Germany

Site Status

Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie

Münster, , Germany

Site Status

Universitaetsklinikum Tuebingen - Klinik fuer Urologie

Tübingen, , Germany

Site Status

Athens Medical Center

Athens, , Greece

Site Status

General Hospital of Athens "Alexandra"

Athens, , Greece

Site Status

University General Hospital "Attikon"

Athens, , Greece

Site Status

Euromedica General Clinic of Thessaloniki

Thessaloniki, , Greece

Site Status

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica

Bologna, , Italy

Site Status

Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica

Florence, , Italy

Site Status

IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia

Forlì, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria

Milan, , Italy

Site Status

Ospedale San Raffaele - U.O. di Oncologia Medica

Milan, , Italy

Site Status

Humanitas Istituto Clinico Catanese - Oncologia Medica

Misterbianco, , Italy

Site Status

Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A

Napoli, , Italy

Site Status

Istituto Nazionale Tumori Regina Elena IRCCS - Urologia

Napoli, , Italy

Site Status

IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1

Padua, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia

Pisa, , Italy

Site Status

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Rome, , Italy

Site Status

IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica

San Giovanni Rotondo, , Italy

Site Status

Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica

Terni, , Italy

Site Status

Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)

Daejeon, , South Korea

Site Status

National Cancer Center

Gyeonggi-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Infanta Cristina - Unidad de Fase I

Badajoz, , Spain

Site Status

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau - Dept of Oncology

Barcelona, , Spain

Site Status

Hospital del Mar - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Universitario Virgen del Rocio - Oncology Service

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofia - Dept of Oncology

Córdoba, , Spain

Site Status

Hospital General Universitario de Elche - Servicio de Oncologia

Elche, , Spain

Site Status

Hospital Universitario Lucus Augusti - Oncology

Lugo, , Spain

Site Status

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, , Spain

Site Status

ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept

Manresa, , Spain

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Chi Mei Hospital, Liouying

Tainan, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital,Linkou

Taoyuan District, , Taiwan

Site Status

Barts Hospital - Dept of Medical Oncology

London, Greater London, United Kingdom

Site Status

The Christie Hospital - Dept of Oncology

Manchester, , United Kingdom

Site Status

Royal Preston Hospital - Rosemere Cancer Centre

Preston, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Greece Italy South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39929671 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37671748 (View on PubMed)

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2021-003669-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-510139-12-00

Identifier Type: CTIS

Identifier Source: secondary_id

MS100070_0119

Identifier Type: -

Identifier Source: org_study_id

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