A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)
A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)
3 other identifiers
interventional
256
12 countries
97
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2022
Typical duration for phase_2
97 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 5, 2022
CompletedFirst Posted
Study publicly available on registry
April 14, 2022
CompletedStudy Start
First participant enrolled
August 17, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 20, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 25, 2026
ExpectedApril 24, 2026
April 1, 2026
2.8 years
April 5, 2022
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events, and AEs of Special Interest (AESIs) as per Qualitative Toxicity Scale [National Cancer Institute-Common Terminology Criteria for Adverse Events 5.0]
From Randomization up to the last safety follow-up visit at approximately up to 51 months
Secondary Outcomes (6)
Overall Survival (OS)
Time from randomization of study drug until death, assessed approximately up to 51 months
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
Time from randomization of study drug up to 51 months
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months
Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255
Pre-dose up to safety follow up, assessed approximately up to maximum 51 months
Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255
Baseline up to 51 months
- +1 more secondary outcomes
Study Arms (4)
Group A: Avelumab
EXPERIMENTALGroup B: Avelumab + Sacituzumab Govitecan
EXPERIMENTALGroup C: Avelumab + M6223
EXPERIMENTALGroup D: Avelumab + NKTR-255
EXPERIMENTALInterventions
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (97)
Beacon Cancer Care
Coeur d'Alene, Idaho, 83814, United States
University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
Kansas City, Kansas, 66205, United States
Johns Hopkins University
Baltimore, Maryland, 21287-7049, United States
The Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center
Kansas City, Missouri, 66204, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Multicare Health System Tacoma General Hospital
Tacoma, Washington, 98405, United States
University of Wisconsin Cancer Center
Madison, Wisconsin, 53706, United States
Flinders Medical Centre
Bedford Park, Australia
Sunshine Hospital - PARENT
Footscray, Australia
Ashford Cancer Centre Research
Kurralta Park, Australia
Liverpool Hospital - PARENT
Liverpool, Australia
Calvary Mater Newcastle - PARENT
Newcastle, Australia
Tasman Oncology Research Ltd - Oncology
Southport, Australia
Macquarie University Hospital - PARENT
Sydney, Australia
The Kinghorn Can Cen
Westmead, Australia
ZNA Middelheim - Middelheim - account 2
Antwerp, Belgium
AZ Klina - PARENT
Brasschaat, Belgium
Institut Jules Bordet - Medical Oncology
Brussels, Belgium
Universitair Ziekenhuis Gent - Medical Oncology
Ghent, Belgium
AZ Groeninge - Campus Kennedylaan - account 2
Kortrijk, Belgium
Centre Hospitalier de l'Ardenne - PARENT
Libramont, Belgium
CHU de Liège - PARENT
Liège, Belgium
Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
Wuerzburg, Belgium
William Osler Health System - Brampton Civic Hospital
Brampton, Canada
CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
Greenfield Park, Canada
CHUM Centre de Recherche
Montreal, Canada
The Ottawa Hospital Cancer Centre
Ottawa, Canada
Hôpital Foch - Service d'Oncologie Médicale
Suresnes, Hauts De Seine, 92151, France
ICO - Site Paul Papin - service d'oncologie medicale
Angers, France
Institut Bergonié - Service d'Oncologie Médicale
Bordeaux, France
Centre François Baclesse - Pathologies Gynecologiques
Caen, France
Hôpital Henri Mondor - Service d'Oncologie Médicale
Créteil, France
Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
Le Mans, France
Centre Leon Berard - Service d'Oncologie Medicale
Lyon, France
Hôpital de la Timone - service d'urologie
Marseille, France
Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
Nîmes, France
Hôpital Cochin - Hematologie et Oncologie Médicale
Paris, France
CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
Poitiers, France
CRLCC Eugene Marquis - Service d'Oncologie médicale
Rennes, France
ICO - Site René Gauducheau - Service d'Oncologie medicale
Saint-Herblain, France
Clinique Sainte-Anne - Service d'Oncologie Médicale
Strasbourg, France
Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
Strasbourg, France
Kliniken Maria Hilf GmbH - Klinik fuer Urologie
Muenchen, North Rhine-Westphalia, 41063, Germany
Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
Halle, Saxony-Anhalt, 0044384, Germany
Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
Essen, Germany
Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
Frankfurt, Germany
Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
Halle, Germany
Kliniken Maria Hilf GmbH - Klinik fuer Urologie
Mönchengladbach, Germany
Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
Münster, Germany
Universitaetsklinikum Tuebingen - Klinik fuer Urologie
Tübingen, Germany
Athens Medical Center
Athens, Greece
General Hospital of Athens "Alexandra"
Athens, Greece
University General Hospital "Attikon"
Athens, Greece
Euromedica General Clinic of Thessaloniki
Thessaloniki, Greece
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
Bologna, Italy
Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
Florence, Italy
IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
Forlì, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
Milan, Italy
Ospedale San Raffaele - U.O. di Oncologia Medica
Milan, Italy
Humanitas Istituto Clinico Catanese - Oncologia Medica
Misterbianco, Italy
Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
Naples, Italy
Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
Naples, Italy
IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
Padova, Italy
Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
Pisa, Italy
Ospedale Santa Maria delle Croci
Ravenna, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
Rome, Italy
IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
San Giovanni Rotondo, Italy
Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
Terni, Italy
Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
Daejeon, South Korea
National Cancer Center
Gyeonggi-do, South Korea
Seoul National University Bundang Hospital
Seongnam-si, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University Hospital
Seoul, South Korea
Severance Hospital, Yonsei University Health System
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, South Korea
Hospital Infanta Cristina - Unidad de Fase I
Badajoz, Spain
Hospital Clinic de Barcelona - Servicio de Oncologia
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau - Dept of Oncology
Barcelona, Spain
Hospital del Mar - Servicio de Oncologia
Barcelona, Spain
Hospital Universitario Virgen del Rocio - Oncology Service
Barcelona, Spain
Hospital Universitario Reina Sofia - Dept of Oncology
Córdoba, Spain
Hospital General Universitario de Elche - Servicio de Oncologia
Elche, Spain
Hospital Universitario Lucus Augusti - Oncology
Lugo, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
Madrid, Spain
ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
Manresa, Spain
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
China Medical University Hospital
Taichung, Taiwan
Chi Mei Hospital, Liouying
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Chang Gung Memorial Hospital,Linkou
Taoyuan District, Taiwan
Barts Hospital - Dept of Medical Oncology
London, Greater London, 0024514, United Kingdom
The Christie Hospital - Dept of Oncology
Manchester, United Kingdom
Royal Preston Hospital - Rosemere Cancer Centre
Preston, United Kingdom
Related Publications (2)
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.
PMID: 39929671DERIVEDHoffman-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.
PMID: 37671748DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2022
First Posted
April 14, 2022
Study Start
August 17, 2022
Primary Completion
June 20, 2025
Study Completion (Estimated)
June 25, 2026
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
- Time Frame
- Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
- Access Criteria
- Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21