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

Phase 2

Active, not recruiting

• Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
• Interventions: Drug: Avelumab; Drug: NKTR-255; Drug: Sacituzumab Govitecan; Drug: M6223

• Registration Number: NCT05327530
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-04-13
• Study First Posted: 2022-04-14
• Study Start: 2022-08-17
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-04
• Primary Completion: 2025-01-23
• Study Completion: 2025-01-23

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 256

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
• Other protocol defined inclusion criteria could apply

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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
• Other protocol defined exclusion criteria could apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group D: Avelumab + NKTR-255	NKTR-255	-
Group B: Avelumab + Sacituzumab Govitecan	Sacituzumab Govitecan	-
Group C: Avelumab + M6223	M6223	-
Group A: Avelumab	Avelumab	-
Group B: Avelumab + Sacituzumab Govitecan	Avelumab	-
Group C: Avelumab + M6223	Avelumab	-
Group D: Avelumab + NKTR-255	Avelumab	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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	Baseline, Week 13

Trial Locations

Locations (96)

Beacon Cancer Care; 🇺🇸 Coeur d'Alene, Idaho, United States

University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN); 🇺🇸 Kansas City, Kansas, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

The Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center; 🇺🇸 Kansas City, Missouri, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Multicare Health System Tacoma General Hospital; 🇺🇸 Tacoma, Washington, United States

University of Wisconsin Cancer Center; 🇺🇸 Madison, Wisconsin, United States

Flinders Medical Centre; 🇦🇺 Bedford Park, Australia

Monash Medical Centre Clayton; 🇦🇺 Clayton, 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; 🇧🇪 Antwerpen, Belgium

AZ Klina - PARENT; 🇧🇪 Brasschaat, Belgium

Institut Jules Bordet - Medical Oncology; 🇧🇪 Bruxelles, Belgium

Universitair Ziekenhuis Gent - Medical Oncology; 🇧🇪 Gent, Belgium

AZ Groeninge - Campus Kennedylaan - account 2; 🇧🇪 Kortrijk, Belgium

Centre Hospitalier de l'Ardenne - PARENT; 🇧🇪 Libramont, Belgium

CHU de Liège - PARENT; 🇧🇪 Liege, Belgium

Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie; 🇩🇪 Halle, Germany

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 Cedex, Hauts De Seine, France

ICO - Site Paul Papin - service d'oncologie medicale; 🇫🇷 Angers cedex 2, France

Institut Bergonié - Service d'Oncologie Médicale; 🇫🇷 Bordeaux Cedex, France

Centre François Baclesse - Pathologies Gynecologiques; 🇫🇷 Caen CEDEX, France

Hôpital Henri Mondor - Service d'Oncologie Médicale; 🇫🇷 Creteil, 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 Cedex 5, 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 Cedex, France

CRLCC Eugene Marquis - Service d'Oncologie médicale; 🇫🇷 Rennes cedex, France

ICO - Site René Gauducheau - Service d'Oncologie medicale; 🇫🇷 SAINT-HERBLAIN Cedex, 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; 🇩🇪 Mönchengladbach, Germany

Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie; 🇩🇪 Halle, Sachsen Anhalt, Germany

Universitaetsklinikum Essen - Westdeutsches Tumorzentrum; 🇩🇪 Essen, Germany

Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2; 🇩🇪 Frankfurt, Germany

Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie; 🇩🇪 Muenster, Germany

Universitaetsklinikum Tuebingen - Klinik fuer Urologie; 🇩🇪 Tuebingen, 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; 🇮🇹 Firenze, Italy

IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia; 🇮🇹 Forli, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria; 🇮🇹 Milano, Italy

Ospedale San Raffaele - U.O. di Oncologia Medica; 🇮🇹 Milano, Italy

Humanitas Istituto Clinico Catanese - Oncologia Medica; 🇮🇹 Misterbianco, Italy

Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A; 🇮🇹 Napoli, Italy

Istituto Nazionale Tumori Regina Elena IRCCS - Urologia; 🇮🇹 Napoli, 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, Korea, Republic of

National Cancer Center; 🇰🇷 Gyeonggi-do, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea, Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

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; 🇪🇸 Cordoba, 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, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

Chi Mei Hospital, Liouying; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital,Linkou; 🇨🇳 Taoyuan, Taiwan

Barts Hospital - Dept of Medical Oncology; 🇬🇧 London, Greater London, United Kingdom

The Christie Hospital - Dept of Oncology; 🇬🇧 Manchester, United Kingdom

Royal Preston Hospital - Rosemere Cancer Centre; 🇬🇧 Preston, United Kingdom