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

Locally Advanced or Metastatic Urothelial Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327530
• Other study ID #: MS100070_0119
• Secondary ID: 2021-003669-36
• Status: Recruiting
• Phase: Phase 2
• Start date: August 17, 2022
• Est. completion date: January 23, 2025

Study information

• Verified date: January 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 252
• Est. completion date: January 23, 2025
• Est. primary completion date: January 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Exclusion Criteria:

• Participants with prior immunotherapy with Interleukin-2 (IL-2), IL-15, interferon alfa (IFN-a), 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Locally Advanced or Metastatic Urothelial Carcinoma

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Monash Medical Centre Clayton	Clayton
Australia	Sunshine Hospital - PARENT	Footscray
Australia	Austin Health	Heidelberg
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	Royal North Shore Hospital - PARENT	St Leonards
Australia	Macquarie University Hospital - PARENT	Sydney
Australia	The Kinghorn Can Cen	Westmead
Belgium	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	Wuerzburg
Canada	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
Denmark	Ålborg Universitets Hospital - onkologisk afd	Åalborg
Denmark	Sjællands University Hospital - PARENT (Næstved)	Naestved
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
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	Kliniken Maria Hilf GmbH - Klinik fuer Urologie	Muenchen	Nordrhein Westfalen
Germany	Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie	Muenster
Germany	Universitaetsklinikum Tuebingen - Klinik fuer Urologie	Tuebingen
Greece	Athens Medical Center	Athens
Greece	General Hospital of Athens "Alexandra"	Athens
Greece	University General Hospital "Attikon"	Athens
Greece	Euromedica General Clinic of Thessaloniki	Thessaloniki
Italy	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	Azienda Ospedaliera San Camillo Forlanini - Dipartimento di Oncologia Medica	Roma
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
Korea, Republic of	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
Spain	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	Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica	Valencia
Spain	Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica	Valencia
Taiwan	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	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital,Linkou	Taoyuan
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	The Christie Hospital - Dept of Oncology	Manchester
United Kingdom	Royal Preston Hospital - Rosemere Cancer Centre	Preston
United States	Johns Hopkins University	Baltimore	Maryland
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Beacon Cancer Care	Coeur d'Alene	Idaho
United States	Inova Schar Cancer Institute	Falls Church	Virginia
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	University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)	Kansas City	Kansas
United States	University of Wisconsin Cancer Center	Madison	Wisconsin
United States	Washington University	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Multicare Health System Tacoma General Hospital	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Greece,  Italy,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall Survival (OS)		Time from randomization of study drug until death, assessed approximately up to 51 months
Secondary	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
Secondary	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
Secondary	Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255		Pre-dose up to safety follow up, assessed approximately up to maximum 51 months
Secondary	Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255		Baseline up to 51 months
Secondary	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

External Links

•   Trial Awareness and Transparency website