Clinical trial NCT05327530: A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
Keywords: Avelumab
Avelumab in combination
Bladder cancer
M6223 (anti-TIGIT antibody)
PD-L1
Sacituzumab govitecan (Trop-2 antibody drug conjugate)
NKTR-255 (IL-15 agonist)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
First posted: 2022-04-14
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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-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

Primary outcomes:
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
timeFrame: Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months
measure: 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]
timeFrame: From Randomization up to the last safety follow-up visit at approximately up to 51 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Time from randomization of study drug until death, assessed approximately up to 51 months
measure: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
timeFrame: Time from randomization of study drug up to 51 months
measure: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
timeFrame: Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months
measure: Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255
timeFrame: Pre-dose up to safety follow up, assessed approximately up to maximum 51 months
measure: Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255
timeFrame: Baseline up to 51 months
measure: 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
timeFrame: Baseline, Week 13
Other outcomes:
Locations:
city: Coeur d'Alene
country: United States
facility: Beacon Cancer Care
state: Idaho
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Kansas City
country: United States
facility: AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center
state: Missouri
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Tacoma
country: United States
facility: Multicare Health System Tacoma General Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Cancer Center
state: Wisconsin
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Footscray
country: Australia
facility: Sunshine Hospital - PARENT
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
city: Liverpool
country: Australia
facility: Liverpool Hospital - PARENT
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle - PARENT
city: Southport
country: Australia
facility: Tasman Oncology Research Ltd - Oncology
city: Sydney
country: Australia
facility: Macquarie University Hospital - PARENT
city: Westmead
country: Australia
facility: The Kinghorn Can Cen
city: Antwerpen
country: Belgium
facility: ZNA Middelheim - Middelheim - account 2
city: Brasschaat
country: Belgium
facility: AZ Klina - PARENT
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet - Medical Oncology
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - Medical Oncology
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Kennedylaan - account 2
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne - PARENT
city: Liege
country: Belgium
facility: CHU de Liège - PARENT
city: Wuerzburg
country: Belgium
facility: Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
city: Brampton
country: Canada
facility: William Osler Health System - Brampton Civic Hospital
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre - Hospital Charles Le Moyne
city: Montreal
country: Canada
facility: CHUM Centre de Recherche
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Suresnes Cedex
country: France
facility: Hôpital Foch - Service d'Oncologie Médicale
state: Hauts De Seine
city: Angers cedex 2
country: France
facility: ICO - Site Paul Papin - service d'oncologie medicale
city: Bordeaux Cedex
country: France
facility: Institut Bergonié - Service d'Oncologie Médicale
city: Caen CEDEX
country: France
facility: Centre François Baclesse - Pathologies Gynecologiques
city: Creteil
country: France
facility: Hôpital Henri Mondor - Service d'Oncologie Médicale
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard - Service d'Oncologie Médical
city: Lyon
country: France
facility: Centre Leon Berard - Service d'Oncologie Medicale
city: Marseille Cedex 5
country: France
facility: Hôpital de la Timone - service d'urologie
city: Nîmes
country: France
facility: Hopital Caremeau - Service Hématologie Clinique/Oncologie Médicale
city: Paris
country: France
facility: Hôpital Cochin - Hematologie et Oncologie Médicale
city: Poitiers Cedex
country: France
facility: CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
city: Rennes cedex
country: France
facility: CRLCC Eugene Marquis - Service d'Oncologie médicale
city: SAINT-HERBLAIN Cedex
country: France
facility: ICO - Site René Gauducheau - Service d'Oncologie medicale
city: Strasbourg
country: France
facility: Clinique Sainte-Anne - Service d'Oncologie Médicale
city: Strasbourg
country: France
facility: Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
city: Muenchen
country: Germany
facility: Kliniken Maria Hilf GmbH - Klinik fuer Urologie
state: Nordrhein Westfalen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale) - Universitaetsklinik und Poliklinik fuer Urologie
state: Sachsen Anhalt
city: Essen
country: Germany
facility: Universitaetsklinikum Essen - Westdeutsches Tumorzentrum
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt Goethe-Universitaet - Urologie und Kinderurologie2
city: Halle
country: Germany
facility: Universitaetsklinikum Wuerzburg - Klinik u. Poliklinik f. Urologie u. Kinderurologie
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster - Klinik und Poliklinik fuer Urologie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH - Klinik fuer Urologie
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen - Klinik fuer Urologie
city: Athens
country: Greece
facility: Athens Medical Center
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Athens
country: Greece
facility: University General Hospital "Attikon"
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi - S.O.D. di Oncologia Medica
city: Forli
country: Italy
facility: IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST - Oncologia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori - S.S. Oncologia Medica Genitourinaria
city: Milano
country: Italy
facility: Ospedale San Raffaele - U.O. di Oncologia Medica
city: Misterbianco
country: Italy
facility: Humanitas Istituto Clinico Catanese - Oncologia Medica
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale - Oncologia Medica A
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Regina Elena IRCCS - Urologia
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza - Dipartimento di Oncologia Medica
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria Di Terni - S.C. Oncologia Medica
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina - Unidad de Fase I
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau - Dept of Oncology
city: Barcelona
country: Spain
facility: Hospital del Mar - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitario Virgen del Rocio - Oncology Service
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia - Dept of Oncology
city: Elche
country: Spain
facility: Hospital General Universitario de Elche - Servicio de Oncologia
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti - Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Manresa
country: Spain
facility: ALTHAIA, Xarxa assistencial Universitaria de Manresa - Oncology Dept
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital, Liouying
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital,Linkou
city: London
country: United Kingdom
facility: Barts Hospital - Dept of Medical Oncology
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie Hospital - Dept of Oncology
city: Preston
country: United Kingdom
facility: Royal Preston Hospital - Rosemere Cancer Centre
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: