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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05327530




Registration number
NCT05327530
Ethics application status
Date submitted
5/04/2022
Date registered
14/04/2022

Titles & IDs
Public title
A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)
Scientific 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)
Secondary ID [1] 0 0
2021-003669-36
Secondary ID [2] 0 0
MS100070_0119
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic Urothelial Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Drugs - Sacituzumab Govitecan
Treatment: Drugs - M6223
Treatment: Drugs - NKTR-255

Experimental: Group A: Avelumab -

Experimental: Group B: Avelumab + Sacituzumab Govitecan -

Experimental: Group C: Avelumab + M6223 -

Experimental: Group D: Avelumab + NKTR-255 -


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
Timepoint [1] 0 0
Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months
Primary outcome [2] 0 0
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]
Timepoint [2] 0 0
From Randomization up to the last safety follow-up visit at approximately up to 51 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Time from randomization of study drug until death, assessed approximately up to 51 months
Secondary outcome [2] 0 0
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
Timepoint [2] 0 0
Time from randomization of study drug up to 51 months
Secondary outcome [3] 0 0
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator
Timepoint [3] 0 0
Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months
Secondary outcome [4] 0 0
Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255
Timepoint [4] 0 0
Pre-dose up to safety follow up, assessed approximately up to maximum 51 months
Secondary outcome [5] 0 0
Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255
Timepoint [5] 0 0
Baseline up to 51 months
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline, Week 13

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/01/2025
Actual
Sample size
Target
Accrual to date
Final
256
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Monash Medical Centre Clayton - Clayton
Recruitment hospital [3] 0 0
Sunshine Hospital - PARENT - Footscray
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [6] 0 0
Liverpool Hospital - PARENT - Liverpool
Recruitment hospital [7] 0 0
Calvary Mater Newcastle - PARENT - Newcastle
Recruitment hospital [8] 0 0
Tasman Oncology Research Ltd - Oncology - Southport
Recruitment hospital [9] 0 0
Royal North Shore Hospital - PARENT - St Leonards
Recruitment hospital [10] 0 0
Macquarie University Hospital - PARENT - Sydney
Recruitment hospital [11] 0 0
The Kinghorn Can Cen - Westmead
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Footscray
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment postcode(s) [5] 0 0
- Kurralta Park
Recruitment postcode(s) [6] 0 0
- Liverpool
Recruitment postcode(s) [7] 0 0
- Newcastle
Recruitment postcode(s) [8] 0 0
- Southport
Recruitment postcode(s) [9] 0 0
- St Leonards
Recruitment postcode(s) [10] 0 0
- Sydney
Recruitment postcode(s) [11] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Idaho
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United States of America
State/province [2] 0 0
Illinois
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United States of America
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Kansas
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United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Belgium
State/province [9] 0 0
Antwerpen
Country [10] 0 0
Belgium
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Brasschaat
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Kortrijk
Country [14] 0 0
Belgium
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Libramont
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Belgium
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Liege
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Belgium
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Wuerzburg
Country [17] 0 0
Canada
State/province [17] 0 0
Brampton
Country [18] 0 0
Canada
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Greenfield Park
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Canada
State/province [19] 0 0
Montreal
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Canada
State/province [20] 0 0
Ottawa
Country [21] 0 0
Denmark
State/province [21] 0 0
Naestved
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Denmark
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Åalborg
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France
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Hauts De Seine
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France
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Angers cedex 2
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France
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Bordeaux Cedex
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France
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Caen CEDEX
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France
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Creteil
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France
State/province [28] 0 0
Le Mans
Country [29] 0 0
France
State/province [29] 0 0
Lyon
Country [30] 0 0
France
State/province [30] 0 0
Marseille Cedex 5
Country [31] 0 0
France
State/province [31] 0 0
Nîmes
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Poitiers Cedex
Country [34] 0 0
France
State/province [34] 0 0
Rennes cedex
Country [35] 0 0
France
State/province [35] 0 0
SAINT-HERBLAIN Cedex
Country [36] 0 0
France
State/province [36] 0 0
Strasbourg
Country [37] 0 0
Germany
State/province [37] 0 0
Nordrhein Westfalen
Country [38] 0 0
Germany
State/province [38] 0 0
Sachsen Anhalt
Country [39] 0 0
Germany
State/province [39] 0 0
Essen
Country [40] 0 0
Germany
State/province [40] 0 0
Frankfurt
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Germany
State/province [41] 0 0
Halle
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Germany
State/province [42] 0 0
Muenster
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Germany
State/province [43] 0 0
Mönchengladbach
Country [44] 0 0
Germany
State/province [44] 0 0
Tuebingen
Country [45] 0 0
Greece
State/province [45] 0 0
Athens
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Greece
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Thessaloniki
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Italy
State/province [47] 0 0
Bologna
Country [48] 0 0
Italy
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Firenze
Country [49] 0 0
Italy
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Forli
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Italy
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Milano
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Italy
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Misterbianco
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Italy
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Napoli
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Italy
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Padova
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Italy
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Pisa
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Italy
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Ravenna
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Italy
State/province [56] 0 0
Roma
Country [57] 0 0
Italy
State/province [57] 0 0
Rome
Country [58] 0 0
Italy
State/province [58] 0 0
San Giovanni Rotondo
Country [59] 0 0
Italy
State/province [59] 0 0
Terni
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Daejeon
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Korea, Republic of
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Gyeonggi-do
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Seongnam-si
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Korea, Republic of
State/province [63] 0 0
Seoul
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Spain
State/province [64] 0 0
Badajoz
Country [65] 0 0
Spain
State/province [65] 0 0
Barcelona
Country [66] 0 0
Spain
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Cordoba
Country [67] 0 0
Spain
State/province [67] 0 0
Elche
Country [68] 0 0
Spain
State/province [68] 0 0
Lugo
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
Spain
State/province [70] 0 0
Manresa
Country [71] 0 0
Spain
State/province [71] 0 0
Valencia
Country [72] 0 0
Taiwan
State/province [72] 0 0
Kaohsiung
Country [73] 0 0
Taiwan
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Taichung
Country [74] 0 0
Taiwan
State/province [74] 0 0
Tainan
Country [75] 0 0
Taiwan
State/province [75] 0 0
Taipei City
Country [76] 0 0
Taiwan
State/province [76] 0 0
Taipei
Country [77] 0 0
Taiwan
State/province [77] 0 0
Taoyuan
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Greater London
Country [79] 0 0
United Kingdom
State/province [79] 0 0
London
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Manchester
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
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
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://bit.ly/IPD21


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05327530