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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
Date last updated
4/11/2024

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
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [5] 0 0
Liverpool Hospital - PARENT - Liverpool
Recruitment hospital [6] 0 0
Calvary Mater Newcastle - PARENT - Newcastle
Recruitment hospital [7] 0 0
Tasman Oncology Research Ltd - Oncology - Southport
Recruitment hospital [8] 0 0
Macquarie University Hospital - PARENT - Sydney
Recruitment hospital [9] 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
- Kurralta Park
Recruitment postcode(s) [5] 0 0
- Liverpool
Recruitment postcode(s) [6] 0 0
- Newcastle
Recruitment postcode(s) [7] 0 0
- Southport
Recruitment postcode(s) [8] 0 0
- Sydney
Recruitment postcode(s) [9] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Idaho
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Brasschaat
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Belgium
State/province [11] 0 0
Kortrijk
Country [12] 0 0
Belgium
State/province [12] 0 0
Libramont
Country [13] 0 0
Belgium
State/province [13] 0 0
Liege
Country [14] 0 0
Belgium
State/province [14] 0 0
Wuerzburg
Country [15] 0 0
Canada
State/province [15] 0 0
Brampton
Country [16] 0 0
Canada
State/province [16] 0 0
Greenfield Park
Country [17] 0 0
Canada
State/province [17] 0 0
Montreal
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Canada
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Ottawa
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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
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Le Mans
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France
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Lyon
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France
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Marseille Cedex 5
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France
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Nîmes
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France
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Paris
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France
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Poitiers Cedex
Country [30] 0 0
France
State/province [30] 0 0
Rennes cedex
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France
State/province [31] 0 0
SAINT-HERBLAIN Cedex
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg
Country [33] 0 0
Germany
State/province [33] 0 0
Nordrhein Westfalen
Country [34] 0 0
Germany
State/province [34] 0 0
Sachsen Anhalt
Country [35] 0 0
Germany
State/province [35] 0 0
Essen
Country [36] 0 0
Germany
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Frankfurt
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Germany
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Halle
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Germany
State/province [38] 0 0
Muenster
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Germany
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Mönchengladbach
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Germany
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Tuebingen
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Greece
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Athens
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Greece
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Thessaloniki
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Italy
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Bologna
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Italy
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Firenze
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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
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Rome
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Italy
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San Giovanni Rotondo
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Italy
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Terni
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Korea, Republic of
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Daejeon
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
State/province [58] 0 0
Seoul
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Spain
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Badajoz
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Elche
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Spain
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Lugo
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Spain
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Madrid
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Spain
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Manresa
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei City
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taipei
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Taiwan
State/province [71] 0 0
Taoyuan
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Greater London
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Manchester
Country [74] 0 0
United Kingdom
State/province [74] 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
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 website
https://clinicaltrials.gov/study/NCT05327530
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05327530