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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05327530
Recruitment Status : Recruiting
First Posted : April 14, 2022
Last Update Posted : May 25, 2023
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Urothelial Carcinoma Drug: Avelumab Drug: Sacituzumab Govitecan Drug: M6223 Drug: NKTR-255 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 17, 2022
Estimated Primary Completion Date : August 5, 2026
Estimated Study Completion Date : August 24, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Group A: Avelumab 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.
Other Name: MSB0010718C
Experimental: Group B: Avelumab + Sacituzumab Govitecan 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.
Other Name: MSB0010718C

Drug: 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.
Experimental: Group C: Avelumab + M6223 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.
Other Name: MSB0010718C

Drug: 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.
Experimental: Group D: Avelumab + NKTR-255 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.
Other Name: MSB0010718C

Drug: 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.


Outcome Measures
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Primary Outcome Measures :
  1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator [ Time Frame: Time from randomization of study drug until first documentation of progressive disease (PD) or death, assessed approximately up to 51 months ]
  2. 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] [ Time Frame: From Randomization up to the last safety follow-up visit at approximately up to 51 months ]

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Time from randomization of study drug until death, assessed approximately up to 51 months ]
  2. Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator [ Time Frame: Time from randomization of study drug up to 51 months ]
  3. Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator [ Time Frame: Time from first documented objective response to PD or death due to any cause, assessed approximately up to 51 months ]
  4. Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255 [ Time Frame: Pre-dose up to safety follow up, assessed approximately up to maximum 51 months ]
  5. Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255 [ Time Frame: Baseline up to 51 months ]
  6. 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 [ Time Frame: Baseline, Week 13 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05327530


Contacts
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Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
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Additional Information:

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT05327530    
Other Study ID Numbers: MS100070_0119
2021-003669-36 ( EudraCT Number )
First Posted: April 14, 2022    Key Record Dates
Last Update Posted: May 25, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 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
Access Criteria: 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.
URL: http://bit.ly/IPD21

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Avelumab
Avelumab in combination
Bladder cancer
M6223 (anti-TIGIT antibody)
 PD-L1
Sacituzumab govitecan (Trop-2 antibody drug conjugate)
NKTR-255 (IL-15 agonist)
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Avelumab
 Sacituzumab govitecan
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs