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

• ClinicalTrials.gov Identifier: NCT05327530
• Recruitment Status: Recruiting
• First Posted: April 14, 2022
• Last Update Posted: October 5, 2022
• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics
• Information provided by (Responsible Party): EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information

• First Submitted Date: April 5, 2022
• First Posted Date: April 14, 2022
• Last Update Posted Date: October 5, 2022
• Actual Study Start Date: August 17, 2022
• Estimated Primary Completion Date: August 5, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2022)

• 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 ]
• 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: Randomization up to the last safety follow-up visit at approximately up to 51 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 13, 2022)

• Overall Survival (OS) [ Time Frame: Time from randomization of study drug until death, assessed approximately up to 51 months ]
• 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 ]
• 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 ]
• 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 ]
• Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255 [ Time Frame: Baseline up to 51 months ]
• 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, Month 51 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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)
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
  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 until unacceptable toxicity, withdraw consent or initiation of a new treatment.
• 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 until unacceptable toxicity, withdraw consent or initiation of a new treatment.
• 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) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Study Arms

• Experimental: Group A: Avelumab
  Intervention: Drug: Avelumab
• Experimental: Group B: Avelumab + Sacituzumab Govitecan
  Interventions:

  • Drug: Avelumab
  • Drug: Sacituzumab Govitecan
• Experimental: Group C: Avelumab + M6223
  Interventions:

  • Drug: Avelumab
  • Drug: M6223
• Experimental: Group D: Avelumab + NKTR-255
  Interventions:

  • Drug: Avelumab
  • Drug: NKTR-255

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 13, 2022): 252
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 24, 2026
• Estimated Primary Completion Date: August 5, 2026 (Final data collection date for primary outcome measure)

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, any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways, 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) and replication-deficient coronavirus vaccines approved or authorized by local Health Authorities
• Other protocol defined exclusion criteria could apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US Medical Information; 888-275-7376; eMediUSA@emdserono.com

Contact: Communication Center; +49 6151 72 5200; service@emdgroup.com

• Listed Location Countries: Australia, Belgium, Korea, Republic of, Spain, United States

Administrative Information

• NCT Number: NCT05327530
• Other Study ID Numbers: MS100070_0119; 2021-003669-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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

• Current Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: EMD Serono Research & Development Institute, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics

Investigators

• Study Director: Medical Responsible; Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

• PRS Account: EMD Serono
• Verification Date: October 2022