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

Phase 2

Active, not recruiting

• Conditions: Locally Advanced or Metastatic Urothelial Carcinoma
• Interventions: Drug: Avelumab; Drug: NKTR-255; Drug: Sacituzumab Govitecan; Drug: M6223

• Registration Number: NCT05327530
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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 available

Study Timeline

• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-04-13
• Study First Posted: 2022-04-14
• Study Start: 2022-08-17
• Primary Completion: 2025-06-20
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-14
• Last Update Posted: 2025-10-15
• Study Completion: 2026-06-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 256

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group D: Avelumab + NKTR-255	NKTR-255	-
Group B: Avelumab + Sacituzumab Govitecan	Sacituzumab Govitecan	-
Group C: Avelumab + M6223	M6223	-
Group A: Avelumab	Avelumab	-
Group B: Avelumab + Sacituzumab Govitecan	Avelumab	-
Group C: Avelumab + M6223	Avelumab	-
Group D: Avelumab + NKTR-255	Avelumab	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator	Time from randomization of study drug up to 51 months
Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255	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	Baseline up to 51 months
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator	Time from first documented objective response to PD or death due to any cause, assessed approximately 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	Baseline, Week 13
Overall Survival (OS)	Time from randomization of study drug until death, assessed approximately up to 51 months

Trial Locations

Locations (95)

Beacon Cancer Care; 🇺🇸 Coeur d'Alene, Idaho, United States

University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN); 🇺🇸 Kansas City, Kansas, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

The Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company - Kansas City, MO at St. Joseph Medical Center; 🇺🇸 Kansas City, Missouri, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Multicare Health System Tacoma General Hospital; 🇺🇸 Tacoma, Washington, United States

University of Wisconsin Cancer Center; 🇺🇸 Madison, Wisconsin, United States

Flinders Medical Centre; 🇦🇺 Bedford Park, Australia

Sunshine Hospital - PARENT; 🇦🇺 Footscray, Australia

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