A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)
- Conditions
- Therapeutic area: Diseases [C] - Neoplasms [C04]Advanced or metastatic urothelial carcinoma whose disease did not progress with 1L platinum-containing chemotherapy.
- Registration Number
- CTIS2023-510139-12-00
- Lead Sponsor
- Merck Healthcare KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
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
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
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate PFS of maintenance treatment with avelumab treatment combination regimens compared to maintenance avelumab monotherapy.;Secondary Objective: To evaluate OS of maintenance treatment with avelumab combination regimens compared to maintenance avelumab monotherapy followed by subsequent anticancer treatment., To evaluate OR of maintenance treatment with avelumab combination regimens compared to maintenance avelumab monotherapy., To evaluate DoR of maintenance treatment with avelumab combination regimens compared to maintenance avelumab monotherapy.;Primary end point(s): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator, 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]
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Overall Survival (OS);Secondary end point(s):Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator;Secondary end point(s):Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 Assessed by Investigator;Secondary end point(s):Pharmacokinetic Serum Concentration of Avelumab, M6223, Sacituzumab govitecan and NKTR255;Secondary end point(s):Number of Participants with Positive Anti-Drug Antibody (ADA) of Avelumab, M6223, Sacituzumab govitecan and NKTR-255;Secondary end point(s):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