Metastatic Urothelial Carcinoma Clinical Trial
Official title:
A Randomized Phase II Study of Atezolizumab (MPDL3280A) Plus Recombinant Human IL7 (CYT107) in Patients With Locally Advanced or Metastatic Urothelial Carcinoma
This phase II trial studies how well atezolizumab when given with glycosylated recombinant human interleukin-7 (CYT107) works in treating patients with urothelial carcinoma that has spread to nearby tissue or lymph nodes (locally advanced), cannot be removed by surgery (inoperable), or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CYT107 is a biological product naturally made by the body that may stimulate the immune system to destroy tumor cells. Giving atezolizumab and CYT107 may work better in treating patients with locally advanced, inoperable, or metastatic urothelial carcinoma compared to atezolizumab alone.
PRIMARY OBJECTIVE: I. To determine the clinical efficacy of the investigational treatment combination. SECONDARY OBJECTIVES: I. To determine the clinical activity and toxicity of the investigational treatment combination. II. The clinical benefit rate (CBR), progression-free survival (PFS), duration of response (DOR), as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related (ir) RECIST, and overall survival (OS). III. The CBR, PFS, DOR, and OS in all patients and patients stratified by PD-L1 expression levels in the tumor microenvironment. IV. The safety and toxicity of addition of CYT107 to atezolizumab. EXPLORATORY OBJECTIVES: I. To determine the immune correlates of the clinical activity of the investigational treatment combination. II. Explore the effect of the investigational treatment combination on the number and phenotype of tumor-specific T cells in the peripheral blood. III. Investigate for evidence that the investigational treatment combination increases the exposure of bladder cancer-specific antigens (e.g., cancer/testis antigens or neoantigens). IV. Investigate changes in tumor microenvironment that correlate with response or provide information on potential actionable causes for lack of clinical benefit. V. Investigate the potential that administration of atezolizumab with CYT107 may perturb the pharmacokinetics and immunogenicity of CYT107. OUTLINE: Safety Run-in phase - patients assigned to the experimental arm (atezolizumab + CYT107). If the treatment combination of the experimental arm demonstrates an acceptable safety profile in the Safety Run-In (one or fewer patient experiences a protocol-defined Dose Limiting-Toxicity), randomized enrollment into the trial will begin. The Run-in phase patients will be analyzed and reported separately both for safety and for efficacy. Patients are randomized to 1 of 2 groups. GROUP 1 (experimental arm): Patients receive CYT107 intramuscularly (IM) on days 1, 8, 15, and 22, and atezolizumab intravenously (IV) over 60 minutes on day 8 of cycle 1. Following cycle 1, patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles with atezolizumab repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) scans, and collection of blood and stool samples on study. Patients may also undergo tumor biopsy at screening and on study. GROUP 2 (control arm): Patients receive atezolizumab IV over 60 minutes on cycle 1. Following cycle 1, patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI scans, and collection of blood and stool samples on study. Patients may also undergo tumor biopsy at screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 2 years. ;
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