LAUSR

TPS4586 Background: Atezolizumab is a regulatory-approved PD-L1 antagonistic antibody for the post-platinum mUC setting. Responses to atezolizumab are highly efficacious in a subset of patients, but suboptimal or absent in most patients. IL-7 (CYT107) is a homeostatic growth factor that promotes proliferation, differentiation, and survival of T lymphocytes. We recently demonstrated CYT107 significantly increases peripheral absolute lymphocyte and T cell numbers in metastatic castration-resistant prostate cancer patients when administered after sipuleucel-T. We hypothesize expansion of T cells by CYT107 may improve responses to PD-L1 inhibition. To test this hypothesis, we designed a randomized trial (NCT03513952) in mUC comparing the combination of CYT107 and atezolizumab to atezolizumab alone. Methods: Patients with ECOG PS ≤2 and RECIST v1.1 measurable mUC with disease recurrence after platinum-based chemotherapy are eligible. A safety run-in of 6 patients with staggered enrollment to atezolizumab plus CYT107 will be followed by randomization if <2 patients experience a DLT. An additional 48 patients will then be randomized 1:1 to atezolizumab 1200 mg IV q3wks with or without CYT107 10 ug/kg IM qwk X 4, started 1 wk before atezolizumab. The primary endpoint is RECIST v1.1 ORR, with H0 14.8% and HA 45%, one-sided α 0.10; power 88%. An interim futility analysis will be performed after 24 randomized patients have their first disease assessment; cessation of the trial will occur if an O’Brien-Fleming futility boundary of <-0.0063 in the ORR scale is observed between the experimental and control arm. Secondary endpoints include clinical benefit rate, PFS, DOR, OS, results by PD-L1 expression stratification, and safety. Exploratory correlative evaluations of tumor-infiltrating immune cells, interferon γ expression, inflammatory gene expression, ELISPOT, T cell receptor sequencing, serum metabolite levels, gut microbiome, and PK analyses will be performed. Current state: Trial accrual has begun and is anticipated to complete around mid-2020. Clinical trial information: NCT03513952.