A randomized phase II study of atezolizumab plus recombinant human IL-7 (CYT107) or atezolizumab alone in patients with locally advanced or metastatic urothelial carcinoma (mUC): A Cancer Immunotherapy Trials Network Trial (CITN-14).

Evan Y. Yu University of Washington, Seattle, WA info_outline Evan Y. Yu, Steven Fling, Bob Salim, Randy F. Sweis, Gurkamal S. Chatta, Rohit K. Jain, Scott Edward Delacroix, Helen Moon, Andreanne Lacroix, Judith C Kaiser, Elad Sharon, Martin A. Cheever, Russell Pachynski

Authors Evan Y. Yu University of Washington, Seattle, WA info_outline Evan Y. Yu, Steven Fling, Bob Salim, Randy F. Sweis, Gurkamal S. Chatta, Rohit K. Jain, Scott Edward Delacroix, Helen Moon, Andreanne Lacroix, Judith C Kaiser, Elad Sharon, Martin A. Cheever, Russell Pachynski Organizations University of Washington, Seattle, WA, Fred Hutchinson Cancer Research Center, Seattle, WA, Axio Research, Seattle, WA, The University of Chicago, Chicago, IL, Roswell Park Comprehensive Cancer Center, Buffalo, NY, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, Louisiana State Univ School of Medcn and Stanley S. Scott Cancer Ctr, New Orleans, LA, SCPMG-Kaiser, Riverside, CA, National Cancer Institute, Bethesda, MD, Division of Oncology, Washington University Medical School, St. Louis, MO Abstract Disclosures Research Funding U.S. National Institutes of Health Pharmaceutical/Biotech Company 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 H 0 14.8% and H A 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