K. Papadopoulos, F. Tsai, T. Bauer
May 30, 2017
Citations
1
Influential Citations
31
Citations
Journal
Journal of Clinical Oncology
Abstract
3005Background: Arginase is secreted by myeloid-derived suppressor cells (MDSCs) and polymorphonuclear cells (PMNs) in the tumor microenvironment, depleting arginine, an amino acid required for T-cell activation and proliferation. CB-1158 is an oral small molecule inhibitor of arginase. CB-1158 reverses PMN- and MDSC-mediated suppression of T-cells in ex vivo human models, and increases plasma and tumor arginine levels in mouse syngeneic tumor models leading to increased pro-inflammatory markers and activated CD8 T-cells in the tumor. CB-1158 has single agent efficacy in mouse tumor models and synergistically enhances the antitumor efficacy of checkpoint inhibitors. Methods: This is an ongoing phase 1 study to evaluate safety and tolerability of CB-1158 as a monotherapy and in combination with anti-PD-1 in pts with solid tumors. Pharmacokinetics (PK), anti-tumor effects, and biomarkers, including plasma arginine, arginase activity, and effects on immune function in blood and in tumors will be evaluated. C...