First-in-human phase 1 single-dose study of TRX-518, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody in adults with advanced solid tumors.

Abstract

3017Background: TRX518 is a novel, fully humanized agylcosyl IgG1 anti-GITR mAb. GITR is a member of the tumor necrosis factor receptor family expressed on T, B, & NK cells, and antigen presenting cells. GITR is expressed at high levels by Tregs and up-regulated following T cell activation; minimally expressed by nazve CD4+ and CD8+ T cells. Signaling through GITR abrogates Treg mediated suppression and enhances CD4+ and CD8+ T cell proliferation and TCR stimulation. GITR signaling may enhance host immune responses against tumor and aid in tumor rejection. This study evaluated the safety of a single dose of TRX518 in pts with advanced refractory solid tumors. Methods: Pts received a single dose of TRX518 on Day 1; doses ranged from 0.0001 to 8 mg/kg in 9 cohorts of up to 6 pts/cohort. The study was to determine safety and tolerability, maximum tolerated dose (MTD), pharmacokinetic (PK), and pharmacodynamic (PD) profiles of TRX518. Efficacy was evaluated with the immune related response criteria (irRC). Re...