P-169 A first-in-human phase Ia/b, open-label, multicentre, dose-escalation study of BI 905711 in patients with advanced gastrointestinal cancers

Abstract

Activation of the tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAILR2) induces apoptosis via caspase activation. Hence, targeting TRAILR2 is an attractive therapeutic strategy; however, early trials of TRAILR2 agonists resulted, in some cases, in severe hepatotoxicity that may have been due to TRAILR2 activation on hepatocytes. Cadherin 17 (CDH17), a membrane protein highly expressed in gastrointestinal (GI) cancers, is not expressed in normal hepatic cells. Thus, the hepatotoxicity of prior TRAILR2 agonists may be avoided through crosslinking with CDH17.