493TiP A CRUK phase I/IIA, first in human dose-escalation and expansion trial of HMBD-001 (an anti-HER-3 antibody) in patients with advanced HER3-positive solid tumours

Abstract

Human epidermal growth factor receptor (HER)3 is a member of the HER family of transmembrane proteins. HER3 lacks kinase activity and must be transactivated by dimerisation with a kinase-active partner for signal transduction. In ligand-dependent activation, the NRG1 ligand can stabilise HER3 in the open conformation. However, ligand-independent heterodimerization can also occur. Overexpression of HER3 is observed in multiple tumour types and associated with poor clinical outcome. HMBD-001 is an IgG1 humanized monoclonal antibody specifically targeting HER3 with a novel mechanism of action.