Phase 3 study of patritumab plus erlotinib in EGFR wild-type subjects with advanced non-small cell lung cancer

• Many patients with advanced non–small cell lung cancer (NSCLC) initially benefit from treatment with anti–epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the secondor third-line setting,1-3 but subsequently develop resistance to this treatment • Human epidermal growth factor receptor 3 (HER3) is a key dimerization partner of HER family members (including EGFR) and is involved with activating downstream oncogenic signaling pathways4 • Constitutive HER3 signaling is associated with high expression of the HER3 ligand heregulin (HRG)5 and HRG has been shown to be important for tumor growth and proliferation, including in NSCLC cell lines6 • Research indicates that upregulation and reactivation of HER3 functions as an escape mechanism from EGFR inhibition, and may play a role in tumor resistance to EGFR TKIs,7-10 while HRG has been found to reverse sensitivity to EGFR inhibitors in preclinical models11 • Patritumab is a fully human anti-HER3 monoclonal antibody that binds to the extracellular domain of HER3, promoting receptor internalization and degradation and inhibiting ligands from binding HER3 (including HRG)12-14 (Figure 1) 7910