Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications

Abstract

Substantial therapeutic advancements have been made in identifying and treating activating mutations in advanced non -small cell lung cancer (NSCLC); however, resistance to epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) inhibitors remains common with current targeted therapies. Amivantamab, a fully human bispecific antibody targeting EGFR and MET, is approved in the United States and other countries for the treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations, for whom disease has progressed on or after platinum-based chemotherapy. Preliminary efficacy and safety have also been demonstrated in patients with common EGFR-or MET-mutated NSCLC. Amivantamab employs 3 distinct potential mechanisms of action (MOAs) including ligand blocking, receptor degradation, and immune cell-directing activity, such as antibody-dependent cellular cytotoxi-city and trogocytosis. Notably, efficacy with amivantamab does not require all 3 MOAs to occur simultaneously, broad-ening applicability by using diverse antitumor mechanisms. This review focuses on the molecular characteristics of amivantamab and its unique MOAs leading to in vitro and in vivo efficacy and safety in preclinical and clinical studies.Clinical Lung Cancer, Vol. 24, No. 2, 89-97 (c) 2022 The Authors. Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )