Anti-EGFR-Anti-c-Met Bispecific Antibody (Amivantamab)

Anti-EGFR-Anti-c-Met Bispecific Antibody is a purified recombinant human bispecific antibody targeting EGFR (epidermal growth factor receptor) and c-Met. It is also known as Amivantamab, and being studied for the treatment of patients with NSCLC (non-small cell lung cancer) that have EGFR exon 20 mutations. EGFR (epidermal growth factor receptor), also known as ERBB-1 and HER1, is the cell-surface tyrosine kinase receptor for members of the epidermal growth factor family. Its ligands include EGF, TGFalpha (transforming growth factor alpha), HB-EGF (heparin-binding EGF), betacellulin, amphiregulin, epiregulin, and epigen. EGFR exists in basal states as an inactive monomer. EGFR can bind to several adaptor proteins simultaneously and thus activate multiple positive and negative signaling pathways. Overexpression and/or hyperactivation of EGFR kinase is associated with several human cancers such as lung, glioblastoma (GBM), and epithelial tumors of the neck and head. Mutations in EGFR can result in constitutive activation, allowing tumor cell proliferation and development of resistance to therapy. Its role in cancer has led to the development of anticancer therapeutics targeting EGFR. There are several clinically approved inhibitors, such as Erlotinib and Gefitinib, for the treatment of NSCLC (non-small cell lung cancer) and pancreatic cancer. In addition, several monoclonal antibodies have been approved, such as Cetuximab. Patients that respond to anti-EGFR therapy tend to develop resistance, highlighting the need for further studies and new therapeutic avenues. The use of bispecific antibodies, such as Amivantamab, targeting both EGFR and c-Met leads to receptor degradation and ADCC (antibody dependent cellular cytotoxicity), and has been cleared by the FDA for the treatment of patients with NSCLC that have EGFR exon 20 mutations.