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ABSTRACT Introduction Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations following progression on chemotherapy, marking a watershed moment for a class of mutations which is generally associated with poor outcomes. Areas covered In this article, we outline the drug profile of amivantamab compared with EGFR kinase inhibitors under evaluation in EGFR exon 20 insertion mutant NSCLC. We also review the efficacy and safety data reported from the CHRYSALIS phase I trial, which forms the basis of the recent approval of amivantamab. Expert opinion Unlike small molecule EGFR kinase inhibitors, amivantamab has an extracellular mode of action and dual activity against EGFR and MET. It remains to be determined what role MET inhibition plays in toxicity and efficacy and whether dual target inhibition can delay the onset of drug resistance in these cancers. Due to its large molecular size, amivantamab is expected to have poor activity to treat brain metastases. Building on the clinical data so far, future trials that will evaluate combination treatments with brain-penetrant EGFR kinase inhibitors will be critical to move the drug toward a first-line treatment.