EGFR ex20ins-specific tyrosine kinase inhibitor, Treatment for non-small cell lung cancer

Epidermal growth factor receptor (EGFR) exon 20 insertion driver mutations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and limited treatment options. These mutations are resistant to previously approved EGFR tyrosine kinase inhibitors that transformed the treatment landscape and improved outcomes for patients with NSCLC harboring the most common EGFR mutations, exon 19 deletions and L858R substitutions. Developing effective targeted therapies for patients with NSCLC harboring EGFR exon 20 insertion mutations is a critical need in lung cancer care. Mobocertinib is a novel, orally administered, first-in-class tyrosine kinase inhibitor that has demonstrated safety and efficacy against EGFR exon 20 insertion-mutated NSCLC in the phase I/II EXCLAIM trial. Findings from the study identified an objective response rate of 28% with median duration of response of 17.5 months following platinum-based chemotherapy, prompting the Food and Drug Administration to grant accelerated approval to mobocertinib in September 2021. This review details the published preclinical and clinical data for mobocertinib in treating NSCLC with EGFR exon 20 insertion mutations. We describe the toxicity profile of mobocertinib, provide clinical recommendations for treatment administration and toxicity management, and compare the efficacy of mobocertinib to that of other EGFR exon 20 insertion-targeted therapies in the pipeline.