Mobocertinib in non-small cell lung cancer

Abstract

Tyrosine kinase inhibitors (TKIs) have provided great benefit for patients with EGFR-mutant non-small cell lung cancer (NSCLC). While prior TKIs have demonstrated limited efficacy against exon 20 insertion mutations of EGFR (EGFR Ex20Ins), mobocertinib (TAK-788) is designed to specifically inhibit these Ex20Ins mutations. In a phase I/II clinical trial, mobocertinib demonstrated meaningful benefits among a cohort of platinum-pretreated patients with EGFR Ex20Ins mutant NSCLC. For this cohort, the objective response rate was 28% (95% confidence interval [CI], 20%-37%). The median progression-free survival and duration of response were 7.3 months (95% CI, 5.5-9.2) and 17.5 months (95% CI, 7.4-20.3), respectively, both by independent review committee assessment. On the basis of these results, mobocertinib was granted accelerated approval as the first TKI for treatment of this indication by the U.S. Food and Drug Administration (FDA) in 2021. This review summarizes the preclinical development of mobocertinib and the early-phase clinical data leading to its approval and discusses potential directions for mobocertinib's development.

Keywords: EGFR (Ex20Ins mutant) inhibitors; HER2 (Ex20Ins mutant) inhibitors; Mobocertinib; Non-small cell lung cancer; Solid tumor therapy.