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.

中文翻译：

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Mobocertinib 治疗非小细胞肺癌。

酪氨酸激酶抑制剂 (TKI) 为 EGFR 突变非小细胞肺癌 (NSCLC) 患者带来了巨大益处。虽然之前的 TKI 已证明对 EGFR (EGFR Ex20Ins) 外显子 20 插入突变的疗效有限，但 mobocertinib (TAK-788) 旨在特异性抑制这些 Ex20Ins 突变。在 I/II 期临床试验中，mobocertinib 在一组接受铂类治疗的 EGFR Ex20Ins 突变 NSCLC 患者中显示出有意义的益处。对于这个队列，客观反应率为 28%（95% 置信区间 [CI]，20%-37%）。根据独立审查委员会的评估，中位无进展生存期和反应持续时间分别为 7.3 个月（95% CI，5.5-9.2）和 17.5 个月（95% CI，7.4-20.3）。基于这些结果，