Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations

被引:18
|
作者
Zhang, Shannon S. [1 ]
Zhu, Viola W. [1 ,2 ]
机构
[1] Univ Calif Orange, Irvine Sch Med, Dept Med, 200 S Manchester Ave,Suite 410, Orange, CA 92868 USA
[2] Chao Family Comprehens Canc Ctr, Orange, CA USA
关键词
mobocertinib; TAK-788; NSCLC; EGFR exon 20 insertion; TKI; amivantamab;
D O I
10.2147/LCTT.S307321
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The EGFR exon 20 insertion (EGFRex20ins) mutations are the third most common EGFR mutations seen in non-small cell lung cancer (NSCLC), constituting up to 12% of NSCLC cases harboring EGFR mutations.1 This molecular alteration is characterized by in-frame insertions and/or duplications clustered between codons 762 and 774, resulting in constitutive activation of the EGFR pathway.2,3 More than 50 variants of EGFRex20ins mutations have been identified with A767_V769dupASV (ASV) being the most common variant across multiple The EGFR exon 20 insertion (EGFRex20ins) mutations are the third most common EGFR mutations seen in non-small cell lung cancer (NSCLC). More than 50 variants of EGFRex20ins mutations have been identified with A767_V769dupASV being the most common variant across multiple surveys. Treatment with currently available EGFR tyrosine kinase inhibitors (TKIs) including osimertinib is generally ineffective. Amivantamab (JNJ-372), a bispecific monoclonal antibody against EGFR and MET, has recently been approved by the US FDA for patients with advanced or metastatic NSCLC harboring EGFRex20ins mutations after disease progression on platinum-based chemotherapy. Among all the TKIs in clinical development, mobocertinib (TAK-788) has been granted priority review by the FDA for the same indication as amivantamab. Here, we provide a concise review on mobocertinib, with a focus on its chemical structure, preclinical data, and phase 1/2 trial results. Future directions will likely focus on combination approach such as TKI plus chemotherapy in the first-line setting, designing drugs with CNS activity, and exploring disease characteristics of various EGFRex20ins mutation variants and how they may affect treatment response.
引用
收藏
页码:61 / 65
页数:5
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