BACKGROUND Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. It was developed by Roche and initially approved in Japan in 2019 to treat pediatric and adult patients with NTRK fusionpositive, recurrent, or advanced solid tumors. In August 2019, entrectinib received accelerated approval by the U.S FDA for this indication. It is also the first FDA-approved drug designed to target both NTRK and ROS1. OBJECTIVE We aim to summarize recent studies related to the synthesis, mechanism of action, and clinical trials of the newly approved selective tyrosine kinase inhibitor entrectinib. METHODS We conduct a literature review of the research studies on the new highly-potent small-molecule entrectinib. CONCLUSION Entrectinib, based on three clinical studies (ALKA, STARTRK-1, and STARTRK-2), was well tolerated, with a manageable safety profile. It induced clinically meaningful responses in recurrent or advanced solid tumors associated with NTRK fusion- positive or ROS1+ NSCLC. It demonstrated substantial efficacy in patients with CNS metastases.

中文翻译：

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Entrectinib：一种新的选择性酪氨酸激酶抑制剂，获准用于治疗 NTRK 融合阳性、复发性或晚期实体瘤的儿科和成人患者。

背景 Entrectinib 是一种高效的 ATP 竞争性和选择性酪氨酸激酶抑制剂 - Trk ABC、ALK 和 ROS1。它由罗氏公司开发，最初于 2019 年在日本获批，用于治疗 NTRK 融合阳性、复发性或晚期实体瘤的儿科和成人患者。2019年8月，恩曲替尼获得美国FDA对该适应症的加速批准。它也是 FDA 批准的第一个针对 NTRK 和 ROS1 的药物。目的我们旨在总结近期与新获批的选择性酪氨酸激酶抑制剂恩曲替尼的合成、作用机制和临床试验相关的研究。方法我们对新型高效小分子恩曲替尼的研究进行文献综述。结论 Entrectinib，基于三项临床研究（ALKA、STARTRK-1 和 STARTRK-2），耐受性良好，安全性可控。它在与 NTRK 融合阳性或 ROS1+ NSCLC 相关的复发性或晚期实体瘤中诱导了具有临床意义的反应。它在 CNS 转移患者中显示出显着的疗效。