盐酸恩沙替尼胶囊的药理与临床评价

Pharmacology and Clinical Evaluation of Ensartinib Hydrochloride Capsule

肺癌是全世界发病率和致死率最高的恶性肿瘤,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌的85%。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)重排阳性的NSCLC仅占全部NSCLC的5%,但预后较差,因此积极的治疗非常迫切。盐酸恩沙替尼胶囊(ensartinib hydrochloride capsule,X-396,商品名贝美纳TM)是第二代ALK抑制剂,对ALK的抑制活性和肺癌中枢神经系统转移的有效性较克唑替尼更强,并且可抑制多个克唑替尼耐药突变位点,临床拟用于治疗克唑替尼耐药的ALK阳性NSCLC。文中对盐酸恩沙替尼胶囊在国内外开展的I期-III期临床试验进行了总结,并对其药理作用、药代动力学和药效学、临床疗效和安全性评价进行了综述。

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide,and non-small cell lung cancer(NSCLC)accounts for about 85%.Only 5%NSCLC patients are anaplastic lymphoma kinase(ALK)rearrangement positive NSCLC,but the prognosis of these patients is poor,and treatment is urgent.Ensartinib(X-396),a next-generation ALK tyrosine kinase inhibitor(ALK-TKI),has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib,which is indicated for the treatment of crizotinib-resistant,ALKpositive NSCLC patients.Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad.In this review,we briefly summarized the results of these trials,and preliminary efficacy,safety,pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.