第一阶段研究Ceritinib (LDK378)患者在日本先进,间变性淋巴瘤Kinase-Rearranged非小细胞肺癌或其他肿瘤。

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西,村上H, Horiike,高桥T,平井一夫F, Suenaga N,日本田岛T, Tokushige K, Ishii M,碳化硼铝,罗布森M,濑户T

第一阶段研究Ceritinib (LDK378)患者在日本先进,间变性淋巴瘤Kinase-Rearranged非小细胞肺癌或其他肿瘤。

J Thorac杂志。2015;10 (7):1058 - 66。doi: 10.1097 / JTO.0000000000000566。

PubMed ID

26020125 (在PubMed

]

文摘

简介:间变性淋巴瘤激酶(碱性)重新安排非小细胞肺癌(NSCLC)筛选抑制剂敏感,但抗性的发展。本研究评估了最大耐受剂量、安全性、药物动力学(PK),和ceritinib的抗肿瘤活性,小说筛选抑制剂(乙醇),在日本ALK-rearranged恶性肿瘤患者。方法:这个阶段我、多中心、非盲研究(NCT01634763)招收成人患者ALK-rearranged(通过荧光原位杂交和/或免疫组织化学)局部晚期或转移性恶性肿瘤的进展,尽管标准治疗。这项研究包括两个部分:剂量升级和剂量的扩张。Ceritinib(单剂)的口服药物在为期三天的PK试车期间,每天一次,在21天的周期。自适应剂量升级是由贝叶斯模型。结果:20例患者(80%乙醇处理历史(ALKi-pretreated);19日非小细胞肺癌;一个炎症肿瘤染色法)收到ceritinib 300到750毫克(19剂量升级期间,一个在剂量扩张)。增加两个dose-limiting毒性发生:三年级脂肪酶(600毫克); grade 3 drug-induced liver injury (750 mg). The most common adverse events were gastrointestinal (nausea: 95%; diarrhea, vomiting: 75%). Ceritinib PK profile was dose proportional across 300 to 750 mg dosages; steady state was reached by day 15. Overall response rate was 55% (11 of 20 patients). Among patients with NSCLC, partial response was observed in two of four ALKi-naive patients, five of nine crizotinib-pretreated patients, two of four alectinib-pretreated patients, and one of two crizotinib and alectinib/ASP3026 pretreated patients. The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response. CONCLUSIONS: Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing.

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药物

Ceritinib