HER2抑制剂ONT-380在HER2(+)晚期实体瘤患者中的I期研究，HER2(+)转移性乳腺癌(MBC)的扩展队列。
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Moulder SL, Borges VF, Baetz T, Mcspadden T, Fernetich G, Murthy RK, Chavira R, Guthrie K, Barrett E, Chia SK
HER2抑制剂ONT-380在HER2(+)晚期实体瘤患者中的I期研究，HER2(+)转移性乳腺癌(MBC)的扩展队列。
临床癌症杂志2017年7月15日;23(14):3529-3536。doi: 10.1158 / 1078 - 0432. - ccr - 16 - 1496。Epub 2017 1月4日。
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28053022 (PubMed视图］
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用途:ONT-380 (ary -380)是一种有效的选择性口服HER2抑制剂。这项I期研究确定了ONT-380在HER2阳性晚期实体瘤中的MTD、药代动力学(PK)和抗肿瘤活性，并对HER2(+) MBC患者进行了扩展队列研究。实验设计:ONT-380每天两次(BID)，连续28天为一个周期。在修改后的3+3剂量递增设计确定MTD后，纳入扩展队列。测定了ONT-380及其代谢产物的PK性质。采用实体瘤疗效评价标准(RECIST)评价疗效。结果:50例患者接受ONT-380治疗(升级= 33;膨胀= 17);43例患者为HER2(+) MBC。既往抗癌方案的中位数= 5。转氨酶增加的剂量限制毒性发生在800 mg BID时，因此600 mg BID为MTD。常见的不良事件严重程度通常为1/2级，包括恶心(56%)、腹泻(52%)、疲劳(50%)、呕吐(40%)、便秘、四肢疼痛和咳嗽(各20%)。 5 patients (19%) treated at MTD had grade 3 AEs (increased transaminases, rash, night sweats, anemia, and hypokalemia). The half-life of ONT-380 was 5.38 hours and increases in exposure were approximately dose proportional. In evaluable HER2(+) MBC (n = 22) treated at doses >/= MTD, the response rate was 14% [all partial response (PR)] and the clinical benefit rate (PR + stable disease >/= 24 weeks) was 27%.Conclusions: ONT-380 had a lower incidence and severity of diarrhea and rash than that typically associated with current dual HER2/EGFR inhibitors and showed notable antitumor activity in heavily pretreated HER2(+) MBC patients, supporting its continued development. Clin Cancer Res; 23(14); 3529-36. (c)2017 AACR.
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药物 酶 种类 生物 药理作用 行动 Tucatinib 受体酪氨酸蛋白激酶erbB-2 蛋白质 人类 未知的抑制剂细节