Sacituzumab govitecan(方面- 132),一个anti-Trop-2-SN-38抗体药物共轭治疗不同的上皮癌:安全性和药物动力学。

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海洋AJ, Starodub,巴蒂亚Vahdat LT, Isakoff SJ, Guarino M,梅瑟史密斯对比佤邦,Picozzi VJ,梅耶尔IA,韦格纳佤邦,Maliakal P, Govindan SV,夏基RM,戈登伯格DM

Sacituzumab govitecan(方面- 132),一个anti-Trop-2-SN-38抗体药物共轭治疗不同的上皮癌:安全性和药物动力学。

癌症。2017年10月1日,123 (19):3843 - 3854。doi: 10.1002 / cncr.30789。2017年5月30日Epub。

PubMed ID

28558150 (在PubMed

]

文摘

背景:Sacituzumab govitecan(方面- 132),一个antitrophoblastic细胞表面抗原(anti-Trop-2)人性化antibody-SN-38共轭,鼓励功效1期临床试验。这份报告进一步检查多个周期的药物动力学和安全方面- 132剂量的8或10毫克/公斤多样化的高级上皮肿瘤患者。方法:患者多个方面- 132天之前治疗收到1和8 21天治疗周期。Trop-2染色存档肿瘤标本,间隙方面- 132及其成分(即免疫球蛋白G(免疫球蛋白),SN-38(伊立替康的喜树碱的活性成分),和glucuronidated SN-38 [SN-38G]),抗体反应,尿苷二磷酸glucuronosyltransferase 1 a1 (UGT1A1)水平测定。安全评估是根据常见的不良事件的术语标准4.0版,和响应进行评估在实体肿瘤中使用响应评估标准,1.1版。结果:不同的转移性癌症患者接受方面- 132 8毫克/公斤(n = 81)和10毫克/公斤(n = 97)。Trop-2是积极的在93%的可用的标本。方面- 132清除半衰期约为11到14个小时,反映从共轭SN-38的释放;免疫球蛋白清除更慢(半衰期,大约103 - 114小时)。大多数SN-38血清(> 95%)的免疫球蛋白。 SN-38G concentrations were lower than SN-38 concentrations. Dose-limiting neutropenia after the first cycle was not correlated with SN-38 in serum or with UGT1A1 genotype. No antibody responses were detected. Objective responses were observed in several indications, including metastatic triple-negative breast cancer, confirming that 10 mg/kg produced an encouraging overall response. CONCLUSIONS: Sacituzumab govitecan has a predictable pharmacokinetic profile and manageable toxicity at doses of 8 and 10 mg/kg. With objective responses and a good therapeutic index at 10 mg/kg, this dose was chosen for future development. Cancer 2017;123:3843-3854. (c) 2017 American Cancer Society.

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药物

Sacituzumab govitecan