中国临床药理学杂志2017，Vol.33Issue(17)：1725-1727,3.DOI:10.13699/j.cnki.1001-6821.2017.17.032
肿瘤治疗抗体偶联药物首次临床试验起始剂量的拟定
Considerations on the dose selection for first-in-human clinical trials with antibody drug conjugates for oncology
闫莉萍 1王庆利 1王海学1
作者信息
- 1. 国家食品药品监督管理总局药品审评中心,北京100038
- 折叠
摘要
Abstract
Antibody drug conjugates (ADCs) as anti-cancer agents are designed to improve the therapeutic index of the cytotoxin by specifically delivering cytotoxin to tumor cells.The development path for ADCs is more complex and challenging than for unmodified antibodies orcytotoxin.One challenge is the selection of the first-in-human (FIH) dose in the development process from the preclinical stage to the subsequent clinical phase.This paper reviews the nonclinical safety studies supporting the first-in-human clinical trials and discusses the appropriate approaches for the selection of first-in-human dose.FIH doses that is 1/6th the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys or 1/10th the STD10 in rodents scaled according to body surface area (BSA) and 1/10th the NOAEL in monkeys or rodents using body weight for scaling generally are relatively safe.关键词
抗体偶联药物/肿瘤治疗/非临床安全性研究/首次临床试验起始剂量Key words
antibody drug conjugate/oncology/nonclinical safety study/first-in-human dose分类
医药卫生引用本文复制引用
闫莉萍,王庆利,王海学..肿瘤治疗抗体偶联药物首次临床试验起始剂量的拟定[J].中国临床药理学杂志,2017,33(17):1725-1727,3.
