对于瘤学剂量发现剂量优化有三个步骤
Jason J Z Liao1, Ekaterine Asatiani2, Qingyang Liu1
1Incyte Corporation, 1801 Augustine Cut-off, Wilmington, DE, 19803, United States.
一种新的三步方法提高了瘤药物剂量选择,超出了传统的最大耐受剂量 (MTD) 方法. 这一策略优化了注册试验的剂量,平衡了针对性治疗的安全性和有效性.
科学领域:
- 在瘤学瘤学.
- 临床药理学 临床药理学
- 药物开发 药物开发
背景情况:
- 传统的瘤学剂量选择依赖于最大耐受剂量 (MTD),这可能不适合分子向疗法,因为不同的毒性概况.
- 美国食品和药物管理局的项目Optimus旨在改革瘤药物开发中的剂量优化.
研究的目的:
- 为响应 Project Optimus 项目的倡议,提出并详细说明"向剂量优化迈进的三步"程序.
- 加强瘤学注册试验最佳剂量选择.
主要方法:
- 步骤1:使用高效的混合设计进行剂量升级,以识别MTD或过量控制的最大给药剂量.
- 步骤2:根据安全性,药理动力学,药理动力学和生物标志物数据选择推剂量扩张 (RDE).
- 步骤3:使用随机分数因数设计和多个RDE在瘤队列中的剂量优化.
主要成果:
- 拟议的混合设计提高了MTD识别的准确性.
- 多种数据 (安全性,PK,PD,生物标志物) 的整合为RDE选择提供了信息.
- 分数因数设计允许探索多个剂量和瘤类型,以获得最佳的注册剂量选择.
结论:
- 三步方法增加了选择注册试验最佳剂量的可能性.
- 这种方法旨在实现平衡的安全性,同时保持有效性.
- 它有助于识别对研究治疗最有反应的瘤类型.
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