基于模型的药物开发范式应用于用于晚期发展阶段的datopotamab deruxtecan剂量选择
Yasong Lu1, Shuang Liang1, Ying Hong1
1Quantitative Clinical Pharmacology, Daiichi Sankyo, Inc., Basking Ridge, New Jersey, USA.
基于模型的药物开发 (MIDD) 确定6mg/kg为达托帕马布德鲁克斯坦的最佳剂量,比肺癌患者的最大耐受剂量 (MTD) 提供更好的益处风险平衡.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床试验设计 临床试验设计
背景情况:
- 传统的最大耐受剂量 (MTD) 方法用于瘤学的剂量选择正受到基于模型的药物开发 (MIDD) 的挑战.
- 达托帕马布德鲁克斯泰坎 (Dato-DXd) 是一种TROP2定向的抗体-药物合物,正在针对晚期/转移性非小细胞肺癌 (NSCLC) 进行研究.
研究的目的:
- 在I期临床开发中应用MIDD方法来优化剂量和选择达托帕马布德鲁克斯坦.
- 确定达托-DXd的最佳剂量,以平衡晚期发育阶段的疗效和耐受性.
主要方法:
- 使用TROPION-PanTumor01第一阶段研究的数据进行了代人群药理动力学 (PK) 和暴露-反应分析.
- 数据包括每3周服用0.27-10毫克/千克的剂量范围内的Dato-DXd治疗NSCLC患者的PK,疗效和安全性.
主要成果:
- 达托-DXd的6mg/kg剂量被第二个数据切断确定为最佳,并被第三个数据确认.
- 与8mg/kg的MTD相比,6mg/kg的剂量显示出更好的耐受性 (间歇性肺病,口炎,粘膜炎的较低率).
- 与4mg/kg剂量相比,6mg/kg剂量显示出更高的疗效,具有更高的模拟客观反应率 (23.8%vs18.6%) 和更好的无进展生存率.
结论:
- 达托帕马布德鲁克斯泰坎6mg/kg剂量为晚期/转移性NSCLC提供了最佳的益处风险平衡.
- 本案例研究验证了MIDD在瘤药物开发中优化剂量选择的实用性.
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