从I-III期研究中发现的Copanlisib群体药理动力学和与rituximab结合的暴露-反应关系
Peter N Morcos1, Jonathan Moss2, Rupert Austin2
1Bayer HealthCare Pharmaceuticals, Inc., Whippany, New Jersey, USA.
CPT: pharmacometrics & systems pharmacology
|June 30, 2023
概括
评估了在不强烈的非霍奇金淋巴瘤 (iNHL) 治疗中与rituximab结合使用copanlisib的剂量. 目前的60mg剂量方案支持疗效和耐受性,较低剂量没有明显的安全益处.
科学领域:
- 药理学和瘤学 药理学和瘤学
- 临床试验分析
背景情况:
- 利西布的剂量选择是基于最大耐受剂量,而不是与rituximab的特定组合研究.
- 在CHRONOS-3试验中,在复发性无痛非霍奇金淋巴瘤 (iNHL) 中,使用copanlisib加Rituximab可以改善无进展生存率.
研究的目的:
- 对INHL患者的疗效和安全性进行调查,调查利西布的群体药理动力学 (PopPK) 和暴露-反应 (ER) 关系.
- 评估共变量对利西布药理动学的影响,并确定最佳的剂量策略.
主要方法:
- 针对PopPK的9个I-III期Copanlisib研究中的712名患者的综合分析.
- 使用CHRONOS-3试验1年随访数据进行暴露-反应分析.
- 多变量回归模型来评估ER与基线共变量之间的关系.
主要成果:
- 科潘利西布的药理动力学最好用三部分模型来描述;确定的共同变量具有适度的影响.
- 在CHRONOS-3中观察到时间变化的copanlisib暴露和无进展生存率之间存在显著的关系.
- 没有发现显著的暴露与安全关系,这表明较低的剂量可能会降低疗效,而不会改善耐受性.
结论:
- 目前的间歇性用量疗法 (60mg在第1,8,15天) 是由PopPK和ER数据支持的.
- 这种剂量支持了在INHL治疗中与rituximab联合使用的copanlisib观察到的临床疗效.
- 没有证据表明更低的剂量会提高这种组合治疗的安全性或耐受性.
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