首次对ICOS激动剂费拉迪利马布 (feladilimab) 在患有晚期固体瘤的患者进行人体第一阶段研究
Michele Maio1,2, Victor Moreno3, Juan Martin-Liberal4
1University of Siena, Siena, Italy.
Journal for immunotherapy of cancer
|August 11, 2025
概括
在首次对人类进行的研究中,ICOS激动剂费拉迪利马布 (feladilimab) 显示出可管理的安全性. 确定了0.3和1.0毫克/公斤的推剂量,用于进一步的临床探索.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 临床试验 临床试验
背景情况:
- 诱导性成本刺激器 (ICOS) 受体对于T细胞激活和抗瘤反应至关重要.
- ICOS表达在激活的CD4+和CD8+T细胞上升调节,增强免疫反应.
研究的目的:
- 在首次对人类进行的研究中,评估ICOS激动剂费拉迪利马布的安全性,耐受性和药理动力学.
- 确定用于进一步临床研究费拉迪利马布单一治疗的推剂量.
主要方法:
- 进行了一项剂量升级研究,涉及两个队列 (25 和 67 名参与者).
- 进行了药理动力学/药理动力学 (PK/PD) 分析,以评估药物行为和受体占用率.
- 采用了经过修改的毒性比例间隔设计.
主要成果:
- 费拉迪利马布在广泛的剂量范围 (0.001至10毫克/千克) 中进行了评估,没有确定最大耐受剂量 (MTD).
- 副作用是可以管理的,疲劳,发烧和贫血是最常见的.
- 观察到线性剂量比例和预期的单克隆抗体积累;最佳ICOS受体占用发生在剂量>0.1 mg/kg时.
结论:
- 该研究成功地利用了PK/PD分析和修改的毒性比例间隔设计来确定推剂量.
- 费拉迪利马布具有可容忍和可管理的安全概况,支持其进一步发展.
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