尼沃卢马布与干扰素 - 玛联合用于晚期固体瘤患者的第一阶段研究
Matthew Zibelman1, Alexander W MacFarlane2, Kimberly Costello3
1Department of Hematology Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. matthew.zibelman@fccc.edu.
Nature communications
|July 27, 2023
概括
这项试验将干扰素- (IFN-γ) 与尼沃卢马布结合用于转移性固体瘤. 该组合显示出良好的安全性,第二阶段推剂量为50mcg/m2 IFN-γ.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 临床试验 临床试验
背景情况:
- 转移性固体瘤仍然是一个重大的临床挑战.
- 像尼沃卢马布这样的免疫检查点抑制剂已经彻底改变了癌症治疗.
- 结合免疫疗法可能会增强抗瘤反应.
研究的目的:
- 为了评估安全性并确定将干扰素- (IFN-γ) 与nivolumab结合的推第二阶段剂量 (RP2D).
- 评估剂量限制性毒性 (DLT) 和与免疫相关的不良事件 (irAEs).
- 探索初步的疗效和相关的生物标志物.
主要方法:
- 一期,对26名转移性实体瘤患者进行剂量升级研究.
- 四个剂量队列评估了IFN-γ的增加剂量与固定的尼沃卢马布剂量.
- 安全性,DLT,IRE和RP2D是主要的终点. 研究了有效性和相关标志物.
主要成果:
- IFN-γ的最大耐受剂量为75mcg/m2,RP2D被确定为50mcg/m2.
- 大多数不良事件都是低级的,与IFN-γ相关. 只有一个患者出现了任何irrAEs,没有观察到3级irrAEs.
- 探索性疗效显示了一个完整的反应和五例稳定的疾病. 单细胞上增加的PD-L1表达与IFN-γ剂量相关.
结论:
- 在患有转移性固体瘤的患者中,IFN-γ和nivolumab的组合是安全的和可以容忍的.
- 推的第二阶段IFN-γ剂量是50mcg/m2与尼沃卢马布结合时.
- IFN-γ可能通过免疫细胞调节和化学诱导来增强抗瘤免疫力,可能减少irAEs.
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