临床和转化研究ivosidenib加nivolumab在先进的固体瘤中,这些瘤含有IDH1突变
Matthew K Nguyen1,2,3, Mark Jelinek1,4, Arjun Singh1,5
1UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
The oncologist
|October 25, 2025
概括
伊沃西迪尼布加尼沃卢马布在患有突变IDH1固体瘤的患者中显示出有限的临床益处. 然而,IDH1抑制可能会改变瘤免疫相互作用,这表明未来免疫疗法组合的潜力.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 代谢重编程 代谢重编程
背景情况:
- 对免疫治疗没有反应的癌症通常具有非T细胞炎症瘤微环境 (TME).
- 突变IDH1 (mIDH1) 富含这种TME表型,并通过代谢重编程驱动免疫排除.
- 临床前数据表明,IDH抑制可以恢复抗瘤免疫力.
研究的目的:
- 评估ivosidenib (一种IDH1抑制剂) 与nivolumab (一种抗PD1抗体) 结合的初步活性.
- 为了评估mIDH1高级固体瘤患者的安全性和疗效.
主要方法:
- 一项II期研究招募了患有晚期或耐火性mIDH1固体瘤的患者.
- 艾沃西迪尼布 (每天500毫克) 和尼沃卢马布 (每4周服用480毫克) 进行了治疗.
- 主要终点:六个月无进展生存率 (PFS6) 或整体应答率 (ORR). 翻译分析包括药理动力学,蛋白质组学和空间转录组学.
主要成果:
- 招募了15名患者,20%的患者达到主要终点 (PFS6或ORR).
- 中位数PFS为1.94个月.
- 治疗减少了血 (R) - 2HG,在经历临床益处的患者中减少更大. 探索性分析表明免疫调节效应.
结论:
- 伊沃西迪尼布加尼沃卢马布在这个患者组中显示出安全性,但临床益处有限.
- 翻译数据表明,IDH1抑制可以调节瘤与免疫相互作用.
- 这些发现为未来结合IDH1抑制剂与免疫检查点抑制剂的研究提供了基础.
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