在NTRK融合阳性先进固体瘤中使用Repotrectinib:一个1/2阶段试验
Benjamin Besse1, Jessica J Lin2, Lyudmila Bazhenova3
1Paris-Saclay University, Gustave Roussy Cancer Center, Villejuif, France. Benjamin.BESSE@gustaveroussy.fr.
Nature medicine
|February 4, 2026
概括
新一代氨酸激酶抑制剂 (TKI) Repotrectinib在NTRK融合阳性固体瘤中显示出持久的反应. 这种TKI即使在先前用TKI治疗的患者和具有特定突变的患者中也有效,显示出有利的安全性.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 遗传学 是一个遗传学.
背景情况:
- 早期一代TRK氨酸激酶抑制剂 (TKI) 对NTRK融合阳性 (NTRK+) 固体瘤提供临床益处,但受到新兴耐药性的限制.
- 雷波特雷克提尼布是一种下一代ROS1/TRK TKI,设计具有宏循环结构,以增强反应耐用性.
研究的目的:
- 评估repotrectinib在患有晚期固体瘤的成年患者中的疗效和安全性,特别关注NTRK+疾病.
- 评估repotrectinib在TKI-naive和TKI-pretreated患者群体中的性能,包括具有特定NTRK溶剂前端突变的患者.
主要方法:
- 在TRIDENT-1试验 (第1/2期,NCT03093116) 中,对患有晚期固体瘤,包括NTRK+疾病的患者进行了评估.
- 主要终点:确认的客观反应率. 二级终点:反应持续时间 (DOR),无进展生存率 (PFS),整体生存率和安全性.
- 患者被分为TKI-naive和TKI-pretreated队列,分组分析溶剂前端突变和内疾病.
主要成果:
- 在TKI原始患者 (n=51) 中,应答率为59% (95%CI:44-72),中位数PFS为30.3个月 (9.0-NE).
- 在TKI预治疗患者 (n=69) 中,应答率为48% (95% CI:36-60) ,中位数DOR为9.8个月 (7.4-13.0) 和中位数PFS为7.4个月 (3.9-9.7).
- 在30名具有NTRK溶剂前端突变的TKI预治疗患者中,有16名反应 (53%;95%CI:34-72). 在两个队列中都观察到内反应.
结论:
- 在NTRK+固体瘤患者中,包括先前接受TRK TKI治疗和溶剂前端突变的患者中,Repotrectinib表现出持久的全身和内反应.
- 与治疗相关的不良事件通常是低级的, discontinuation率低 (4%),支持repotrectinib的良好的安全性.
- 这些发现支持repotrectinib作为诊断为NTRK融合阳性固体瘤的患者的有价值的治疗选择.
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