在患有复发性或耐药性血液性恶性瘤的患者中进行罗格塞基布的第一阶段研究
Hisayuki Yokoyama1, Noriko Fukuhara2, Koji Ando3
1Department of Hematology and Cell Therapy, Yamagata University Hospital, Yamagata, Japan.
Blood advances
|October 7, 2025
概括
作为一种新型RNA拼接抑制剂的Rogocekib在治疗复发性急性髓性白血病和骨髓失质综合征方面表现有前途. 早期的第一阶段试验表明可管理的安全性和初步疗效,需要进一步调查.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 罗格塞基布是第一类,口服可用的CDC2类激酶抑制剂,向RNA剪接.
- 临床前研究表明,罗格塞基布在血液性恶性瘤中具有抗增殖作用.
- 一项第一阶段研究评估了罗格塞基布在复发性/耐药性急性髓性白血病 (AML) 和更高风险的骨髓发育综合征 (MDS) 的治疗.
研究的目的:
- 评估罗格塞基布在复发或耐药AML和高风险MDS患者的安全性和初步疗效.
- 为了确定罗格塞基布的剂量限制性毒性和药理动力学/药理动力学特征.
主要方法:
- 一个第1,3+3期剂量升级研究,使用罗格塞基布囊每周两次服用70毫克或105毫克.
- 通过不良事件来评估安全性;通过完全缓解率 (CR) 来评估有效性.
- 进行了药理动力学 (PK) 和药理动力学 (PD) 分析.
主要成果:
- 一种剂量限制性毒性 (第四级肺炎) 发生在每周两次服用105毫克时.
- 在AML患者 (n=12) 中,CR为25.0%,非完全血液恢复的CR为8.3%.
- 在MDS患者 (n=2) 中,CR为50.0%. 较高的罗格塞基布暴露与增加的外跳跃相关.
结论:
- 罗戈塞基布在患有复发/耐药AML和高风险MDS的患者中显示出可管理的安全性和初步疗效.
- 在正在进行的1/2期研究中需要进一步调查.
- 罗格塞基布的作用机制涉及调节RNA剪接,这是外因子跳跃在外周血细胞的证据.
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