在耐火固体瘤患者中与olapararib结合使用adapvosertib:一项开放式标签,剂量确定和剂量扩展的Ib期试验
Erika P Hamilton1, Gerald S Falchook2, Judy S Wang3,4
1Sarah Cannon Research Institute, 250 25th Avenue North, Nashville, TN, 37203, USA. Erika.Hamilton@scri.com.
Targeted oncology
|November 2, 2024
概括
这项研究评估了对耐火实体瘤患者的阿达沃谢蒂布加奥拉帕里布. 该组合显示了可控的安全性,但有限的抗瘤活性,定义了用于进一步试验的推剂量.
科学领域:
- 在瘤学瘤学.
- 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:
- 阿达沃谢蒂布是一种选择性的Wee1抑制剂;奥拉巴里布是一种PARP抑制剂.
- 临床前研究表明,阿达沃谢蒂布可以增强PARP抑制剂的疗效.
- 这项研究研究了在固体瘤中对阿达沃谢蒂布和奥拉帕里布的组合.
研究的目的:
- 为了评估阿达沃谢蒂布加奥拉帕里布的安全性,耐受性和疗效.
- 确定组合治疗的最大耐受剂量 (MTD) 和推的II期剂量 (RP2D).
- 评估患有耐火固体瘤的患者的组合,包括小细胞肺癌 (SCLC).
主要方法:
- 进行了一项I/II期临床试验,其中包括剂量发现 (A部分) 和剂量扩展 (B部分) 队列.
- 患者在定义的时间表上接受了阿达沃谢蒂布 (每天一次或两次) 和奥拉巴里布 (每天两次).
- 资格标准包括耐火固体瘤或敏感性/复发性SCLC.
主要成果:
- 确定了MTD和RP2D,用于每天两次和每天一次的阿达沃谢蒂布配合olaparib的剂量表.
- 与治疗相关的常见不良事件包括疲劳,腹,食欲下降,恶心和贫血.
- 在A部分,整体客观响应率 (ORR) 为14.8%. 在SCLC队列中,ORR为11.1%,疾病控制率为22.2%.
结论:
- 副作用和剂量限制性毒性是可以管理的,并且与已知的阿达沃谢蒂布和olaparib的安全性概况一致.
- 组合疗法显示出有限的整体抗瘤活性.
- 成功定义了MTD和RP2D,为未来的临床研究提供了基础.
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