在固体瘤中使用OMO-103准MYC:一阶段1试验
Elena Garralda1, Marie-Eve Beaulieu2, Víctor Moreno3
1Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Nature medicine
|February 6, 2024
概括
一项第一阶段研究评估了OMO-103,一种新型MYC抑制剂,用于高级固体瘤. 该药物表现出良好的安全性和抗瘤活性初步迹象,确定了推的第二阶段剂量.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物开发 药物开发
背景情况:
- 瘤基因MYC是癌症治疗中的关键标,但被认为是无法治疗的.
- OMO-103是一种新的小蛋白抑制剂,向MYC.
研究的目的:
- 评估OMO-103在患有晚期固体瘤的患者的安全性和耐受性.
- 确定推的第二阶段剂量 (RP2D),并评估抗瘤活性和药理动学的初步迹象.
主要方法:
- 一个第1期,开放标签,剂量升级研究,使用3+3设计,每周静脉注射OMO-103.
- 招募了22名患有晚期固体瘤的患者,治疗直到进展,并评估了安全性,药理动力学和活性.
- 转录组分析和可溶性因子识别用于目标参与和响应标志物评估.
主要成果:
- 一般来说,OMO-103的耐受性很好,最常见的不良事件是1级输液相关反应.
- 在剂量水平5 (DL5) 观察到一种剂量限制性毒性.
- 药理动力学显示非线性,在DL5时有组织和迹象;在19名可评估患者中,有8名患者患有稳定的疾病,其中一名患者显示瘤体积减少了49%.
结论:
- OMO-103是一种安全且耐受的MYC抑制剂,在先进的固体瘤中具有临床活性的早期迹象.
- 推的第二阶段剂量被确定为DL5 (6.48 mg/kg).
- 需要在第二阶段试验中进行进一步的研究,以确认疗效并确定可预测的生物标志物.
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