博坦西利马布加巴尔斯蒂利马布在复发性/耐火性微卫星稳定转移性结直肠癌中:一阶段1试验
Andrea J Bullock1, Benjamin L Schlechter2, Marwan G Fakih3
1Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nature medicine
|June 13, 2024
概括
博坦西利马布 (BOT) 加巴尔斯蒂利马布 (BAL) 对微卫星稳定转移性结肠直肠癌 (MSS mCRC) 是有前途的,而此前该群体对免疫疗法没有反应. 这种组合疗法在重度预先治疗的患者中显示出令人鼓舞的临床活性和可管理的安全性.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 结肠直肠癌研究研究
背景情况:
- 微卫星稳定转移性结直肠癌 (MSS mCRC) 对传统的免疫检查点阻塞疗法反应不佳.
- 博坦西利马布 (BOT) 是一种Fc增强的抗CTLA-4抗体,旨在增强MSS mCRC等免疫性较差的瘤的免疫反应.
- 作为一种抗PD-1抗体的巴尔斯蒂利马布 (BAL) 正在与BOT.一起进行研究.
研究的目的:
- 评估森利马布 (BOT) 加巴尔斯利马布 (BAL) 的安全性,耐受性和临床活性,在患有MSS的mCRC.患者中.
- 评估客观反应率 (ORR),疾病控制率 (DCR),反应持续时间 (DOR) 和无进展生存率 (PFS).
主要方法:
- 一项正在进行的扩展第一阶段研究包括148名重度预治疗的MSS mCRC患者,接受BOT和BAL.
- 安全性和耐受性是主要终点,在剂量升级和剂量扩展队列中进行评估.
- 二级终点包括RECIST v1.1评估的ORR,DCR,DOR和PFS在101名响应可评估的患者中,随访至少6个月.
主要成果:
- 与治疗相关的不良事件 (TRAEs) 发生在89%的患者中,最常见的是疲劳,腹和炎症;没有报告5级TRAEs.
- 在响应可评估人群中 (n=101),ORR为17% (95%CI,10-26%),DCR为61% (95%CI,51-71%).
- 中位数DOR没有达到,中位数PFS为3.5个月,中位数随访时间为10.3个月.
结论:
- BOT和BAL的组合显示出可管理的安全概况,在MSS mCRC患者中没有新的免疫介导安全信号.
- 观察到令人鼓舞的临床活性和持久的反应,这表明这种免疫疗法组合在以前难以治疗的人群中具有潜力.
- 该临床试验 (NCT03860272) 的数据正在进一步成熟.
相关概念视频
01:15Drugs that Stabilize Microtubules
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
02:56Treatment Resistent Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...