新辅助药尼沃卢马布和relatlimab在局部晚期的MMR缺乏结肠癌:一个第二阶段试验
Peter G M de Gooyer1, Yara L Verschoor1, Lauren D W van den Dungen1
1Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Nature medicine
|September 15, 2024
概括
新辅助剂尼沃卢马布加上relatlimab在不匹配修复缺陷结肠癌 (dMMR CC) 中显示出高疗效. 这种免疫疗法组合取得了显著的病理反应,需要在更大的临床试验中进一步调查.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 胃肠道癌症 胃肠道癌症
背景情况:
- 不匹配修复缺陷 (dMMR) 发生在约15%的非转移性结肠癌 (CCs) 中,导致过度突变的免疫性瘤.
- dMMR CCs对化疗反应有限,但对新辅助抗PD-1加抗CTLA-4免疫疗法反应良好.
- 之前的黑色素瘤研究表明,抗PD-1加抗LAG-3免疫疗法具有高疗效和有利的毒性.
研究的目的:
- 评估新辅助药尼沃卢马布加上relatlimab在患有局部发达dMMRCC的患者中的疗效和安全性.
- 评估这种患者队列中的病理反应率作为主要终点.
主要方法:
- 在NICHE-3研究中,59名患者接受了局部晚期dMMRCC的治疗.
- 患者在手术前接受了两次每4周一次的尼沃卢马布 (480毫克) 加上relatlimab (480毫克) 循环.
- 术后评估了病理反应,包括主要和完整的反应.
主要成果:
- 97%的患者 (57/59) 取得了病理反应,达到主要终点.
- 在92% (54/59) 的患者中观察到重大病理反应 (≤10%的残留瘤),在68% (40/59) 的患者中观察到完全反应.
- 治疗显示了可接受的安全性,其中10%的患者经历了3-4级免疫相关的不良事件.
结论:
- 新辅助剂尼沃卢马布/雷拉利马布在局部发达的dMMR CC中诱导了高的病理反应率.
- 这种组合显示出有利的安全性概况,观察到的复发率最小.
- 需要在更大的研究中进行进一步的调查,以证实dMMR CC.中新辅助免疫疗法的这些有希望的发现.
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