本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02965-0

摘要内容如下：

针对免疫检查点分子PD-1、PD-L1和CTLA-4的抗体，单独给药或与化疗联合给药，是大多数转移性非小细胞肺癌患者的标准治疗方案。当在根治性手术前给药时，可获得肿瘤反应和改善的无事件生存率。新的抗体组合可能更有效且更可耐受。在一项正在进行的开放标签2期研究中，60名未选择生物标志物、未经治疗的可切除非小细胞肺癌患者随机接受两种术前剂量的nivolumab（抗PD-1）联合或不联合relatlimab（抗LAG-3）抗体治疗。主要研究终点是43天内手术的可行性，所有患者均符合。95%的患者获得了根治性切除。次要终点包括病理和影像学缓解率、病理完全切除率、无病生存率和总生存率以及安全性。27%和10%（Nivolumab）以及30%和27%（Nivolumab和Relatlimab）的患者分别获得主要病理（≤10%活肿瘤细胞）和客观放射学反应。在100%（Nivolumab）和90%（Nivolumab和Relatlimab）的患者中，肿瘤和淋巴结在病理上被完全切除。中位随访时间为12个月，12个月的无病生存率和总生存率分别为89%和93%（Nivolumab），93%和100%（Nivolumab和Relatlimab）。两种治疗都是安全的，每个研究组分别有10%和13%的患者报告了≥3级的治疗中出现的不良事件。探索性分析为术前免疫治疗引发的生物学过程提供了见解。本研究确立了肺癌手术前PD-1和LAG-3双重靶向的可行性和安全性。ClinicalTrials.gov标识符：NCT04205552。

英文原文如下：

Abstracts

Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552 .

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