PDF(Pubmed)
Abstract：
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 .
摘要：
针对免疫检查点分子PD-1，PD-L1和CTLA-4的抗体，单独或与化疗联合给药，是大多数转移性非小细胞肺癌患者的治疗标准。当在治愈性手术前给予时，实现了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和可耐受。在一个持续的,开放标签第二阶段研究，60个未选择的生物标志物，未接受治疗的可切除的非小细胞肺癌患者被随机分配接受两种术前剂量的纳武单抗(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，所有患者都遇到了。95％的患者获得了治愈性切除。次要终点包括病理和影像学反应率，病理完全切除率，无病生存率和总体生存率，和安全。27％和10％（nivolumab）以及30％和27％（nivolumab和relatlimab）的患者获得了主要病理（≤10％的活肿瘤细胞）和客观的影像学反应。分别。在100％（nivolumab）和90％（nivolumab和relatlimab）的患者中，经病理完全切除肿瘤和淋巴结。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，每个研究小组有10％和13％的患者报告了≥3级治疗引起的不良事件。探索性分析提供了对术前免疫疗法触发的生物过程的见解。本研究确立了肺癌术前双重靶向PD-1和LAG-3的可行性和安全性。ClinicalTrials.gov识别员：NCT04205552。
