一项随机双盲试验：用TQB2450联合或不联合安罗替尼治疗经过预处理的EGFR/ALK阴性非小细胞肺癌。
A randomized double-blind trial of TQB2450 with or without anlotinib in pretreated driver-negative non-small cell lung cancer.
发表日期：2023 Aug 21
作者：
Wei Zhang, Jing Wang, Qiming Wang, Ying Cheng, Lei Yang, Yuechuan Li, Hua Zhong, Tianqing Chu, Yu Dong, Yanwei Zhang, Fangfei Qian, Liwen Xiong, Chunlei Shi, Cuicui Zhang, Zhen He, Jing Zhu, Xiting Liu, Hui Ma, Kai Li, Baohui Han
来源：
LUNG CANCER
摘要：
免疫单药治疗作为NSCLC非突变驱动基因患者的二线治疗，仅能带来有限的生存效益，因此需要采用联合治疗策略。本期IB期试验研究了抗PD-L1抗体TQB2450与抗血管生成药anlotinib治疗NSCLC的疗效和安全性。研究将预治疗的ⅡB期或Ⅳ期NSCLC患者，EGFR/ALK基因野生型，至少出现一个可测量病变的患者随机分为1:1:1，分别接受TQB2450 1200mg加安慰剂，或TQB2450 1200mg加anlotinib 10mg或12mg。主要结果为无进展生存期（PFS），次要结果包括客观缓解率（ORR）。共有33位患者接受TQB2450加安慰剂，34位患者分别接受TQB2450加anlotinib 10mg和12mg。数据截止时，TQB2450加anlotinib组的中位PFS为8.7个月（95% CI 6.1-17.1），TQB2450单药组为2.8个月（95% CI 1.4-4.7）。TQB2450加anlotinib组的ORR为30.9%（95% CI 20.2%-43.3%），TQB2450单药组为3.0%（95% CI 0.1%-15.8%）。对于PD-L1≥1%的患者，TQB2450加anlotinib组的ORR为50.0%（95% CI 33.4%-66.6%），TQB2450加安慰剂组为5.3%（95% CI 0.1%-26.0%）。没有观察到新的安全信号。TQB2450加anlotinib在NSCLC EGFR和ALK突变患者中表现出了有希望的抗肿瘤活性，毒副反应总体上是可控的。研究结果支持继续开发TQB2450加anlotinib用于NSCLC无驱动基因突变的晚期患者。© 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC.Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg. The primary outcome was progression-free survival (PFS) and the secondary outcomes included objective response rate (ORR).Thirty-three patients received TQB2450 plus placebo and 34 patients each received TQB2450 plus anlotinib 10 mg and 12 mg. At the data cutoff, the median PFS was 8.7 months (95% CI 6.1-17.1) in the TQB2450 plus anlotinib group and 2.8 months (95% CI 1.4-4.7) in the TQB2450 only group. The ORR reached 30.9% (95% CI 20.2%-43.3%) in the TQB2450 plus anlotinib group and was 3.0% (95% CI 0.1%-15.8%) in the TQB2450 only group. In patients with PD-L1 ≥ 1%, the ORR was 50.0% (95% CI 33.4%-66.6%) for TQB2450 plus anlotinib and 5.3% (95% CI 0.1%-26.0%) for TQB2450 plus placebo. No new safety signals were observed.Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. The study findings support the continued development of TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.