TQB2450联合或不联合安罗替尼用于局部晚期/不可切除的非小细胞肺癌患者的维持治疗，这些患者在先前同步/序贯放化疗后未进展（R-ALPS）：一项随机、双盲、安慰剂对照、多中心III期试验的研究方案
TQB2450 with or without anlotinib as maintenance treatment in subjects with locally advanced/unresectable non-small cell lung cancer that have not progressed after prior concurrent/sequential chemoradiotherapy (R-ALPS): study protocol for a randomized, double-blind, placebo-controlled, multicenter phase III trial.
作者信息
Dong Baiqiang, Chen Long, Pang Qingsong, Jiang Ou, Ge Hong, Cheng Yufeng, Zhou Rongrong, Meng Xiangjiao, Li Jie, Zhu Xuan, Wang Xunqiang, Cao Qiuyue, Ji Yongling, Chen Ming
机构信息
State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
出版信息
Transl Lung Cancer Res. 2024 Oct 31;13(10):2828-2837. doi: 10.21037/tlcr-24-362. Epub 2024 Oct 28.
BACKGROUND
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). TQB2450 (benmelstobart) is a novel humanized immunoglobulin G1 monoclonal antibody against programmed death-ligand 1 (PD-L1). Anlotinib, an oral multitargeted anti-angiogenic agent with potential synergy with ICIs, has shown efficacy in relapsed and advanced NSCLC. Accumulating preclinical data suggest a synergism between immunological and anti-angiogenic therapies through the improvement of the immune microenvironment of the tumor. In this study, we hypothesized that the combination of TQB2450 and anlotinib as maintenance treatment would enable further improvements in the outcomes of patients with locally advanced/unresectable NSCLC without driver mutations that have not progressed after definitive chemoradiotherapy.
METHODS
The Radiotherapy and Anlotinib Let PD-L1 Superb (R-ALPS) study is a randomized, double-blind, placebo-controlled, multicenter phase III study (Clinicaltrials.gov identifier, NCT04325763). A total of 534 eligible participants will be randomized to receive TQB2450 (1,200 mg) plus anlotinib (8 mg), or TQB2450 (1,200 mg) plus placebo, or placebo as maintenance therapy. Progression-free survival (PFS), assessed by the independent review committee is the primary endpoint. The secondary endpoints include additional measures of efficacy, safety, and biomarkers. An interim analysis of the effectiveness will be conducted when 70% (286 cases) of the total PFS events have been reached.
DISCUSSION
The development of the R-ALPS study will contribute to a deeper insight into the interplay between immunotherapy and anti-angiogenic therapy and thus might expand the treatment options available to patients with locally advanced or unresectable NSCLC.
TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT04325763. Date of registration: May 27, 2020. Protocol version: Version 4.0, Sep 16, 2022 (https://classic.clinicaltrials.gov/ct2/show/NCT04325763).
背景
免疫检查点抑制剂（ICIs）彻底改变了非小细胞肺癌（NSCLC）的治疗方式。TQB2450（苯美司托巴特）是一种新型的抗程序性死亡配体1（PD-L1）人源化免疫球蛋白G1单克隆抗体。安罗替尼是一种口服多靶点抗血管生成药物，与ICIs可能具有协同作用，已在复发和晚期NSCLC中显示出疗效。越来越多的临床前数据表明，免疫治疗和抗血管生成治疗通过改善肿瘤免疫微环境而产生协同作用。在本研究中，我们假设TQB2450与安罗替尼联合作为维持治疗能够进一步改善局部晚期/不可切除且无驱动基因突变、在确定性放化疗后未进展的NSCLC患者的预后。
方法
放疗与安罗替尼使PD-L1更出色（R-ALPS）研究是一项随机、双盲、安慰剂对照、多中心III期研究（Clinicaltrials.gov标识符，NCT04325763）。共有534名符合条件的参与者将被随机分组，接受TQB2450（1200mg）加安罗替尼（8mg），或TQB2450（1200mg）加安慰剂，或安慰剂作为维持治疗。由独立审查委员会评估的无进展生存期（PFS）是主要终点。次要终点包括疗效、安全性和生物标志物的其他测量指标。当达到总PFS事件的70%（286例）时，将进行有效性的中期分析。
讨论
R-ALPS研究的开展将有助于更深入地了解免疫治疗与抗血管生成治疗之间的相互作用，从而可能扩大局部晚期或不可切除NSCLC患者的治疗选择。
试验注册
Clinicaltrials.gov标识符：NCT04325763。注册日期：2020年5月27日。方案版本：版本4.0，2022年9月16日（https://classic.clinicaltrials.gov/ct2/show/NCT04325763）。
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