安罗替尼联合派安普利单抗二线治疗 ES-SCLC 的疗效及生物标志物探索：Ⅱ期 ALTER-L041 试验结果

Efficacy and biomarker exploration of anlotinib plus penpulimab in second-line ES-SCLC: Results from the phase 2 ALTER-L041 trial.

期刊: Cell
PMID: 42486095
原文: PubMed ↗
发布日期: 2026-07-23

作者

Liang Zeng — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Fang Tian — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; College of Clinical Medicine, Qinghai University, Xining 810000, China.
Cunji Wang — Department of Oncology, Hunan Provincial Hospital of Traditional Chinese Medicine, Zhuzhou 410013, China.
Qun Chen — Oncology Department, Fuzhou Pulmonary Hospital, Fuzhou 350008, China.
Wenjuan Jiang — Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Juan Liang — Oncology Department, Yiyang Central Hospital, Yiyang 413099, China.
Yanming Tan — GenePlus-Shenzhen, Shenzhen 518000, China.
Huan Yan — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; College of Clinical Medicine, Qinghai University, Xining 810000, China.
Jiao Huang — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; College of Clinical Medicine, Qinghai University, Xining 810000, China.
Chunhua Zhou — Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Haiyan Yang — Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Zhaohui Ruan — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Third Xiangya Hospital, Central South University, Changsha 410000, China.
Zhe Huang — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Department of Pathology, School of Basic Medical Science, Central South University, Changsha 410013, China.
Jiacheng Dai — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Yuanqing Feng — Oncology Department, Xiangtan Central Hospital, Xiangtan 4111002, China.
Yi Xiong — Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Li Liu — Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Chengzhi Zhou — Respiratory Zone Five / Oncology Center Zone One, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China.
Qinqin Xu — Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining 810000, China.
Yue Xie — GenePlus-Shenzhen, Shenzhen 518000, China.
Chao Zhang — GenePlus-Shenzhen, Shenzhen 518000, China.
Haoran Guo — Central Medical Center,Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing 211100, China.
Bing Zhang — Oncology Department, Yiyang Central Hospital, Yiyang 413099, China. Electronic address: 2558042026@qq.com.
Zhijun Wu — Oncology Department, The First People's Hospital of Changde City, Changde 417500, China. Electronic address: 1056068115@qq.com.
Nong Yang — Department of Medical Oncology, Hunan Second People's Hospital, Changsha 410013, China. Electronic address: yangnong0217@163.com.
Yongchang Zhang — Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China. Electronic address: zhangyongchang@csu.edu.cn.

作者单位

Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; College of Clinical Medicine, Qinghai University, Xining 810000, China.
Department of Oncology, Hunan Provincial Hospital of Traditional Chinese Medicine, Zhuzhou 410013, China.
Oncology Department, Fuzhou Pulmonary Hospital, Fuzhou 350008, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Oncology Department, Yiyang Central Hospital, Yiyang 413099, China.
GenePlus-Shenzhen, Shenzhen 518000, China.
Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Third Xiangya Hospital, Central South University, Changsha 410000, China.
Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Department of Pathology, School of Basic Medical Science, Central South University, Changsha 410013, China.
Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Oncology Department, Xiangtan Central Hospital, Xiangtan 4111002, China.
Respiratory Zone Five / Oncology Center Zone One, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China.
Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining 810000, China.
Central Medical Center,Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing 211100, China.
Oncology Department, Yiyang Central Hospital, Yiyang 413099, China. Electronic address: 2558042026@qq.com.
Oncology Department, The First People's Hospital of Changde City, Changde 417500, China. Electronic address: 1056068115@qq.com.
Department of Medical Oncology, Hunan Second People's Hospital, Changsha 410013, China. Electronic address: yangnong0217@163.com.
Early Clinical Trial Center, Office of National Drug Clinical Trial Institution, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China; Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China. Electronic address: zhangyongchang@csu.edu.cn.

摘要

中文

广泛期小细胞肺癌（ES-SCLC）患者在一线含铂化疗失败后治疗选择有限。本项开放标签、单臂、多中心 Ⅱ 期试验评估了派安普利单抗联合安罗替尼治疗 65 例一线铂类耐药 ES-SCLC 患者的疗效。经盲态独立中心评审确认的客观缓解率为 41.5%（95% CI：29.2%-53.8%），疾病控制率为 75.4%（95% CI：64.6%-86.1%）。中位无进展生存期和总生存期分别为 4.4（95% CI：3.5-5.3）个月和 10.5（95% CI：4.1-17.2）个月。23.1% 的患者发生 ≥3 级治疗相关不良事件，未出现新的安全信号。探索性循环肿瘤 DNA（ctDNA）分析提示，较低的基线最大体细胞等位基因频率与生存改善相关，并在疾病进展时观察到 T 细胞受体克隆多样性降低。派安普利单抗联合安罗替尼显示出良好的抗肿瘤活性和可控的安全性，可能成为铂类耐药 ES-SCLC 的潜在二线治疗方案。本研究已在 ClinicalTrials.gov 注册（NCT05001971）。

English

Treatment options are limited for patients with extensive-stage small cell lung cancer (ES-SCLC) after platinum-based therapy. This open-label, single-arm, multicenter phase 2 trial evaluates penpulimab plus anlotinib in 65 patients with first-line platinum-resistant ES-SCLC. The confirmed objective response rate by blinded independent central review is 41.5% (95% confidence interval [CI]: 29.2%-53.8%), and the disease control rate is 75.4% (95% CI: 64.6%-86.1%). Median progression-free survival and overall survival are 4.4 (95% CI: 3.5-5.3) and 10.5 (95% CI: 4.1-17.2) months, respectively. Grade ≥3 treatment-related adverse events occurred in 23.1% of patients, with no new safety signals. Exploratory circulating tumor DNA (ctDNA) analysis suggests that lower baseline maximum somatic allele frequency is associated with improved survival, and decreased T cell receptor clonal diversity is observed at disease progression. Penpulimab plus anlotinib shows promising antitumor activity with a manageable safety profile and may represent a potential second-line treatment option for platinum-resistant ES-SCLC. This study was registered at ClinicalTrials.gov (NCT05001971).

分类与指标

研究类型: 临床研究
病种: 肺癌
JCR 分区: Q1
影响因子: 45.1
新锐分区: 1区