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

作者：Liang Zeng, Fang Tian, C Wang, Qun Chen, Wenjuan Jiang, Juan Liang, Yanming Tan, Huan Yan, Jiao Huang, Chunhua Zhou, Haiyan Yang, Zhaohui Ruan, Zhe Huang, Jiacheng Dai, Yuanqing Feng, 熊艺, Li Liu, Chengzhi Zhou, Qinqin Xu, Yue Xie, Chao Zhang, Haoran Guo, Bing Zhang, Zhijun Wu, Nong Yang, Yongchang Zhang · 发表于：Cell Reports Medicine · 年份：2026 · DOI：10.1016/j.xcrm.2026.102931 · 研究领域：Lung Cancer Research Studies、PARP inhibition in cancer therapy、Cancer therapeutics and mechanisms

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).