AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial

作者：Yuanyuan Zhao, Gang Chen, Jianhua Chen, Li Zhuang, Yingying Du, Qitao Yu, Wu Zhuang, Yanqiu Zhao, Ming Zhou, Weidong Zhang, Yu Zhang, Yixin Wan, Wenting Li, Weifeng Song, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Yunpeng Yang, Wenfeng Fang, Yan Huang, Li Zhang · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.102106 · 被引用次数：104 · 研究领域：Peptidase Inhibition and Analysis、Monoclonal and Polyclonal Antibodies Research、Angiogenesis and VEGF in Cancer

Background Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods This open-label, multicenter, phase II clinical trial was conducted in 11 hospitals in China. Eligible participants were adults aged 18–75 years with locally advanced or metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, and an estimated life expectancy of at least 3 months. The participants were categorized into three cohorts based on prior therapy and functional genomic alterations. Patients in cohort 1 were previously untreated advanced NSCLC, had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene modifications, and received AK112 combined with pemetrexed (500 mg/m 2 ) for non-squamous (non-sq)-NSCLC or paclitaxel (175 mg/m 2 ) for sq-NSCLC plus carboplatin (area under the curve of 5 mg/mL per min) for four cycles, followed by AK112 with pemetrexed for non-sq-NSCLC and AK112 alone for sq-NSCLC as maintenance therapy. The participants in cohort 2 had advanced NSCLC with EGFR-sensitive mutations, failed previous EGFR-tyrosine kinase inhibitor (TKI) ther...