A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC

作者：Lei Wang, Yongzhong Luo, Shengxiang Ren, Zhihong Zhang, Anwen Xiong, Chunxia Su, Jin Zhou, Xinmin Yu, Yanping Hu, Xiaodong Zhang, Xiaorong Dong, Shuyan Meng, Fengying Wu, Xiaoming Hou, Yuanrong Dai, Weifeng Song, Baiyong Li, Zhongmin Maxwell Wang, Xia Yu, Caicun Zhou · 发表于：Journal of Thoracic Oncology · 年份：2023 · DOI：10.1016/j.jtho.2023.10.014 · 被引用次数：64 · 研究领域：Angiogenesis and VEGF in Cancer、Monoclonal and Polyclonal Antibodies Research、PARP inhibition in cancer therapy

INTRODUCTION: This study (HARMONi-5) aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor) as first- or second-line monotherapy in patients with advanced immunotherapy-naive NSCLC. METHODS: Eligible patients received intravenous ivonescimab 10 mg/kg every 3 weeks (Q3W), 20 mg/kg every 2 weeks (Q2W), 20 mg/kg Q3W, or 30 mg/kg Q3W. The primary end points were safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: At data cutoff (October 5, 2022), 108 patients were enrolled and received ivonescimab. Programmed death ligand-1 tumor proportion score (TPS) was greater than or equal to 1% in 74 patients (68.5%), including 35 (32.4%) with TPS greater than or equal to 50%. The median follow-up was 10.4 months (range: 8.4-10.9 mo). For all patients, ORR and disease control rate were 39.8% and 86.1%, respectively. ORR by TPS was 14.7%, 51.4%, and 57.1% in patients with TPS less than 1%, greater than or equal to 1%, and greater than or equal to 50%, respectively. In the 67 programmed death ligand-1-positive patients receiving first-line ivonescimab, the ORR was 33.3%, 52.6%, 60.0%, and 75.0% at the doses of 10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W, and 30 mg/kg Q3W, respectively. Grade greater than or equal to 3 treatment-related adverse events (TRAEs) were observed in 24 patients (22.2%). TRAEs leading to treatment discontinua...