Wang Lei, Luo Yongzhong, Ren Shengxiang, Zhang Zhihong, Xiong Anwen, Su Chunxia, Zhou Jin, Yu Xinmin, Hu Yanping, Zhang Xiaodong, Dong Xiaorong, Meng Shuyan, Wu Fengying, Hou Xiaoming, Dai Yuanrong, Song Weifeng, Li Baiyong, Wang Zhongmin Maxwell, Xia Yu, Zhou Caicun
Oncology Department, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
The First Department of Thoracic Medicine, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.
J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.
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.
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.
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 discontinuation occurred in one patient (0.9%). TRAEs leading to death occurred in three patients (2.8%) with squamous NSCLC. The occurrence of grade greater than or equal to 3 TRAEs and grade greater than or equal to 3 bleeding events in squamous versus nonsquamous NSCLC patients was 25.5% versus 18.9% and 0.0% versus 1.9%, respectively.
Ivonescimab monotherapy was well tolerated and found to have a promising efficacy in patients with advanced or metastatic NSCLC.
gov identifier: NCT04900363.
本研究（HARMONi-5）旨在评估伊沃西单抗（一种抗程序性细胞死亡蛋白1和血管内皮生长因子的双特异性抗体）作为一线或二线单药疗法用于初治晚期非小细胞肺癌（NSCLC）患者的安全性和疗效。
符合条件的患者每3周静脉注射10 mg/kg伊沃西单抗（Q3W）、每2周静脉注射20 mg/kg（Q2W）、每3周静脉注射20 mg/kg或每3周静脉注射30 mg/kg。主要终点为依据实体瘤疗效评价标准1.1版评估的安全性和客观缓解率（ORR）。
在数据截止日期（2022年10月5日），108例患者入组并接受了伊沃西单抗治疗。74例患者（68.5%）的程序性死亡配体-1肿瘤比例评分（TPS）大于或等于1%，其中35例（32.4%）的TPS大于或等于50%。中位随访时间为10.4个月（范围：8.4 - 10.9个月）。所有患者的ORR和疾病控制率分别为39.8%和86.1%。TPS小于1%、大于或等于1%、大于或等于50%的患者的ORR分别为14.7%、51.4%和57.1%。在67例接受一线伊沃西单抗治疗的程序性死亡配体-1阳性患者中，10 mg/kg Q3W、20 mg/kg Q2W、20 mg/kg Q3W和30 mg/kg Q3W剂量组的ORR分别为33.3%、52.6%、60.0%和75.0%。24例患者（22.2%）发生了≥3级治疗相关不良事件（TRAEs）。导致治疗中断的TRAEs发生在1例患者（0.9%）中。导致死亡的TRAEs发生在3例鳞状NSCLC患者中（2.8%）。鳞状与非鳞状NSCLC患者中≥3级TRAEs和≥3级出血事件发生率分别为25.5%对18.9%和0.0%对1.9%。
伊沃西单抗单药疗法耐受性良好，在晚期或转移性NSCLC患者中显示出有前景的疗效。
美国国立医学图书馆临床试验标识符：NCT04900363
