Frontiers in Immunology (Nov 2024)
A novel anti-HER2 monoclonal antibody IAH0968 in HER2-positive heavily pretreated solid tumors: results from a phase Ia/Ib first-in-human, open-label, single center study
- Na Song,
- Na Song,
- Yuee Teng,
- Yuee Teng,
- Jing Shi,
- Jing Shi,
- Zan Teng,
- Zan Teng,
- Bo Jin,
- Bo Jin,
- Jinglei Qu,
- Jinglei Qu,
- Lingyun Zhang,
- Lingyun Zhang,
- Ping Yu,
- Ping Yu,
- Lei Zhao,
- Lei Zhao,
- Jin Wang,
- Jin Wang,
- Aodi Li,
- Aodi Li,
- Linlin Tong,
- Linlin Tong,
- Shujie Jiang,
- Shujie Jiang,
- Yang Liu,
- Yang Liu,
- Liusong Yin,
- Xiaoling Jiang,
- Tie Xu,
- Jian Cui,
- Xiujuan Qu,
- Xiujuan Qu,
- Yunpeng Liu,
- Yunpeng Liu
Affiliations
- Na Song
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Na Song
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yuee Teng
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yuee Teng
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Jing Shi
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Jing Shi
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Zan Teng
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Zan Teng
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Bo Jin
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Bo Jin
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Jinglei Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Jinglei Qu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Lingyun Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Lingyun Zhang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Ping Yu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Ping Yu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Lei Zhao
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Lei Zhao
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Jin Wang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Jin Wang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Aodi Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Aodi Li
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Linlin Tong
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Linlin Tong
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Shujie Jiang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Shujie Jiang
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yang Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yang Liu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Liusong Yin
- Department of Clinical Medicine, SUNHO (China) BioPharmaceutical Co., Ltd, Nanjing, China
- Xiaoling Jiang
- Department of Clinical Medicine, SUNHO (China) BioPharmaceutical Co., Ltd, Nanjing, China
- Tie Xu
- Department of Clinical Medicine, SUNHO (China) BioPharmaceutical Co., Ltd, Nanjing, China
- Jian Cui
- Department of Clinical Medicine, Nanjing Jiening Pharmaceutical Technology Co., Ltd, Nanjing, China
- Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Xiujuan Qu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
- Yunpeng Liu
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China
- DOI
- https://doi.org/10.3389/fimmu.2024.1481326
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundIAH0968 is an afucosylated anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody which improved the activity of antibody-dependent cellular cytotoxicity (ADCC) and superior anti-tumor efficacy.MethodsTo determine the maximum tolerated dose (MTD) with dose-limiting toxicity (DLT), a single institution, phase Ia/Ib study was undertaken, using 3 + 3 design. The primary endpoints were safety, tolerability and preliminary clinical activity. Eighteen patients were evaluable for safety and fifteen patients were suitable for efficacy analysis. Dose escalations were 6 mg/kg (N = 2), 10 mg/kg (N = 7), 15 mg/kg (N = 5), and tolerable up to 20 mg/kg (N = 4).ResultsOnly one DLT was found at dosage 10 mg/kg, and no MTD was reached. The most common Grade 3 treatment-related adverse events (TRAEs) were hypokalemia (5.6%), supraventricular tachycardia (5.6%), interval extension of QTC (5.6%), and infusion reaction (5.6%). Grade 4 TRAE was arrhythmia (5.6%). No serious TRAE or Grade 5 was reported. 22.2% of patients had a TRAE leading to dose adjustment and 16.7% of patients had a TRAE resulting in discontinuation of IAH0968. After a median follow-up of 9.7 months (range, 3.7 - 22.0), the objective response rate (ORR) was 13.3% (2/15), the disease control rate (DCR) was 53.3% (8/15), and median progression-free survival (mPFS) was 4.2 months (95% CI: 1.4 - 7.7), and the median duration of disease control (DDC) was 6.3 months (95% CI: 2.9–not reached), with 4/15 responses ongoing.ConclusionsIn HER2-positive heavily pretreated metastatic patients, IAH0968 demonstrated promising clinical activity with durable responses and tolerable safety profiles.Clinical trial registrationClinicalTrials.gov, identifier NCT04934514.
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