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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1481326
This article is part of the Research Topic New Insights into Immune Regulation for Two Sides of the Same Coin: Cancer and Autoimmunity View all 4 articles
A novel anti-HER2 monoclonal antibody IAH0968 in HER2-positive heavily pretreated solid tumors: results from a phase Ia/Ib first-inhuman, open-label, single center study
Provisionally accepted
Na Song
1
Yuee Teng
1
Jing Shi
1
Zan Teng
1
Bo Jin
1
Jinglei Qu
1
Lingyun Zhang
1
Ping Yu
1
Lei Zhao
1
Jin Wang
1
Aodi Li
1
Linlin Tong
1
Shujie Jiang
1
Yang Liu
1
Liusong Yin
2
Xiaoling Jiang
2
Tie Xu
2
Jian Cui
3
Xiujuan Qu
1*
Yunpeng Liu
1*- 1 The First Affiliated Hospital of China Medical University, Shenyang, China
- 2 SUNHO (China) BioPharmaceutical Co., Ltd, Nanjing, China
- 3 Nanjing Jiening Pharmaceutical Technology Co., Ltd, Nanjing, China
Background: IAH0968 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.To 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).Results: Only 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. Conclusions: In HER2-positive heavily pretreated metastatic patients, IAH0968 demonstrated promising clinical activity with durable responses and tolerable safety profiles.
Keywords: HER2, IAH0968, clinical study, Safety, first-in-human
Received: 15 Aug 2024; Accepted: 14 Oct 2024.
Copyright: © 2024 Song, Teng, Shi, Teng, Jin, Qu, Zhang, Yu, Zhao, Wang, Li, Tong, Jiang, Liu, Yin, Jiang, Xu, Cui, Qu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiujuan Qu, The First Affiliated Hospital of China Medical University, Shenyang, China
Yunpeng Liu, The First Affiliated Hospital of China Medical University, Shenyang, China
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