2. Academic Validation
  3. KN026 (anti-HER2 bispecific antibody) in patients with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancer

KN026 (anti-HER2 bispecific antibody) in patients with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancer

  • Eur J Cancer. 2023 Jan:178:1-12. doi: 10.1016/j.ejca.2022.10.004.
Jianming Xu 1,  Jieer Ying 2,  Rongrui Liu 3,  Jun Wu 4,  Feng Ye 5,  Nong Xu 6,  Yanqiao Zhang 7,  Rusen Zhao 8,  Xiaojun Xiang 9,  Jianhong Wang 10,  Xiaoyan Lin 11,  Huiting Xu 12,  Shegan Gao 13,  Suxia Luo 14,  Baohong Guo 15,  Xionghui Li 15,  Yangzhi Su 16,  Qian Wang 16
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Oncology, The Fifth Medical Center of the PLA General Hospital, Beijing, China. Electronic address: jmxu2003@163.com.
  • 2 Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China.
  • 3 Department of Gastrointestinal Oncology, The Fifth Medical Center of the PLA General Hospital, Beijing, China.
  • 4 Department of Oncology, The First People's Hospital of Changzhou, Changzhou, China.
  • 5 Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
  • 6 Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 7 Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
  • 8 Department of Medical Oncology, Zibo Municipal Hospital, Zibo, China.
  • 9 Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 10 Department of Medical Oncology, Nantong Tumor Hospital, Nantong, China.
  • 11 Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
  • 12 Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, China.
  • 13 Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
  • 14 Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, China.
  • 15 Alphamab Oncology Ltd., Suzhou, China.
  • 16 Department of Medicine, CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, China.
PMID: 36370604 DOI: 10.1016/j.ejca.2022.10.004
Abstract

Background: KN026 is a novel human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody that binds two distinct domains of HER2. We report the safety and efficacy results of the phase 2 trial in patients with advanced HER2-expressing gastric or gastroesophageal junction Cancer who failed from at least one prior line of standard treatment.

Material and methods: In this open-label, multicentre, phase 2 trial, eligible patients were enrolled in the high-level HER2 cohort or low-level HER2 cohort and assigned to receive KN026 10 mg/kg (once a week), 20 mg/kg (once every two weeks) or 30 mg/kg (once every three weeks) intravenously. The primary end-points were the objective response rate (ORR) and duration of response assessed according to Response Evaluation Criteria in Solid Tumours (version 1.1).

Results: Between 17th June 2019 and 23rd August 2021, 45 patients were enrolled and received at least one dose of KN026, including 27 patients in the high-level HER2 cohort, 14 patients in the low-level HER2 cohort and four patients who had no HER2 expression. The ORR in the high-level HER2 cohort was 56% (95% confidence interval [CI] 35%-76%), with a durable response duration of 9.7 months (95% CI 4.2-not evaluable); while for the patients with low-level HER2, the ORR was 14% (95% CI 2%-43%). The most frequent ≥ grade 3 treatment-emergent adverse events were gastrointestinal disorders (five patients, 11%). No drug-related deaths were reported.

Conclusions: KN026 showed a favourable safety profile and promising anti-tumour activity. Our results support further studies evaluating KN026 and the combination treatment with Other active drugs in patients with advanced gastric or gastroesophageal junction Cancer having high-level HER2 expression.

Keywords

Bispecific monoclonal antibodies; Gastric neoplasms; Human epidermal growth factor receptor 2.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P99437
    99.22%, Anti-HER2 Antibody