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
  • 1. Department of Gastrointestinal Oncology, The Fifth Medical Center of the PLA General Hospital, Beijing, China. Electronic address: [email protected].
  • 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.
Products