Shanghai, China, December 4, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 2 clinical trial of the company’s novel anti-HER2 monoclonal antibody (mAb), HLX22, in combination with trastuzumab and chemotherapy or combined with trastuzumab deruxtecan (T-DXd) has been approved by the China National Medical Products Administration (NMPA), for the treatment of HER2-expressing solid tumours. As a novel HER2-targeting mAb, HLX22 has a synergistic anti-tumor effect in combination with trastuzumab. The dual-HER2 blockade therapy has demonstrated anti-tumor efficacy and good safety in investigational studies for the first-line treatment of advanced gastric cancer[1,2]. Therefore, Henlius intends to further explore the efficacy and safety of HLX22-based anti-HER2 therapies in various types of solid tumours, expected to bring clinical benefits to a wider group of patients with solid tumours.
Epidermal growth factor receptor (EGFR) family signaling contributes to neoplastic cell growth, malignant transformation, and resistance to chemotherapy. Human epidermal growth factor receptor 2 (HER2) belongs to human EGFR family, including EGFR (HER1), HER3, and HER4[3]. From which, the HER2 alterations, including HER2 mutation, HER2 amplification and HER2 overexpression have been found in a broad spectrum of tumour types, such as breast cancer, gastric cancer, biliary tract cancer, pancreatic cancer, uroepithelial cancer, and lung cancer, making it a well-established therapeutic target in tumours treatment[4]. The research and development of anti-HER2 therapeutics has significantly improved the survival of HER2- positive breast cancer and gastric cancer patients[5,6]. Moreover, with advances in HER2-targeting agents like dual anit-HER2 therapy and antibody drug conjugates (ADCs), HER2-targeted therapeutics have expanded to other tumour types beyond breast cancer and gastric cancer, providing new treatment options for these patients[7].
HLX22 is an innovative anti-HER2 mAb introduced from AbClon, Inc. and further investigated and developed by Henlius. HLX22 can bind to HER2 extracellular subdomain IV at a binding site different from that of trastuzumab, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumour cell surface, thereby promoting the internalization and HER2 dimer degradation. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab synergistically inhibited tumour cell proliferation and apoptosis, which led to enhanced anti-tumour activity in vitro and in vivo. A phase 1 clinical trial of HLX22 demonstrates that HLX22 was well tolerated and had a favorable safety profile[8].And HLX22-GC-201，the phase 2 clinical trial of HLX22 combined with trastuzumab showed that adding HLX22 to HLX02 (trastuzumab for injection) + XELOX improved survival and anti-tumour response in patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer in the first-line setting, with a manageable safety profile[1,2] . Up to date, the phase 3 international multicenter clinical study of HLX22 in combination of trastuzumab and chemotherapy for the treatment of HER2 positive advanced G/GEJ cancer has received regulatory approvals in China, the U.S., Japan and Australia, respectively. And the first subject has been dosed for this MRCT in China.
Looking forward, Henlius will actively improve efficiency through innovations, with a particular focus on addressing the unmet medical needs. This includes continuing to explore the therapeutic potential of novel HER2 dual-target therapies in oncology, efficiently promoting the global clinical development of HLX22, so as to provide more high-quality and affordable therapies for patients worldwide.
【Reference】
[1] Li N, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2.
[2] Jin Li, et al., HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study. JCO 42, 354-354(2024).
[3] Omar N, et al. HER2-an emerging biomarker in non-breast and non-gastric cancers. Pathogenesis. 2015;2(3):1-9.
[4] Cheng X. A Comprehensive Review of HER2 in Cancer Biology and Therapeutics. Genes (Basel). 2024 Jul 11;15(7):903.
[5] Marra, Antonio et al. Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives. Nature reviews. Clinical oncology vol. 21,3 (2024): 185-202.
[6] Bang YJ, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial [published correction appears in Lancet. 2010 Oct 16;376(9749):1302]. Lancet. 2010;376(9742):687-697.
[7] Yoon J, et al. HER2-targeted therapies beyond breast cancer - an update. Nat Rev Clin Oncol. 2024 Sep;21(9):675-700. Epub 2024 Jul 22.
[8] Zhu X, et al. HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial. Invest New Drugs. 2023;41(3):473-482.