Shanghai, China, April 28, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the application for clinical trial for head-to-head phase 3 international multicenter clinical study (HLX22-GC-301) of Henlius’ novel anti-HER2 mAb, HLX22, in combination with trastuzumab and chemotherapy for the first-line treatment of HER2-positive advanced gastric cancer has been approved in Germany. Previously, the first patient was dosed in China, Japan, and Australia, and the study has obtained investigational new drug (IND) approvals in countries and regions including the United States (U.S.) and Korea. Besides, HLX22 has been granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA). As of now, no similar dual HER2 blockade therapy for the treatment of HER2-positive gastric cancer has received approval for commercialization globally.
Until now, gastric/gastroesophageal junction (G/GEJ) cancer still constitutes a major global health problem. Globally, there were around 1 million new cases in 2022 [1]. G/GEJ cancer generally carries a poor prognosis since it is often diagnosed at an advanced stage, with a 5-year relative survival rate of only 6% [2,3]. The reported rates of HER2 positivity in patients with gastric cancer range from 12% to 23%, and the prognosis for patients with HER2-positive disease used to be even worse than those with HER2-negative disease [2-4]. Currently, for patients with HER2-positive locally advanced/metastatic G/GEJ cancer, the current standard first-line treatment is trastuzumab plus chemotherapy. Immunotherapies are recommended to be added for tumours with PD-L1 expression levels by CPS (Combined Positive Score) of greater than 1. However, the effectiveness and prognosis for these treatments need to be further improved [5].
HLX22, an innovative anti-HER2 mAb, 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. Results from HLX22-GC-201, a phase 2 study of HLX22 in combination with trastuzumab injection (HLX02) and XELOX, as first-line therapy for HER2-positive locally advanced or metastatic gastric cancer patients showed that the addition of HLX22 to HLX02 (trastuzumab) plus chemotherapy as first-line therapy improved efficacy in HER2-positive G/GEJ cancer patients with manageable safety [6-8]. Updated results were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) [9].
HLX22-GC-301 is a double-blind, randomized, controlled multicenter phase 3 study aims to compare the efficacy and safety of HLX22 in combination with trastuzumab and chemotherapy versus trastuzumab and chemotherapy with or without pembrolizumab as first-line treatment in patients with HER2-positive, locally advanced or metastatic gastric/gastroesophageal junction cancer. Eligible participants will be randomized at 1:1 to the experimental arm (treated with HLX22 (15 mg/kg, intravenous injection) plus trastuzumab and chemotherapy) or the control group (placebo plus trastuzumab and chemotherapy with or without pembrolizumab). The primary endpoints of this study are progression-free survival (PFS) accessed by independent radiology review committee (IRRC) per RECIST 1.1 and overall survival (OS), the secondary endpoints include investigator-assessed PFS, IRRC or investigator-accessed objective response rate (ORR), PFS2, duration of response (DOR), quality of life, safety, immunogenicity, and pharmacokinetic characteristics.
Apart from gastric cancer, the company initiated a phase 2 clinical trial of HLX22, in combination with trastuzumab deruxtecan (T-DXd) for the treatment of HER2-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer and completed the first patient dosage in China. Moving forward, the company will continue to uphold a patient-centric approach, focus on unmet medical needs, and actively explore the optimization of combination therapies for HER2-positive cancer. This includes advancing clinical development for HLX22 to bring hope to more patients around the world.
References
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
[2] Ajani JA. et al. J Natl Compr Canc Netw 2022;20(2):167-92.
[3] Alsina M. et al. Nat Rev Gastroenterol Hepatol 2023;20(3):155-70.
[4] Gravalos C. et al. Ann Oncol 2008;19(9):1523-9.
[5] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.1.2024
[6] Zhu X, Ding Y, Wang Q, Yang G, Zhou L, Wang Q. 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. doi:10.1007/s10637-023-01338-7
[7] 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).DOI:10.1200/JCO.2024.42.3_suppl.354
[8] J. Li et al., 422P HLX22 plus HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric/gastroesophageal junction cancer: Updated results from a randomized, double-blind phase II study, Annals of Oncology,Annals of Oncology (2024) 35 (suppl_1): S162-S204. 10.1016/annonc/annonc1482
[9] Li, Jin, et al. "HLX22 plus trastuzumab and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC): Updated results with additional patients." (2025): 440-440.