Shanghai, China, July 14, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient in the United States has been dosed in the company’s international multicentre phase 3 head-to-head clinical trial (HLX22-GC-301) comparing its novel anti-HER2 monoclonal antibody (mAb) HLX22 in combination with trastuzumab and chemotherapy with the current first-line standard of care therapy (trastuzumab + chemotherapy ± pembrolizumab) as the first-line treatment for HER2-positive advanced gastric cancer. As of now, no similar dual HER2 blockade therapy for the treatment of HER2-positive gastric cancer has received approval for commercialization globally.
The study is co-led by Prof. Lin Shen from Peking University Cancer Hospital and Professor Jaffer A. Ajani (MD Anderson Cancer Center; Chair of the NCCN Guidelines Panel for Gastric and Esophageal Cancers), and has previously dosed first patients in China, Japan, Australia, and South Korea, with investigational new drug (IND) approvals obtained in Chile, Brazil, Argentina and other countries and regions. HLX22 has been granted Orphan Drug Designation (ODD) by both the US Food and Drug Administration (FDA) and the European Commission (EC) for the treatment of gastric cancer.
Until now, gastric cancer still constitutes a major global health problem. According to GLOBOCAN 2022, there were around 1 million new cases and over 660 thousand new deaths of gastric cancer in 2022 globally [1]. Gastric cancer is often diagnosed at an advanced stage, with a poor prognosis and a 5-year relative survival rate of only 6% [2,3]. Despite the advancements in targeted therapies, such as anti-HER2 agents, and immune checkpoint inhibitors (anti-PD-1/PD-L1 mAbs) for gastric cancer treatment in recent years [4], the disease's high molecular heterogeneity leads to markedly varied responses to chemotherapy, targeted therapy, and immunotherapy across different subtypes [5]. Immunotherapy remains limited to PD-L1 positive populations with only modest efficacy improvements. This underscores the urgent unmet clinical needs in the overall management of HER2 positive gastric cancer.
HLX22, an innovative anti-HER2 mAb, can bind to HER2 extracellular subdomain IV at a binding site different from that of trastuzumab via differentiated molecular design and mechanism of action, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumour cell surface, resulting in a 40%–80% increase in HER2 internalisation. Updated results from a phase 2 study (HLX22-GC-201) of HLX22 in combination with HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) and chemotherapy as a first-line treatment for HER2-positive advanced gastric cancer were presented at ASCO 2025 [6]. The data demonstrated that the efficacy benefit of HLX22 in HER2-positive gastric cancer remained stable with extended follow-up (median follow-up exceeding two years), outperforming previous data.
This 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 gastroesophageal junction cancer and gastric cancer. Eligible participants will be randomized at 1:1 to the experimental arm (treated with HLX22 (15 mg/kg) in combination with 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) assessed by independent radiology review committee (IRRC) per RECIST v1.1 and overall survival (OS), the secondary endpoints include investigator-assessed PFS, IRRC or investigator-assessed objective response rate (ORR), PFS2, duration of response (DOR), quality of life, safety, immunogenicity and pharmacokinetic characteristics.
Beyond gastric cancer, Henlius has also recently initiated a phase 2 clinical trial (HLX22-BC201) of HLX22 in combination with trastuzumab deruxtecan (T-DXd) as second-line therapy for HER2-low, hormone receptor (HR)-positive locally advanced or metastatic breast cancer and has dosed the first patient in China. Moving forward, Henlius will continue to explore the therapeutic potential of novel HER2-targeted therapies in tumours, accelerating HLX22’s global development to deliver more affordable and effective treatment options for patients worldwide.
Reference
[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] Miao, ZF.,et al. Progress and remaining challenges in comprehensive gastric cancer treatment. Holist Integ Oncol 1, 4 (2022).
[5] Guan, WL.,et al. Gastric cancer treatment: recent progress and future perspectives. J Hematol Oncol 16, 57 (2023).
[6] Jin Li 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.. JCO 43, 440-440(2025). DOI:10.1200/JCO.2025.43.4_suppl.440