September 23, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the company’s novel epitope HER2-targeting monoclonal antibody, HLX22, has completed first patient dosing in Argentina for its international multicentre Phase 3 trial (HLX22-GC-301). This marks the first clinical milestone of HLX22 in Latin America, extending Henlius’ global clinical operations beyond China, Australia, the U.S., Japan, and South Korea, and further broadening its worldwide clinical development footprint.
HLX22-GC-301 is a randomized, double-blind, international Phase 3 trial directly comparing HLX22 in combination with trastuzumab and chemotherapy versus the current first-line standard of care (trastuzumab + chemotherapy ± pembrolizumab) for HER2-positive advanced gastric cancer. The trial is co-led by Dr. Lin Shen of Peking University Cancer Hospital and Dr. Jaffer A. Ajani (MD Anderson Cancer Centre; Chair of the NCCN Guidelines Panel for Gastric and Esophageal Cancers). The trial has already been approved and initiated in China, the U.S., Japan, Australia, and other countries and regions.
HLX22 is a differentiated HER2-targeting monoclonal antibody that binds to a novel epitope on the HER2 extracellular domain. It can bind HER2 simultaneously with trastuzumab, effectively promoting internalization and degradation of HER2 homodimers and HER2/EGFR heterodimers. Preclinical studies demonstrated HLX22 increases HER2 internalization efficiency by 40–80%, leading to stronger HER2 blockade. Importantly, HLX22-GC-301 does not limit enrolment by PD-L1 status, aiming to overcome clinical limitations of current first-line treatment for HER2-positive gastric cancer. In recognition of its potential, HLX22 has been granted Orphan Drug Designation (ODD) for gastric cancer by both the U.S. FDA and the European Commission in 2025, highlighting its global development prospects and clinical value.
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.
The first dosing in Latin America marks not only a key milestone in Henlius’ globalization journey, but also reaffirms the company’s commitment to advancing differentiated innovation under international standards and accelerating the worldwide reach of China’s biopharmaceutical innovations. Looking ahead, Henlius will continue to expand its global clinical footprint and bring innovative, affordable treatment options to more patients around the world.
【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
About HLX22
HLX22, a monoclonal antibody targeting a novel epitope of HER2, 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.
About HLX22-GC-301
This double-blind, randomized, controlled multicentre phase 3 trial 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 trial 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.
