Henlius Advances HLX22 Phase 3 Trial for HER2-Positive Gastric Cancer at ASCO GI 2026
Key Insights
Henlius presents the design of HLX22-GC-301, an international Phase 3 head-to-head trial comparing HLX22 plus trastuzumab against current standard of care for HER2-positive gastric cancer (search).
The novel anti-HER2 (search) monoclonal antibody HLX22 binds to a different epitope than trastuzumab, enabling simultaneous binding and resulting in 40-80% increased HER2 internalization.
Phase 2 data showed median overall survival was not reached with HLX22 combination versus 16.4 months for control, with an 80% reduction in disease progression risk.
Henlius (2696.HK) unveiled the design of its pivotal Phase 3 trial HLX22-GC-301 at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), marking a significant milestone in the development of HLX22, a novel epitope-targeting anti-HER2 (search) monoclonal antibody for HER2-positive gastric cancer (search).
Innovative Mechanism of Action
HLX22 represents a differentiated approach to HER2 (search) targeting through its unique molecular design. The antibody binds to HER2 extracellular subdomain IV at a binding site distinct from trastuzumab, enabling simultaneous binding of both HLX22 and trastuzumab to HER2 dimers on tumor cell surfaces. This dual binding mechanism results in a 40-80% increase in HER2 internalization compared to trastuzumab alone.
Promising Phase 2 Results Support Phase 3 Development
Prior to initiating the Phase 3 trial, Henlius conducted the HLX22-GC-201 Phase 2 study evaluating HLX22 in combination with trastuzumab in patients with HER2-positive gastric cancer (search). With long-term follow-up exceeding two years, the study demonstrated sustained clinical benefit with favorable trends in both overall survival and progression-free survival.
The Phase 2 data showed median overall survival was not reached (95% CI: 16.2, NE) in the HLX22 combination group compared with 16.4 months (95% CI: 10.7, NE) in the control group (HR = 0.60; 95% CI: 0.28-1.21). Median progression-free survival was not reached (95% CI: 16.2, NE) versus 8.3 months (95% CI: 5.7-21.4) respectively (HR=0.20; 95% CI: 0.09-0.54), indicating an 80% reduction in the risk of disease progression or death.
Global Phase 3 Trial Design
HLX22-GC-301 is a randomized, double-blind, two-arm international Phase 3 clinical study designed to compare the efficacy and safety of HLX22 in combination with trastuzumab and XELOX (search) versus trastuzumab and XELOX with or without pembrolizumab in patients with HER2 (search)-positive advanced gastric or gastroesophageal junction cancer (search).
The trial will enroll approximately 550 eligible patients from multiple regions globally, randomly assigned in a 1:1 ratio to receive either HLX22 (15 mg/kg) plus trastuzumab and XELOX (search) with placebo for pembrolizumab, or placebo for HLX22 plus trastuzumab and XELOX with or without pembrolizumab. HLX22 will be administered intravenously on Day 1 of each 21-day treatment cycle until loss of clinical benefit, death, intolerable toxicity, or withdrawal of consent.
Study Population and Endpoints
Key inclusion criteria include histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 (search)-positive gastric or gastroesophageal junction adenocarcinoma. The trial excludes patients with prior use of any HER2-targeted therapy.
Stratification factors include HER2 (search) immunohistochemistry status (3+ vs 2+), geographic region (Asia vs Europe/North America vs rest of the world), primary tumor site (gastric vs gastroesophageal junction), and tumor PD-L1 (search) expression levels. Notably, the trial does not restrict enrollment based on PD-L1 expression status, aiming to overcome clinical limitations of current first-line treatment paradigms.
The dual primary endpoints are progression-free survival assessed by independent radiology review committee per RECIST v1.1 and overall survival. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, progression-free survival on subsequent therapy, duration of response, safety, pharmacokinetics, immunogenicity, and quality of life.
Regulatory Recognition and Global Development
HLX22 has received Orphan Drug Designation for gastric cancer from both the U.S. FDA (search) and the European Commission in 2025, highlighting its global development prospects and clinical value. The Phase 3 trial has been approved and initiated across multiple countries including China, the United States, Japan, Australia, and Argentina.
The trial is co-led by Dr. Lin Shen of Peking University Cancer Hospital (search) and Dr. Jaffer A. Ajani of MD Anderson Cancer Center, who also chairs the NCCN Guidelines Panel for Gastric and Esophageal Cancers. Beyond gastric cancer, Henlius has recently initiated a Phase 2 clinical trial (HLX22-BC201) evaluating HLX22 in combination with trastuzumab deruxtecan as second-line therapy for HER2 (search)-low, hormone receptor-positive locally advanced or metastatic breast cancer, with the first patient dosed in China.