At the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI 2026), Henlius announced the presentation of the trial design for HLX22-GC-301, a international, randomised, double-blind, multicentre phase 3 head-to-head study evaluating HLX22, a novel epitope-targeting anti-HER2 monoclonal antibody, as a first-line treatment for patients with HER2-positive advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC). The trial design was presented in a poster session at the meeting.
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, Argentina, and other countries and regions. Importantly, the trial does not restrict enrolment based on PD-L1 expression status, and is aimed to support the continued evolution of global first-line treatment strategies for 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.
Prior to the initiation of the phase 3 trial, Henlius conducted a phase 2 clinical study (HLX22-GC-201) evaluating HLX22 in combination with HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) in patients with HER2-positive gastric cancer, with interim results previously reported. With long-term follow-up exceeding two years, the study showed that the HLX22-based combination demonstrated sustained clinical benefit in patients with HER2-positive gastric cancer, with favourable trends observed in both overall survival (OS) and progression-free survival (PFS).
Median OS was not reached (95% CI: 16.2, NE) compared with 16.4 months (95% CI: 10.7, NE) in the control group (HR = 0.60; 95% CI: 0.28–1.21). Median PFS 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). These results indicate an 80% reduction in the risk of disease progression or death, substantially exceeding historical trials, and provided important support for the design and implementation of the phase 3 head-to-head HLX22-GC-301 study.
HLX22-GC-301 is a randomized, double-blinded, two-arm international phase 3 clinical study aims to compare the efficacy and safety of HLX22 in combination with trastuzumab and XELOX versus trastuzumab and XELOX with or without (±) pembrolizumab in patients with HER2-positive, advanced G/GEJ cancer and no prior antitumor therapy in the advanced setting. The study’s key inclusion criteria include histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2-positive G/GEJ adenocarcinoma. Key exclusion criteria include prior use of any HER2-target therapy. Approximately 550 eligible patients will be enrolled from multiple regions across the globe and randomly assigned in a 1:1 ratio to receive HLX22 (15 mg/kg) + trastuzumab + XELOX ± placebo (for pembrolizumab) or placebo (for HLX22) + trastuzumab + XELOX ± pembrolizumab. HLX22 will be administered intravenously on Day 1 of each 21-day treatment cycle until loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent, or other reasons. The stratification factors include HER2 immunohistochemistry (3+ vs 2+), geographic region (Asia vs Europe/North America vs rest of the world), primary tumour site (gastric vs gastroesophageal junction), and tumour PD-L1 expression (CPS < 1 or not evaluable vs 1 ≤ CPS < 10 vs CPS ≥ 10). The dual primary endpoints are PFS assessed by independent radiology review committee per RECIST v1.1 and overall survival. Secondary endpoints include investigator-assessed PFS, objective response rate, PFS on the subsequent line of therapy, duration of response, safety, pharmacokinetics, immunogenicity, and quality of life.
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. 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.