Henlius presented updated clinical data from a Phase 2 study (HLX22-GC-201) evaluating HLX22, a novel anti-HER2 monoclonal antibody, in combination with trastuzumab (HLX02) and chemotherapy for the first-line treatment of HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer at the 2024 ESMO Gastrointestinal Cancers Congress. The study, led by Professor Jin Li of Shanghai East Hospital, School of Medicine, Tongji University, suggests that the addition of HLX22 to trastuzumab and chemotherapy may improve outcomes for patients with this aggressive cancer.
Dual HER2 Blockade Strategy
Currently, the standard first-line treatment for HER2-positive locally advanced/metastatic G/GEJ cancer is trastuzumab plus chemotherapy, with immunotherapies added for tumors with high PD-L1 expression. However, there remains a need for more effective and durable treatments. HLX22 offers a potential new approach through dual HER2 blockade.
HLX22, in-licensed from AbClon, Inc., binds to HER2 subdomain IV, a distinct site from trastuzumab. This allows HLX22 and trastuzumab to bind simultaneously to HER2, potentially enhancing antitumor activity. Preclinical studies have demonstrated that this combination inhibits cell proliferation induced by epidermal growth factor (EGF) and Histidine-Rich Glycoprotein 1 (HRG1), leading to enhanced antitumor activity in vitro and in vivo.
HLX22-GC-201 Study Results
Results from the HLX22-GC-201 study, initially presented at the 2024 ASCO Gastrointestinal Cancers Symposium, indicated that adding HLX22 to HLX02 (trastuzumab) and chemotherapy prolonged progression-free survival and enhanced antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile. The updated data were presented in a poster session (Abstract Number: 422P) at the ESMO GI Congress.
Implications and Future Directions
G/GEJ cancer remains a significant global health problem, with approximately 1 million new cases in 2022. The 5-year relative survival rate is only 6% due to late-stage diagnosis. HER2 positivity is observed in 12% to 23% of gastric cancer patients. The FDA has approved an investigational new drug application (IND) for a Phase 3 international multicenter clinical study of HLX22 in combination with trastuzumab and chemotherapy for the first-line treatment of HER2-positive advanced gastric cancer. This Phase 3 trial will further evaluate the efficacy and safety of this novel dual HER2 blockade strategy.
