FDA Grants Orphan Drug Designation to HLX22 for Gastric Cancer Treatment

US FDA

• The FDA has granted orphan drug designation to HLX22 for the treatment of patients with gastric cancer.
• HLX22 is an anti-HER2 monoclonal antibody (mAb).
• A multicenter, phase 3 trial (NCT04908813) is evaluating HLX22 in this space across multiple countries and regions, including the US, China, Japan, and Australia.

The FDA has granted orphan drug designation to HLX22, an innovative anti-HER2 mAb, for the treatment of patients with gastric cancer.¹

This designation provides HLX22 with several development incentives, including tax credits for clinical trial costs, waiver of application fees for new drugs, and 7 years of market exclusivity upon approval. These benefits aim to accelerate the development and availability of HLX22, enabling patients, particularly those with HER2-positive metastatic gastric (GI) or gastroesophageal junction (GEJ) cancer, to access this therapy sooner.

The orphan drug designation for HLX22 follows the initiation of a multicenter, phase 3 clinical trial titled HLX22-GC-301. This global study is being conducted across the US, China, Japan, and Australia, and plans to evaluate the efficacy and safety of HLX22 when given in combination with trastuzumab (Herceptin) and chemotherapy as a first-line treatment for patients with HER2-positive metastatic GI or GEJ cancer. The first patient has already been dosed in the study.

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Mechanism of Action of HLX22

HLX22 is a novel anti-HER2 monoclonal antibody that targets the HER2 extracellular subdomain IV. Its molecular design allows the agent to bind simultaneously with trastuzumab to HER2 dimers on the surface of tumor cells.¹

By promoting the internalization and degradation of these HER2 dimers, HLX22 enhances antitumor activity and addresses mechanisms of resistance that may limit the efficacy of existing HER2-targeted therapies.¹

Preclinical and clinical data suggest that HLX22, when combined with trastuzumab and chemotherapy, significantly improves survival and antitumor efficacy in patients with HER2-positive GI/GEJ cancer. This combination has already demonstrated a manageable safety profile in phase 2 clinical trials.

Phase 3 Trial of HLX22

The ongoing, randomized, double-blind, placebo-controlled, phase 3 trial is evaluating the efficacy and safety of HLX22 plus the trastuzumab biosimilar trastuzumab-strf (Hercessi; formerly HLX02), capecitabine, and oxaliplatin in patients with HER2-positive GI/GEJ cancer.²

The trial is divided into 2 parts, with the current focus on part 1, which compares 3 treatment arms:

• Group A: HLX22 given at 25 mg/kg plus trastuzumab-strf, capecitabine, and oxaliplatin
• Group B: HLX22 at 15 mg/kg plus trastuzumab-strf, capecitabine, and oxaliplatin
• Group C: Placebo plus trastuzumab-strf and capecitabine, and oxaliplatin

Primary end points of the study include progression-free survival and objective response rate, assessed by an independent review committee using RECIST v1.1 criteria. Secondary end points will evaluate additional efficacy measures and safety data.

As of July 30, 2023, a total of 53 patients were randomized across the 3 groups. At a median follow-up of 14.3 months, the addition of HLX22 to trastuzumab-strf, capecitabine, and oxaliplatin demonstrated improved survival and antitumor response compared with those in the placebo group.

For safety, treatment-related adverse events (TRAEs) were observed in 94.1% to 100% of patients across the groups, with serious TRAEs occurring in 5.6% to 27.8% of patients. Only 1 patient in the placebo group experienced a grade 5 TRAE.

REFERENCES:

1. Henlius receives orphan drug designation for innovative anti-HER2 mAb HLX22 in the U.S. for gastric cancer. News release. Shanghai Henlius Biotech, Inc. March 19, 2025. Accessed March 19, 2025. https://tinyurl.com/53svn4bw

2. Li N, Qiu M, Zhang Y, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2. doi:10.1016/j.medj.2024.06.004