HLX22 Receives FDA Orphan Drug Designation in Gastric Cancer

The FDA has granted orphan drug designation to the anti-HER2 monoclonal antibody HLX22 for the treatment of patients with gastric cancer.1

Data from the phase 2 HLX22-GC-201 study (NCT04908813) presented during the 2025 Gastrointestinal Cancers Symposium showed that among patients with gastric/gastroesophageal junction (GEJ) cancer who received HLX22 in combination with the trastuzumab biosimilar HLX02 (Hercessi), capecitabine, and oxaliplatin (n = 31), the median progression free survival (PFS) by independent radiology review committee (IRRC) assessment was not yet reached (NR; 95% CI, 23.5 months-not evaluable [NE]) vs 8.3 months (95% CI, 5.7-12.7) among those who received placebo in place of HLX22 (n = 31; HR, 0.2; 95% CI, 0.06-0.45).2 The 12-month PFS rates were 73.8% (95% CI, 50.3%-87.4%) and 34.2% (95% CI, 12.0%-58.1%), respectively, and the 24-month PFS rates were 61.5% (95% CI, 30.4%-82.0%) and 11.4% (95% CI, 0.8%-38.1%), respectively.

The objective response rate per IRRC assessment was 87.1% (95% CI, 70.2%-96.4%) in the HLX22 arm, with 1 patient achieving a complete response, compared with 80.6% (95% CI, 62.5%-92.5%) in the placebo arm (odds ratio, 1.6; 95% CI, 0.4-6.5). The median durations of response (DORs) were NR (95% CI, 22.1 months-NE) and 9.7 months (95% CI, 4.6-20.0), respectively (HR, 0.1; 95% CI, 0.04-0.41). The 12-month DOR rates were 78.5% (95% CI, 51.8%-91.4%) and 26.3% (95% CI, 5.1%-55.0%), respectively.

HLX22 binds to the HER2 extracellular subdomain IV at a different binding site than that of trastuzumab, enabling simultaneous binding of the 2 agents to HER2 dimers on the tumor cell surface.1

HLX22-GC-201 enrolled patients 18 to 80 years of age with histologically confirmed locally advanced or metastatic gastric/GEJ cancer that could not be cured with surgery.2 Eligible patients also needed to have an ECOG performance status of 0 or 1, have received no prior systemic antitumor therapy for advanced or metastatic disease, and have HER2-positive disease.

Patients were randomly assigned 1:1 to receive 15 mg/kg of intravenous (IV) HLX22 or placebo every 3 weeks, both in combination with HLX02 at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses every 3 weeks. Patients in both arms also received IV oxaliplatin on day 1 every 3 weeks for up to 8 cycles and oral capecitabine twice daily on days 1 to 14 of each cycle for up to 2 years.

The primary end points were ORR and PFS per RECIST 1.1 criteria assessed by IRRC. Secondary end points included investigator-assessed PFS and ORR, overall survival (OS), DOR, quality of life (QOL), safety, pharmacokinetics, and immunogenicity.

In terms of safety, any-grade treatment-emergent adverse effects (TEAEs) occurred at rates of 96.8% and 100% in the HLX22 and placebo arms, respectively. Grade 3 or greater TEAEs (54.8% vs 48.4%) and TEAEs leading to treatment discontinuation (9.7% vs 22.6%) were reported in both arms. No patients experienced TEAEs leading to death in the investigational arm; 4 patients died due to TEAEs in the control arm. The most common any-grade TEAEs in both arms included decreased platelet counts (80.6% vs 74.2%), decreased neutrophil counts (80.6% vs 54.8%), anemia (58.1% vs 61.3%), and decreased white blood cell counts (58.1% vs 58.1%).

In November 2024, Henlius Biotech announced that the first patient had been dosed in the phase 3 HLX22-GC-301 study (NCT06532006).3 HLX22-GC-301 is a double-blind, randomized, controlled multicenter trial that is comparing HLX22 in combination with trastuzumab and chemotherapy vs trastuzumab and chemotherapy, with or without pembrolizumab, for the frontline treatment of patients with HER2-positive locally advanced or metastatic gastric/GEJ cancer. The primary end points are PFS and OS per RECIST 1.1 criteria assessed by IRRC. Secondary end points include investigator-assessed PFS, ORR, DOR, QOL, safety, immunogenicity, and pharmacokinetics.

References

1. Henlius receives orphan-drug designation for HLX22(innovative anti-HER2 mAb) in the U.S. for gastric cancer. News release. Shanghai Henlius Biotech. March 19, 2025. Accessed March 19, 2025. https://www.henlius.com/en/NewsDetails-4914-26.html
2. Li J, Li N, Yang M, 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. J Clin Oncol. 2025;43(suppl 4):440. doi:10.1200/JCO.2025.43.4_suppl.440
3. First patient dosed in phase 3 MRCT of dual HER2 blockade therapy for HER2+ GC. News release. Shanghai Henlius Biotech. November 22, 2024. Accessed March 19, 2025. https://www.henlius.com/en/NewsDetails-4765-26.html