HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial.

HLX22 is a novel monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). This first-in-human, phase 1 dose-escalation study aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HLX22 in patients with advanced solid tumors who had failed or were intolerant to standard therapies. Enrolled patients aged 18 to 75 years with histologically confirmed HER2-overexpressing advanced or metastatic solid tumors received intravenous HLX22 once every 3 weeks at 3, 10, and 25 mg/kg. Primary endpoints were safety and the maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy. Between July 31, 2019, and December 27, 2021, 11 patients were enrolled to receive HLX22 at 3 (n = 5), 10 (n = 3), and 25 (n = 3) mg/kg doses. The most common treatment-emergent adverse events were lymphocyte count decreased (45.5%), white blood cell count decreased (36.4%), and hypokalemia (36.4%). No serious adverse events or dose-limiting toxicities occurred during the treatment period, and the MTD was determined at 25 mg/kg once every 3 weeks. Systemic exposure of HLX22 increased with escalating dose levels. No patients achieved a complete or partial response, and four (36.4%) had stable disease. The disease control rate and median progression-free survival were 36.4% (95% confidence interval [CI], 7.9-64.8) and 44.0 days (95% CI, 41.0-170.0), respectively. HLX22 was well tolerated in patients with advanced solid tumors overexpressing HER2 after failure of standard therapies. The study results support further investigation of HLX22 in combination with trastuzumab and chemotherapy.