A pharmacokinetic study to comparatively evaluate the bioequivalence and safety of a humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 with the reference Herceptin in healthy Chinese subjects

Purpose. This study aimed to compare the safety, tolerability, pharmacokinetics (PK), and bioequivalence of a test humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 (HER-2) with the reference Herceptin (R). Materials and methods. The trial consisted of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, where 16 healthy subjects were either intravenously infused with QLHER2 (test) at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4, and 6 mg/kg) or given 4 mg/kg Herceptin (reference) for evaluating the safety, tolerability, and PK of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects. Results. Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) in part I, C-max and T-max were 19.43-120.01 mu g/mL and 68.91-157.87 h, respectively. AUC(0-t) and CL were 1.91-34.21 h center dot mu g/mL and 0.54-0.12 mL/h/kg, indicating lower clearance at higher doses, with a greater than proportional increase in AUC(0-t) and t(1/2) of 68.91-157.87 h. In part II, serum concentrations were comparable between QLHER2 and Herceptin over a 70-day sampling period, and the QLHER2/Herceptin ratios of C-max and AUC(0-t) were 105.90% [90% confidence interval (CI): 95.69%-117.26%] and 95.79% (90% CI: 87.74%-106.40%), respectively. Conclusion. The 90% CI value of C-max and AUC(0-t) for QLHER2/Herceptin ratio ranged between 80.0%-125.00%, indicating that QLHER2 was bioequivalent to Herceptin. These results support further evaluation of QLHER2. Trial registration number: ChiCTR2000041577 and ChiCTR2100041802. Date of registration: 30th December, 2020 and 5th January 2021.