A randomized, double-blind, single-dose study to evaluate the biosimilarity of QL1101 with bevacizumab in healthy male subjects

Purpose This is the first study to compare the pharmacokinetics of QL1101, a proposed bevacizumab biosimilar, with Avastin ® sourced from Roche Diagnostics GmbH. Methods In this double-blind, single-dose, parallel-group study, healthy male subjects were randomized 1:1 to receive QL1101 or Avastin ® 3 mg/kg intravenously. Pharmacokinetic assessments were conducted for 85 days, with additional safety and immunogenicity assessments until day 90. Primary study endpoints were area under the concentration–time curve (AUC) from time zero to infinity (AUC 0–∞ ), AUC from time zero to the last quantifiable concentration (AUC 0–last ), and maximum serum concentration ( C max ). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the C 0–max , AUC 0–last , and AUC 0–∞ were within the predefined bioequivalence margin of 80–125.00%. Results A total of 82 subjects were randomized to the following groups: 42 to QL1101 and 40 to Avastin ® . The 90% CIs of the GMRs of AUC 0–∞ , AUC 0–last , and C max of QL1101 and Avastin® were (97.8%, 107.0%), (94.5%, 106.9%), and (94.1%, 107.3%), respectively, which were all within the bioequivalence margin. The incidence of adverse events was 90.5% and 95.0% in the QL1101 and Avastin® groups, respectively. Mean serum concentration–time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across the two treatment groups. Conclusions The study demonstrated the pharmacokinetic equivalence of QL1101 to Avastin ® . QL1101 (3 mg/kg, iv) is safe and tolerable in healthy Chinese subjects. These data support the further clinical evaluation of QL1101 as a bevacizumab biosimilar.