A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults.

Objectives Recombinant human HER2 monoclonal antibody for injection (AK-HER2) is a potential biosimilar of trastuzumab (Herceptin (R)). This phase ROMAN NUMERAL ONE study aimed to demonstrate the pharmacokinetic (PK) equivalence between AK-HER2 and trastuzumab in healthy volunteers. Besides, safety and immunogenicity were investigated. Research design and methods This was a randomized, double-blind phase ROMAN NUMERAL ONE trial in 96 healthy adults who received a single intravenous infusion of AK-HER2 or trastuzumab at 6 mg/kg. The primary PK endpoints were area under the serum concentration curve (AUC) from time 0 to the last time point (AUC(0-t)) and peak concentration in serum (C-max). The PK bioequivalence was confirmed using the standard equivalence margins of 80%-125%. Results The PK profiles of AK-HER2 and trastuzumab displayed high similarity. The geometric mean ratios (90% confidence intervals) of primary PK endpoints were within 80%-125%. The C (max) and AUC (0-t) of female subjects in the AK-HER2 group were greater than those of male subjects (P <0.05). No infusion-related reactions (IRRs) or anti-drug antibody-positivity was observed after dosing. Conclusions AK-HER2 was demonstrated to have highly similar PK to trastuzumab in healthy Chinese adults. Both drugs showed comparable safety and immunogenicity using dexamethasone as premedication to prevent IRRs..