A phase I study comparing the biosimilarity of the pharmacokinetics and safety of recombinant humanized anti-vascular endothelial growth factor monoclonal antibody injection with Avastin^® in healthy Chinese male subjects.

ABSTRACT:

Background

The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers.

Methods

A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC_0-t). Secondary endpoints included maximum observed serum concentration (C_max), AUC from 0 extrapolated to infinity (AUC_inf), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA).

Results

The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC_0-t, C_max and AUC_inf between the test group and reference group were 91.71%-103.18%, 95.72%-107.49% and 91.03%-103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%-125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar.

Conclusion

In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting.

Trial registration

Registered 08/10/2019, CTR20191923.

SUBMITTER: Li H 

PROVIDER: S-EPMC10223897 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature