A randomized Phase I pharmacokinetic trial comparing the potential biosimilar trastuzumab (SIBP-01) with the reference product (Herceptin®) in healthy Chinese male volunteers

ABSTRACT

Objectives

This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin®.

Methods

In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg•kg–1 intravenous dose of SIBP-01 or Herceptin®. Serum concentrationswere analyzed using a validated ELISA.

Results

The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of C_max, AUC_0-t and AUC_inf between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC_0-t and AUC_inf in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin®. AEs were similar across all subjects in the SIBP-01 and Herceptin® arms, with treatment-related AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study.

Expert opinion

Trastuzumab (Herceptin®) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin®is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin®, with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin® in healthy subjects and cancer patients 2.

Conclusions

This study showed the PK similarity of SIBP-01 to Herceptin®. SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity 4.

KEYWORDS:

• Trastuzumab
• SIBP-01
• bioequivalence
• pharmacokinetics
• phase I
• safety

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Z. H., D.L., and W.H. contributed to the conception and design. Z.H., C.S. and Z.X. conducted the analysis and interpretation of the data and participated in the drafting of the paper. X.J., G.Q., F.L., and W.Y. contributed to the management of drug and biological sample disposition. Z.J. contributed to quality control throughout the study. S.R. contributed to the study organization and implementation. S.Z. and L.B. participated in the sample collection. L.Y. provided medical supervision. All authors were involved in revising the paper critically for intellectual content and the final approval of the version to be published. All authors agree to be accountable for all aspects of the work.

Additional information

Funding

This trial was sponsored by the Shanghai Institute of Biological Products Co. Ltd., and this study was funded by  Natural Science Foundation of Anhui Province (2008085QH401).