Mechanism of action of the trastuzumab biosimilar CT-P6

ABSTRACT

Objectives: Therapeutic monoclonal antibody biosimilars are expected to help reduce the sizeable economic burden of targeted treatments. Trastuzumab (Herceptin®), a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2, is approved for use in HER2-overexpressing breast cancer (in both the adjuvant and metastatic settings) and HER2-positive gastric cancer. CT-P6 (Herzuma®) is a biosimilar of trastuzumab, designed to bind with high affinity and specificity to the same HER2 epitope as the reference product. We investigated whether CT-P6 exerts its effects through the same mechanism of action as trastuzumab.

Methods: The mechanism of action of CT-P6 and trastuzumab, both as monotherapy and in combination with paclitaxel or pertuzumab, was compared in HER2-overexpressing breast cancer and gastric cancer cell models.

Results: We confirmed that CT-P6 functions in a manner similar to trastuzumab by binding to the HER2 receptor, which is central to the effects of trastuzumab in all indications.

Conclusions: Collectively, the results of this study show that the mechanisms of action of CT-P6 and trastuzumab are similar in HER2-positive breast cancer and gastric cancer models and, therefore, CT-P6 can be expected to perform similarly in the clinical setting.

KEYWORDS:

• Biosimilar
• breast cancer
• CT-P6
• gastric cancer
• mechanism of action
• trastuzumab

Author Contributions

The corresponding author confirms that he had full access to the data in the study and final responsibility for the decision to submit for publication. SHK and SJC conceived the work. SAJ, JMC, JMP, SHK, and SJC designed the study. SAJ, JMP, JYL, SJL, SuYL, SiYL, YAP, HJJ, and YCS acquired the data. SAJ, JMC, SHK, and SJC interpreted the results. All authors drafted and/or critically revised the manuscript and approved the final draft for submission.

Declaration of interest

All authors are employees of Celltrion Inc., Incheon, Republic of Korea and own company stocks. Editorial support (including editing an advanced draft provided by the authors, finalizing tables and figures, and collating and incorporating final author comments on the edited draft) was provided by Rick Flemming PhD, CMPP at Aspire Scientific (Bollington, UK), and funded by Celltrion Healthcare Co., Ltd (Incheon, Republic of Korea). Rick Flemming is a director and shareholder of Aspire Scientific Limited, a company that receives payment for providing medical writing support to pharmaceutical and biotechnical companies, including Celltrion Healthcare Co., Ltd and Celltrion Inc. The authors have no other 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 apart from those disclosed.

Disclaimer

The views expressed herein are those of the authors alone and are made in a scientific capacity only. It should not be inferred that the authors, or Celltrion, Inc., are making any representations of a legal or regulatory nature. In particular, nothing in this article should be taken to promote, encourage, or endorse use of biosimilar trastuzumab in a manner that might be outside the scope of any authorized therapeutic indications or inside the scope of any valid intellectual property rights.

Reviewer Disclosures

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

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was funded by Celltrion Inc., Incheon, Republic of Korea.