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Phase I study of biosimilar trastuzumab demonstrates equivalent pharmacokinetics to reference product Posted 27/04/2018

Trastuzumab, a recombinant humanized monoclonal antibody, acts against the tyrosine kinase human epidermal growth factor receptor 2 (HER2), which is overexpressed in up to 30% of breast cancers and gastric cancers and has been linked to poor prognosis. In the age of targeted anticancer therapy, trastuzumab is a key treatment for patients with HER2-positive (HER2+) tumours and is recommended by a number of clinical guidelines. However, the use of ‘originator’ (or reference) biologicals, such as trastuzumab, is associated with high treatment costs; an issue set to be exacerbated by an ageing population. The improved cost-effectiveness potentially provided by a biosimilar may increase patient access to treatment.

The trastuzumab biosimilar, CT‑P6, is approved in Europe and South Korea for all indications of the reference product [1, 2] and is currently under review by the US Food and Drug Administration (FDA) [3]. Results of a phase I clinical study reported that CT‑P6 was pharmacokinetically (PK) equivalent to reference trastuzumab in healthy subjects, with a similar safety profile [4].

Subjects in the 10-week study (NCT02665637) were healthy adult male volunteers, and each received a single 6 mg/kg dose of either CT‑P6 or reference trastuzumab via intravenous infusion. The study was randomized 1:1 and conducted in a double-blind fashion. PK analysis was conducted on blood samples taken up to 10 weeks post‑dose and safety and immunogenicity were assessed throughout. Seventy subjects were randomized; 35 to each treatment group.

The study, according to the authors, demonstrated PK equivalence of CT‑P6 and reference trastuzumab according to predetermined criteria. Criteria were that the 90% confidence intervals for the geometric least squares mean ratios (CT‑P6/reference trastuzumab) of the primary PK endpoints (area under the serum concentration-time curve [AUC] from time 0 to infinity, AUC from time 0 to last quantifiable concentration, and observed maximum serum concentration) were between 80 and 125%. The study also found that secondary PK endpoints and overall PK profiles were comparable between treatment groups. Safety profiles were similar for both agents and no serious adverse events or deaths occurred. Immunogenicity was similar between treatment groups; no subjects tested positive for anti-drug antibodies.

These data form an important part of the stepwise collection of evidence required by regulatory authorities in Europe and the US for the assessment of biosimilarity. A phase III study of CT‑P6 in the neoadjuvant treatment of HER2+ early breast cancer (NCT02162667) further supports these data, with equivalent efficacy and a similar safety profile to reference trastuzumab demonstrated in this patient population.

Conflict of interest
The study was sponsored by Celltrion. Several of the authors of the research paper [4] reported conflicts of interest, including having served as a consultant for Celltrion, having received payment from Celltrion for conducting the study and being an employee of Celltrion.

For full details of the authors’ conflict of interest, see the research paper [4].

Abstracted by Francisco J Esteva, NYU Langone Health, New York, USA (medical writing support provided by Hannah Mace at Aspire Scientific and funded by Celltrion).

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1. GaBI Online - Generics and Biosimilars Initiative. Biosimilar trastuzumab approved in Korea [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Apr 27]. Available from: www.gabionline.net/Biosimilars/News/Biosimilar-trastuzumab-approved-in-Korea
2. GaBI Online - Generics and Biosimilars Initiative. EC approval for trastuzumab biosimilar Herzuma [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Apr 27]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-trastuzumab-biosimilar-Herzuma
3. GaBI Online - Generics and Biosimilars Initiative. Two trastuzumab biosimilars submitted to FDA [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Apr 27]. Available from: www.gabionline.net/Biosimilars/News/Two-trastuzumab-biosimilars-submitted-to-FDA
4. Esteva FJ, Stebbing J, Wood-Horrall RN, Winkle PJ, Lee SY, Lee SJ. A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab. Cancer Chemother Pharmacol. 2018;81(3):505-14.

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