A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab

Purpose Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin ® ) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects. Methods We performed a single-dose, randomised, double-blind, parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6 mg/kg, 90 min intravenous infusion) in 70 healthy adult males. Pharmacokinetics, safety and immunogenicity were evaluated up to 10 weeks post-dose. Primary endpoints were area under the serum concentration–time curve (AUC) from time 0 to infinity (AUC inf ); AUC from time 0 to last quantifiable concentration (AUC last ); and observed maximum serum concentration ( C max ). The pre-determined equivalence criterion was a 90% confidence interval of 80–125% for ratios of geometric least squares (LS) means. Results Equivalence of CT-P6 and reference trastuzumab was demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90% confidence interval) were: AUC inf 99.05 (93.00, 105.51); AUC last 99.30 (92.85, 106.20); C max 96.58 (90.93, 102.59). Safety profiles were similar; treatment-emergent adverse events occurred in ten subjects (28.6%) in the CT-P6 group and 11 (31.4%) in the reference trastuzumab group. No serious adverse events or deaths occurred. No subjects tested positive for anti-drug antibodies. Conclusions These data add to the totality of evidence required to demonstrate biosimilarity. A phase III study of CT-P6—in which equivalent neoadjuvant efficacy to reference trastuzumab has been demonstrated—is ongoing.