NYU Langone Health, New York, NY, 10016, USA.
Imperial College and Imperial College Healthcare NHS Trust, London, UK.
Cancer Chemother Pharmacol. 2018 Mar;81(3):505-514. doi: 10.1007/s00280-017-3510-7. Epub 2018 Jan 12.
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.
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); AUC from time 0 to last quantifiable concentration (AUC); and observed maximum serum concentration (C). The pre-determined equivalence criterion was a 90% confidence interval of 80-125% for ratios of geometric least squares (LS) means.
Equivalence of CT-P6 and reference trastuzumab was demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90% confidence interval) were: AUC 99.05 (93.00, 105.51); AUC 99.30 (92.85, 106.20); C 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.
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.
曲妥珠单抗是一种有价值的抗癌治疗药物，但由于其费用较高，其应用可能会受到限制。本研究的主要目的是评估和比较 CT-P6（曲妥珠单抗的一种生物类似药）与美国许可的参考药物（赫赛汀）在健康受试者中的药代动力学特征。次要研究目的包括比较 CT-P6 和参考药物在这些受试者中的安全性和免疫原性。
我们进行了一项单剂量、随机、双盲、平行组研究（NCT02665637），比较了 CT-P6（6mg/kg，90 分钟静脉输注）与参考药物（6mg/kg，90 分钟静脉输注）在 70 名健康成年男性中的作用。在给药后 10 周内评估药代动力学、安全性和免疫原性。主要终点是从 0 时到无穷大（AUC）的血清浓度-时间曲线下面积（AUC）；从 0 时到最后可量化浓度（AUC）的 AUC；以及观察到的最大血清浓度（C）。预先确定的等效标准是几何最小二乘（LS）均值比值的 90%置信区间为 80-125%。
证明 CT-P6 与参考药物等效。几何 LS 均值（90%置信区间）的比值为：AUC99.05（93.00，105.51）；AUC99.30（92.85，106.20）；C96.58（90.93，102.59）。安全性特征相似；CT-P6 组有 10 名（28.6%）受试者和参考药物组有 11 名（31.4%）受试者出现治疗后出现的不良事件。没有发生严重不良事件或死亡。没有受试者检测到抗药物抗体呈阳性。
这些数据增加了证明生物相似性所需的总体证据。一项 CT-P6 的 III 期研究已经证明其与参考药物的新辅助疗效等效，目前正在进行中。
