Results of a multicenter double-blind phase I clinical trial of using of BCD-022 compared with Herceptin, used in combination with paclitaxel in patients with metastatic breast cancer

Within the framework of multicenter double-blind randomized clinical trial studied pharmacokinetics and safety of BCD-022 (trastuzumab, "Biocad" company, Russia), compared with the drug Herceptin (trastuzumab, F. Hoffmann-La Roche Ltd., Switzerland). Evaluation of the effectiveness was not the aim of the interim analysis, the results of which are shown. BCD-022 and Herceptin were used in combination with paclitaxel in patients with metastatic breast cancer with HER2 overexpressing (HER2 (+), mBC).

Methods. The analysis included 46 patients with HER2 (+) metastatic breast cancer (mBC) at the age of 29 to 71 years (22 - in the group of studied drug BCD-022 and 24 - in the Herceptin group). All patients received one course of therapy of BCD-022 or Herceptin 8 mg/kg intravenously and paclitaxel 175 mg/m2 intravenously on day 1 of a three-week course of treatment and continue to receive treatment with the same scheme with the use of trastuzumab 6 mg/kg (mandatory in the study is to conduct 6 courses of therapy). Randomization was carried out in groups in a ratio of 1: 1. The primary endpoint of pharmacokinetics evaluation was the area under the curve "concentration-time» (AUC0-504) of trastuzumab after a single application, the secondary - Cmax, T1 / 2 and Tmax. Safety was assessed based on the incidence of adverse events after the first course of therapy.

Results. Haematological toxicity, myalgia and arthralgia were the most frequent adverse events. Most reported adverse events had mild to moderate grade according to CTCA 4.03 and were caused  by effect of myelosuppressive chemotherapy. There were no statistically significant differences in adverse events frequency between the groups. There were 6 serious adverse events: 2 - in the BCD-022 group and 4 - in the Herceptin group. All pharmacokinetic parameters, including the primary endpoint (AUC 0-504) and secondary endpoints (Cmax, T1 / 2 and Tmax), of studied drug BCD-022 and Herceptin had no statistically significant difference.

Conclusion. BCD-022 (trastuzumab, "Biocad" company, Russia) regarding to its safety profile and pharmacokinetic properties is fully consistent with the original drug trastuzumab Herceptin (F. Hoffmann-La Roche Ltd., Switzerland) and can be recommended for further clinical study.

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