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Pharmacokinetics and safety of BCD-022, trastuzumab biosimilar candidate, compared to Herceptin in patients.
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2014
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Single Bcd-022Therapeutic Drug MonitoringTranslational MedicineOncologyMedicineBcd-022 StudyClinical TrialsClinical PharmacologyPharmacotherapyAnti-cancer AgentCancer TreatmentPharmacologyPharmacokineticsCancer ResearchPharmacodynamic ModelingTrastuzumab Biosimilar CandidateE11576 Background
e11576 Background: BCD-022 is a trastuzumab biosimilar candidate manufactured by CJSC BIOCAD, Russia. Full spectrum of physicochemical and preclinical studies showed equivalence of BCD-022 to innovator drug trastuzumab. Methods: 46 patients with HER2(+) mBC were enrolled in the study. Patients were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-022 or trastuzumab (a single loading dose 8 mg/kg a maintenance dose 6 mg/kg) with paclitaxel (175 mg/m2) every 3 weeks. The primary endpoint was AUC(0-504), the secondary endpoints included Cmax, T1/2 и Tmax. Trastuzumab serum concentrations were evaluated immediately before the first infusion and after 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h. Results: PK analysis demonstrated that 90% CI for ratio of geometric means of AUC(0-504) of trastuzumab after single BCD-022 and trastuzumab administration was 80.42–120.87%, for ratio of Cmax– 83.69–123.05%. These ranges were within pre-specified PK equivalence criteria of 80–125 % according to EMA recommendations (EMA/CHMP/BMWP/403543/2010). There were no statistically significant differences between the groups for all other PK secondary parameters. BCD-022 and trastuzumab were well tolerated without any significant differences in AEs frequency between the groups. The most common AEs included hematological toxicity (leukopenia, neutropenia and anemia), hyperglycemia, AST, ALT, ALP and LDH increase. Arterial hypertension, tachycardia, alopecia, myalgia and arthralgia were less frequent. The majority of AEs were of Grade 1-2 (CTCAE 4.03) and were associated with myelosuppressive chemotherapy. Conclusions: PK and safety characteristics of BCD-022 and trastuzumab after a single i.v. administration in patients with HER2(+) mBC are considered to be equivalent. These data allow continue BCD-022 study aimed to assess efficacy and safety in the same population. Clinical trial information: NCT01764022.