Pharmacokinetics and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin in patients.

e13500 Background: BCD-021 is a bevacizumab biosimilar candidate manufactured by CJSC BIOCAD, Russia. Full spectrum of physicochemical and preclinical studies showed equivalence of BCD-021 to innovator drug Avastin. Methods: 28 patients with advanced non-squamous NSCLC (stage IIIb/IV) were enrolled in the study. Patients were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks. The primary endpoint was AUC(0-504), the secondary endpoints included Cmax, T1/2 è Tmax. Bevacizumab 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: Pharmacokinetic (PK) analysis demonstrated that 90% CI for ratio of geometric means of AUC(0-504) of bevacizumab after single BCD-021 and Avastin administration was 80.01–118.28%. This range was 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 secondary PK parameters. BCD-021 and Avastin were well tolerated without any significant differences in AEs frequency between the groups. The most common AEs included leukopenia and neutropenia. All other AEs (hyperglycemia, AST, ALT, ALP and LDH increase, arterial hypertension, alopecia, arthralgia, peripheral neuropathy, weakness etc.) 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-021 and Avastin after a single i.v. administration in patients with NSCLC 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: NCT01763645.