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Background BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). Methods Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. Results In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures. Conclusions Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. Trial registration The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).

e20593 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa polyethylene glycol (PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 (empegfilgrastim) is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. Methods: To compare efficacy and safety of filgrastim and BCD-017 at 3 mg and 6 mg doses an open-label, randomized, active-comparator, non-inferiority trial was conducted. 60 patients with histologically or cytologically confirmed breast cancer were randomly assigned to receive either subcutaneous (s.c.) injection of 3 mg BCD-017 (n=21), 6 mg BCD-017 (n = 20), or 5 mg/kg s.c. injections of filgrastim (n=19) administered daily until ANC ≥ 10x109 cells/L (maximum of 14 days) after chemotherapy (doxorubicin 60 mg/m2 and docetaxel 75 mg/m2) with stratification for weight and prior chemotherapy exposure. The primary efficacy endpoint was the incidence of severe neutropenia (ANC < 1.0x109 cells/L) during the first cycle of chemotherapy. Results: Incidence of severe neutropenia during the first chemotherapy cycle was 85,7%, 65,0% and 61,1% in BCD-017 3 mg, BCD-017 6 mg and filgrastim groups, respectively. Differences between BCD-017 groups and filgrastim group were not significant. Mean duration of grade 4 neutropenia in cycle 1 was 0,43, 0,40 and 0,33 days, accordingly (95% CI for difference between BCD-017 3 mg and filgrastim groups -0.22 to 0.41; 95% CI for difference between BCD-017 6 mg and filgrastim groups -0.25 to 0.38). Febrile neutropenia was observed only in BCD-017 3 mg and BCD-017 6 mg groups (one case in each group). A single administration of BCD-017 at the doses of 3 mg and 6 mg was as safe and well tolerated as standard daily filgrastim administration. There were no unexpected adverse events in all groups. Conclusions: The results of this study support comparable efficacy of single s.c. injection of 6 mg BCD-017 versus daily 5 mg/kg s.c. injections of filgrastim. Further phase III study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving chemotherapy is necessary. Clinical trial information: NCT01569087.

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