Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: Results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC.

8057 Background: BCD-021 demonstrated equivalence to Avastin in a comprehensive comparability exercise that included physicochemical, PK and PD studies, as well as phase I PK clinical study in patients with non-squamous NSCLC. Methods: 138 patients with advanced non-squamous NSCLC (stage IIIb/IV) 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 up to 6 cycles of therapy or until progression or unbearable toxicity. Results: ORR (primary endpoint) in both groups had no statistically significant differences: 42.59 % (95% CI 30.33 – 55.83) in BCD-021 group and 39.29% (95% CI 27.58 – 52.27%) in Avastin group. The lower limit of 95% CI for ORR difference between the groups (-14.96%) did not exceed the non-inferiority margin, hence BCD-021 is non-inferior to Avastin. There were also no differences between the groups for all other efficacy parameters: CR (1.85% vs 1.79%), PR (40.74% vs 37.50%), stable disease (51.85% vs 51.79%) and progression rate (5.56% vs 8.93%) in BCD-021 and Avastin group, respectively. AEs profiles of BCD-021 and Avastin were equivalent. Rate of all observed AEs including severe AEs had no statistically significant difference between the groups. Most AEs were associated with chemotherapy : neutropenia (85.29% vs 78,7%), anemia (88.24% vs 84.85%), leukopenia (79.41% vs 75.76%), thrombocytopenia (69.12% vs 62.12%), hyperglycemia (61.76 vs 56.06), LDH increase (48.53 vs 37.88), ALP increase (35.29% vs 30.30), ALT increase (26.47% vs 28.79%), alopecia (30.88% vs 24,24%), etc. Reactions specific for bevacizumab included: arterial hypertension (26,47% vs 22,73%), weakness (17.65 vs 16.67), lung bleeding (5.88% vs 3.03%), proteinuria (2.94% vs 0%), GIT perforation (0% vs 1.52%) and VTE (0% vs 1.52%). Binding and neutralizing antibodies were transient and detected only in 1 patient in each group that indicated to low immunogenic potential of both drugs. Conclusions: BCD-021 demonstrated non-inferiority to Avastin in patients with NSCLC. Clinical trial information: NCT01763645.