Efficacy and safety of BCD-022, trastuzumab biosimilar candidate, compared to herceptin: Results of international multicenter randomized double blind study in patients with HER2+ mBC

Abstract

Background: BCD-022 demonstrated equivalence to Herceptin in a comprehensive comparability physicochemical, non-clinical PK and PD studies, as well as phase I PK clinical study in patients with HER2+ mBC. Methods: 126 patients with HER2-positive metastatic BC were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-022 or Herceptin at a loading dose of 8 mg/kg and then in maintenance dose of 6 mg/kg in combination with paclitaxel (175 mg/m2) 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: 53.57% (95% CI 40.70 - 65.98%) in BCD-022 group and 53.70% (95% CI 40.60 - 66.31%) in Herceptin group. The lower limit of 95% CI for ORR difference between the groups (-19.83%) did not exceed the non-inferiority margin, hence BCD-022 is non-inferior to Herceptin. There were also no differences between the groups for all other efficacy parameters: CR (5.36 vs 3.70%), PR (48.21 vs 50.00%), SD (25.00 vs 25.93%) and progression rate (21.43 vs 20.37%) in BCD-022 and Herceptin group, respectively. AEs profiles of BCD-022 and Herceptin 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 (73.02 vs 73,77%), anemia (82.54 vs 77.05%), leukopenia (73.02 vs 68.85%), lymphopenia (69.84 vs. 65.57%), thrombocytopenia (17.46 vs 29.51%), hyperglycemia (57.14 vs 70.49%), ALP increase (38.68 vs 42.62%), AST increase (42.86 vs 42.62%), ALT increase (33.33 vs 40.98%), alopecia (33.33 vs 34.43%), arthralgia (17.46 vs 18.03%) etc. Cardiovascular events specific for trastuzumab included: tachycardia (34.92 vs 19.67%), arterial hypertension (20.63 vs 18.03%), atrial fibrillation (0 vs 3.28%), extrasystoles (0% vs 1.64%), CAD gr.1 (1.59 vs 0%) and aggravated myocardiodystrophy (1.59 vs 0%). Binding antibodies with neutralizing activity were detected only in 1 patient in each group that indicated to low immunogenic potential of both drugs. Conclusions: BCD-022 demonstrated non-inferiority to Herceptin in patients with HER2+ mBC.