The results of a phase 3, randomized, double-blind study established the equivalence of bevacizumab reference to its biosimilar BCD-021 in terms of clinical efficacy, safety, pharmacokinetics, and immunogenicity in patients with NSCLC.
A randomized, double-blind, multicenter phase 3 study compared the efficacy, safety, pharmacokinetics (PK), and immunogenicity of the bevacizumab biosimilar BCD-021 with bevacizumab reference product in patients with stage IIIB or IV nonsquamous non–small-cell lung cancer (NSCLC); the results of this study were reported at the 2021 European Society for Medical Oncology Annual Meeting.
Eligible patients were randomized in a 1:1 (for Russia, Belarus, and Ukraine) or 2:1 (for India) ratio to receive BCD-021 or bevacizumab reference in combination with chemotherapy (paclitaxel and carboplatin) every 3 weeks for 6 cycles. Patients with stable disease or complete or partial responses at week 18 were eligible to receive BCD-021 until disease progression, death, or unacceptable toxicity. The primary efficacy end point was objective response rate (ORR) at week 19 and confirmed 4 weeks thereafter. Secondary end points were safety, PK, and immunogenicity; the primary PK end point was area under the concentration-time curve from time 0 to time t after first infusion.
In patients in the modified intent-to-treat population who received treatment and had ≥1 computed tomography scans after study initiation, 205 of the 341 patients received BCD-021 and 136 patients received bevacizumab reference. ORRs were similar in the BCD-021 and bevacizumab reference groups (34.6% vs 33.8%), with a risk difference of 0.8% (95% confidence interval [CI], –9.5%-11.1%), which fell within the prespecified acceptance criteria of –12% to 12%. The 90% CI for risk ratio was 79.6% to 131.7%, which fell within the prespecified equivalence margins of 75% to 133.33%. Sensitivity analysis for ORR with race as a covariate resulted in 90% CI for risk ratio (79.2%-132.1%). In Indian and non-Indian patient populations, the 90% CIs for the ratios of geometric means of area under the concentration-time curve from time 0 to time t values for BCD-021 and bevacizumab reference were within the predefined acceptance criteria for equivalence after first infusion (80%-125%).
Overall, the incidence of adverse events was comparable in the BCD-021 and bevacizumab reference groups (91.3% vs 93.4%); the most common adverse events were anemia, neutropenia, and alopecia.
PK parameters (trough concentration and maximum serum concentration) were comparable between BCD-021 and bevacizumab reference. In terms of immunogenicity, the incidence of antidrug antibodies was comparable between BCD-021 and bevacizumab reference.
These study results demonstrated equivalence between BCD-021 and bevacizumab reference in terms of ORR risk difference and risk ratio, safety, PK, and immunogenicity parameters.
Source: Fadeeva N, Roy B, Nagarkar R, et al. A phase III study comparing BCD-021, a bevacizumab biosimilar, and reference bevacizumab in patients with stage IIIB or IV non-squamous NSCLC. Ann Oncol. 2021;32(suppl_5):S949-S1039.