1338P - A phase III study comparing BCD-021, a bevacizumab biosimilar, and reference bevacizumab in patients with stage IIIB or IV non-squamous NSCLC

Background

BCD-021 (JSC BIOCAD) is a biosimilar of the reference bevacizumab (Avastin®). This study compared the efficacy, safety, pharmacokinetics (PK), and immunogenicity of BCD-021 to BEV in patients with stage IIIB or IV non-squamous non-small cell lung cancer (NSCLC).

Methods

In this randomised, double-blind, multicentre study, patients were randomised in a ratio 1:1 (for Russia, Belarus and Ukraine) and 2:1 (for India) to receive BCD-021 or BEV with paclitaxel and carboplatin Q3W for 6 cycles. Patients with stable disease, complete or partial responses at Week 18 were offered BCD-021 until disease progression, death, or unacceptable toxicity. The primary efficacy endpoint was objective response rate (ORR) based on responses achieved by Week 19 and confirmed 4 weeks thereafter. Primary PK endpoint was AUC_(0-t) after first infusion. Secondary endpoints were safety, PK, and immunogenicity.

Results

A total of 357 patients were randomized and 341 patients (BCD-021, n=205; BEV, n=136) were treated and had at least 1 CT scan after initiation of study treatment (mITT population). Baseline characteristics were balanced between BCD-021 and BEV with the exception for race. In the, the ORR was 34.6% in BCD-021 and 33.8% in BEV; the risk difference was 0.8% and its 95% CI was [-9.5 %, 11.1 %]. The 90% CI for risk ratio was [79.6%, 131.7%]. CIs were within the pre-defined equivalence margins of [-18%, 18%] for risk difference and [67%, 150%] for risk ratio. Sensitivity analysis for ORR with race as covariate resulted in 90% CI for risk ratio [79.2%, 132.1%]. The 90% CIs for the ratios of geometric means of AUC_(0-t) values for BCD-021 and BEV were within the pre-defined equivalence margin of [80%, 125%] for Indian and non-Indian patient populations. The overall incidence of adverse events (AEs) was comparable between BCD-021 vs BEV (91.3% vs 93.4%). The most frequently occurring AEs were anaemia, neutropenia and alopecia. PK parameters (C_trough and C_max) and the incidence of anti-drug antibodies were comparable between BCD-021 and BEV.

Conclusions

This study demonstrated equivalence between BCD-021 and BEV in terms of ORR risk difference and risk ratio. Safety, PK, and immunogenicity parameters were comparable between BCD-021 and BEV.

Clinical trial identification

NCT01763645.

Editorial acknowledgement

Legal entity responsible for the study

JSC Biocad.

Funding

JSC Biocad.

Disclosure

D. Zhuravleva: Financial Interests, Institutional, Full or part-time Employment: Biocad. G. Voevodin: Non-Financial Interests, Institutional, Full or part-time Employment: Biocad. M. Shustova: Financial Interests, Institutional, Full or part-time Employment: Biocad. K.A. Kryukov: Financial Interests, Institutional, Full or part-time Employment: Biocad. V. Chistiakov: Financial Interests, Institutional, Full or part-time Employment: Biocad. All other authors have declared no conflicts of interest.