Efficacy and safety of the proposed bevacizumab biosimilar BAT1706 compared with reference bevacizumab in patients with advanced nonsquamous non-small cell lung cancer: A randomized, double-blind, phase III study

Cancer Med. 2023 Nov;12(22):20847-20863. doi: 10.1002/cam4.6664. Epub 2023 Nov 7.

Abstract

Background: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements).

Results: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed.

Conclusion: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.

Keywords: bevacizumab; biosimilar; efficacy; nonsquamous non-small cell lung cancer; safety.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab / adverse effects
  • Biosimilar Pharmaceuticals* / adverse effects
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Double-Blind Method
  • Humans
  • Lung Neoplasms* / drug therapy
  • Paclitaxel / therapeutic use

Substances

  • Bevacizumab
  • Biosimilar Pharmaceuticals
  • Carboplatin
  • Paclitaxel

Grants and funding