A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer

Abstract

Objectives: Efficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous non-small cell lung cancer. Methods: Patients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV 15 mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance monotherapy. The primary endpoint was best overall response rate (ORR) by 24 weeks. Secondary endpoints included survival outcomes, safety, PK, and immunogenicity. Results: 763 patients (SB8, n = 379; BEV, n = 384) were randomized; baseline characteristics were well balanced. Best ORR in the FAS was 47.6% and 42.8%, and best ORR in the PPS was 50.1% and 44.8% for SB8 and BEV, respectively. The risk ratio of best ORR was 1.11 (90% CI, 0.975−1.269), and the risk difference in best ORR was 5.3% (95% CI, −2.2%-12.9%). Median survival outcomes were comparable between SB8 and BEV: progression-free survival was 8.50 vs 7.90 months, respectively (HR [95% CI], 0.99 [0.83-1.18]; p = 0.9338); overall survival was 14.90 vs 15.80 months, respectively (HR [95% CI], 1.03 [0.83-1.28]; p = 0.7713); and duration of response was 7.70 vs 7.00 months, respectively (HR [95% CI], 1.05 [0.81-1.37]; p = 0.6928). Severity and incidence of treatment-emergent adverse events, PK, and immunogenicity were comparable between SB8 and BEV. Conclusion: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio, with comparable safety, PK, and immunogenicity.

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers

“…SB8 was well-tolerated and no safety concerns were identified. Consistently, no safety concerns were identified from Phase III study with SB8 in in patients with NSCLC, with administration of 15 mg/kg SB8 every 3 weeks for 24 weeks in combination with chemotherapy, followed by SB8 maintenance monotherapy [30]. Immunogenicity was comparable between all treatment groups and no NAbs were detected.…”

“…These results represent an important contribution to the totality of evidence for supporting the biosimilarity of SB8 to its reference product bevacizumab, following the demonstration of analytical and functional similarity in extensive quality and non-clinical assessments. This totality of evidence is complemented by further clinical data from a phase III study in patients with NSCLC, demonstrating equivalence of SB8 and bevacizumab in terms of best overall response rate and comparable safety, PK and immunogenicity [30]. AE adverse event, Bevacizumab-EU bevacizumab sourced from the European Union, Bevacizumab-US bevacizumab sourced from the United States, IP investigational product, PT preferred term, N number of participants in the Safety set, n number of subjects with that observation, SAE serious AE, TEAE treatment-emergent AE Percentages are based on the number of participants in the safety set.…”

“…These results represent an important contribution to the totality of evidence for supporting the biosimilarity of SB8 to its reference product bevacizumab, following the demonstration of analytical and functional similarity in extensive quality and non-clinical assessments. This totality of evidence is complemented by further clinical data from a phase III study in patients with NSCLC, demonstrating equivalence of SB8 and bevacizumab in terms of best overall response rate and comparable safety, PK and immunogenicity [ 30 ].…”

SB8: A Bevacizumab Biosimilar

“…SB8 has similar physiochemical characteristics and functional properties to those of reference bevacizumab (Table 3) [2,3]. In vitro functional assay data are supported by comparable anti-tumour activity of SB8 and reference bevacizumab in a human NSCLC xenograft mice model [2].…”

“…SB8 is approved in the EU for same types of cancer as bevacizumab (Table 2) [1]. SB8 has similar physicochemical, functional and pharmacodynamic characteristics to those of reference bevacizumab [2,3] and pharmacokinetic similarity of the agents has also been demonstrated [3,4]. This article summarizes, from an EU perspective, the key features of SB8 and its clinical use in the treatment of various cancers, focusing on non-small cell lung cancer (NSCLC).…”