1205 - A Phase III Study Comparing SB8, a Proposed Bevacizumab Biosimilar, and Reference Bevacizumab in Patients with Metastatic or Recurrent Non-squamous NSCLC

Background

SB8 is a proposed biosimilar of the reference bevacizumab (BEV). This study compared the efficacy, safety, pharmacokinetics (PK), and immunogenicity of SB8 to BEV in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC).

Methods

In this randomised, double-blind, multicentre study, patients were randomised (1:1) to receive SB8 or BEV with paclitaxel and carboplatin Q3W followed by SB8 or BEV maintenance therapy until disease progression, unacceptable toxicity, death, or 1 year from the randomisation of the last patient. The primary endpoint was the best overall response rate (ORR) by 24 weeks of chemotherapy; risk ratio was analyzed in the full analysis set (FAS) and risk difference was analyzed in the per-protocol set (PPS). Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety, PK, and immunogenicity.

Results

A total of 763 patients (SB8, n = 379; BEV, n = 384) were randomized. Baseline characteristics were balanced between SB8 and BEV. In the FAS, the best ORR was 47.6% in SB8 and 42.8% in BEV; the risk ratio was 1.11 and its 90% CI was [0.975, 1.269], which was within the pre-defined equivalence margin of [0.737, 1.357]. In the PPS, the best ORR was 50.1% in SB8 and 44.8% in BEV; the risk difference was 5.3% and its 95% CI was [−2.2%, 12.9%], of which the lower margin was contained within and the upper margin was outside the pre-defined equivalence margin of [−12.5%, 12.5%]. The secondary efficacy endpoints in the FAS were comparable between SB8 vs BEV: median PFS (8.50 vs 7.90 months), median OS (14.90 vs 15.80 months), and median DOR (5.60 vs 5.85 months). The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between SB8 vs BEV (92.1% vs 91.1%). The most frequently occurring TEAEs were alopecia, anaemia, and nausea. PK parameters (C_trough and C_max) and the incidence of overall anti-drug antibodies (16.1% vs 11.0%) were comparable between SB8 vs BEV.

Conclusions

This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio. Other efficacy endpoints, safety, PK, and immunogenicity were comparable between SB8 and BEV.

Clinical trial identification

NCT02754882.

Editorial acknowledgement

Legal entity responsible for the study

Samsung Bioepis Co., Ltd.

Funding

Samsung Bioepis Co., Ltd.

Disclosure

M. Reck: Honoraria (self), Advisory / Consultancy: Samsung Bioepis Co., Ltd.; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche. J. Choi: Full / Part-time employment: Samsung Bioepis Co., Ltd. D. Shin: Full / Part-time employment: Samsung Bioepis Co., Ltd. All other authors have declared no conflicts of interest.