Confirmatory phase 3 clinical trial results demonstrated equivalence between MYL-1402O and bevacizumab in terms of efficacy, safety, and immunogenicity in the first-line treatment of patients with stage IV metastatic, nonsquamous non–small-cell lung cancer (NSCLC).
As a confirmatory step in the stepwise characterization for demonstration of biosimilarity, a multicenter, randomized, double-blind phase 3 study was conducted to compare the efficacy and safety of the bevacizumab biosimilar MYL-1402O with bevacizumab reference in combination with chemotherapy as first-line therapy in patients with stage IV metastatic, nonsquamous non–small-cell lung cancer (NSCLC); the results of this study were reported at the European Society for Medical Oncology Virtual Congress 2020.
Eligible patients were randomized 1:1 to receive MYL-1402O or bevacizumab reference in combination with carboplatin + paclitaxel every 21 days for 6 cycles up to 18 weeks followed by MYL-1402O or bevacizumab reference monotherapy for 8 cycles up to an additional 24 weeks, for a total of 42 weeks. The primary end point was overall response rate (ORR) at 18 weeks; key secondary end points included progression-free survival (PFS), overall survival (OS), safety, and immunogenicity up to 42 weeks. The equivalence margins for ORR were evaluated per the prespecifications set by the US Food and Drug Administration (ratio of ORR: 90% confidence interval [CI], 0.73-1.36) and the European Medicines Agency (difference in ORR: 95% CI, ±12.5%).
A total of 671 patients were randomized; of these, 337 received MYL-1402O and 334 patients received bevacizumab reference. The efficacy analysis showed similar outcomes between the 2 treatment groups. Between-group comparisons showed the ratio of ORR was 0.96 (90% CI, 0.83-1.12) and the difference in ORR was –1.6 (95% CI, –9.0-5.9); equivalence between the groups was established, because the CIs were within the predefined equivalence margin. At week 42, the median PFS by independent review for the MYL-1402O group was 7.6 months (95% CI, 7.0-9.5) and 9.0 months (95% CI, 7.2-9.7) for the bevacizumab group (P = .0906), which was consistent with the PFS by investigator assessment. For both groups, median OS was not reached at 42 weeks; the OS rate was 70.0% in the MYL-1402O group and 75.4% in the bevacizumab reference group.
Safety profiles were similar between the MYL-1402O and bevacizumab reference groups, with comparable incidence of serious adverse events (17.6% vs 16.7%, respectively) and treatment-related adverse events leading to death (2.4% vs 1.5%, respectively). Immunogenicity profiles were similar between the 2 groups, with 6.5% of patients developing antidrug antibodies in the MYL-1402O group compared with 4.8% of patients in the bevacizumab group.
These results demonstrated equivalence between MYL-1402O and bevacizumab reference in terms of efficacy, safety, and immunogenicity in patients with stage IV metastatic nonsquamous NSCLC.
Reference
Socinski MA, et al. ESMO 2020. Abstract 1391.