Final analysis data from a confirmatory, randomized phase 3 study demonstrated clinical similarity between rituximab reference and its biosimilar ABP 798 in patients with CD20-positive non-Hodgkin lymphoma in terms of efficacy, safety, and immunogenicity.
The final analysis of the randomized, double-blind, active-controlled phase 3 study evaluating the efficacy, safety, and immunogenicity of ABP 798, a candidate biosimilar to rituximab, compared with rituximab reference in patients with CD20-positive non-Hodgkin lymphoma (NHL) was presented at the 2020 American Society of Clinical Oncology Annual Meeting.
Inclusion criteria included adult patients with histologically confirmed grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization, had asymptomatic low tumor burden, and had not received rituximab reference or rituximab biosimilar. Eligible patients were randomized to receive ABP 798 or rituximab reference, administered at a dose of 375 mg/m2 once weekly for 4 weeks, followed by week 12 and week 20. The primary end point was risk difference of overall response rate (ORR) by week 28 based on independent central blinded assessment; secondary end points included risk difference of ORR at week 12, pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity.
A total of 254 patients received ≥1 infusions of the drug; of these, 128 patients received ABP 798 and 126 patients received rituximab reference. In the overall study population, the median age was 58.5 years; the majority were white (79.3%). At screening, 24.6% of patients presented with Ann Arbor stage II, 46.5% of patients presented with stage III, and 28.9% with stage IV disease; 44.1% of patients were classified as low Follicular Lymphoma International Prognostic Index (FLIPI) risk, and 40.6% as intermediate FLIPI risk.
Efficacy results demonstrated no clinically meaningful differences between the 2 treatment groups. The primary end point of ORR by week 28 was comparable between the ABP 798 and rituximab reference groups (78% vs 70%); clinical equivalence was established between ABP 798 and rituximab reference based on the 2-sided 90% confidence interval of risk difference of ORR (–1.4%-16.8%) being within the prespecified margin (–15%-35.5%). PK analysis showed similarity in the geometric least squares means for serum concentrations over time between the 2 groups. In terms of PD, a similar proportion of patients in both groups achieved complete depletion of CD19+ cell count at day 8 (98.3% in both groups).
Overall, safety and immunogenicity profiles were similar between the 2 treatment groups, and were consistent with those previously reported for rituximab reference. The incidence of any adverse events (AEs) was 83.6% in the ABP group and 75.4% in the rituximab reference group; the incidence of grade ≥3 AEs was 10.9% and 10.3%, respectively, and serious AEs was 3.9% and 4.0%, respectively. In both groups, the most common AEs of any grade were headache, fatigue, and nausea; the most common AE of interest was infusion reactions.
In terms of immunogenicity, postbaseline incidence of binding antidrug antibodies was 2.4% in the ABP 798 group and 0.8% in the rituximab reference group; neutralizing antidrug antibodies were comparable between groups (0.8% in both groups).
Based on these results, it was concluded that clinical similarity between ABP 798 and rituximab reference was established in patients with CD20-positive NHL in terms of efficacy, safety, and immunogenicity.
Reference
Niederwieser D, et al. ASCO 2020. Abstract 8044.