Publication

Abstract : Background: GP2013, a rituximab biosimilar, has been developed according to biosimilar development guidelines, with clinical trials in rheumatoid arthritis and follicular lymphoma (FL). Methods: This confirmatory phase III, double-blind, randomized, controlled trial compared efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of GP2013-CVP versus rituximab-CVP (R-CVP) in previously untreated, advanced-stage FL. The primary endpoint was equivalence in overall response rate (ORR), defined by 95% confidence interval [CI] with a margin of ± 12%. Secondary, non-powered endpoints comprised progression-free and overall survival, PK, PD, and safety. Patients were stratified by region and FLIPI risk score and randomized (1:1) to 8 cycles of GP2013-CVP (n = 314) or R-CVP (n = 315), followed by monotherapy maintenance for up to 2 years in responders (ClinicalTrials.gov identifier: NCT01419665). Results: The primary endpoint, equivalence of ORR between treatments, was met (GP2013-CVP: 87.1%; R-CVP: 87.5%; difference [95%CI] –0.40% [–5.94%, 5.14%]). Subgroup analyses suggested that ORR was similar between GP2013-CVP and R-CVP regardless of age (<, ≥60 years), gender, race, geographic region or bulky disease. Subgroup analyses reported numerical treatment differences (95%CI) of –8.41 (–17.09, 0.28) and 5.74 (–1.70, 13.17) for patients with FLIPI score of 0–2 and 3–5, respectively. Safety data from an interim analysis with an additional year of follow up showed that the pattern and rates of AEs (combination period: GP2013-CVP, 92.9%; R-CVP, 91.4%; maintenance period: GP2013, 72.0%; R, 69.4%) and SAEs (combination period: GP2013-CVP, 22.8%; R-CVP, 20.0%; maintenance period: GP2013 7.9%; R, 7.1%) are similar between treatments. Conclusions: The study demonstrated equivalence in ORR between the biosimilar GP2013 and reference rituximab in patients with previously untreated, advanced FL. Similarity in ORR was observed across subgroups and safety profiles were also comparable. Based on the totality of evidence, GP2013 was approved by the EMA and represents an important option for patients that need rituximab and to help sustain the cost of cancer care.