Phase 3 Trial of Rituximab Biosimilar Candidate GP2013 Shows Positive Results in Follicular Lymphoma

Primary results from the ASSIST-FL Phase 3, multinational, double-blind, randomized, controlled clinical trial of Novartis and Sandoz’s GP2013, a proposed biosimilar of rituximab (Roche’s Rituxan, MabThera), showed that GP2013 is a viable biosimilar candidate for patients with previously untreated advanced follicular lymphoma. Wojciech Jurczak, PhD, of the Department of Hematology, Jagiellonian University, Krakow, Poland, and colleagues published the results of their study in the June 29, 2017, issue of The Lancet Haematology. Reference rituximab is indicated to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis, and microscopic polyangiitis.

The study compared the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GP2013 plus cyclophosphamide, vincristine, and prednisone (GP2013-CVP)—consistent with clinical practice—with reference rituximab-CVP (R-CVP) in adults with previously untreated, advanced-stage follicular lymphoma of World Health Organization (WHO) histological grades 1, 2, or 3a. A total of 858 patients were screened for eligibility; 314 were randomly assigned GP2013, of whom 312 were eventually given GP2013, and 315 were assigned and given reference rituximab. Patients were recruited from 159 centers in 26 countries. Median follow-up was 11.6 months for the primary analysis. Patients received 8 cycles of the biosimilar GP2013-CVP or R-CVP (combination phase), followed by monotherapy maintenance for a 2-year period in those who responded to treatment.

The primary endpoint was comparability in overall response, with equivalence shown if the entire 95% confidence interval (CI) was within an equivalence margin of -12% to 12%. The primary endpoint was analyzed in patients who had received at least 1 (partial or complete) dose of the investigational treatment and who did not have any major protocol deviations. The primary endpoint was met: 271 of 311 patients (87%) receiving GP2013 and 274 of 313 patients (88%) receiving reference rituximab achieved an overall response. The 95% CI was within the pre-defined margin (range: -5.94 to 5.14).

The researchers reported that the occurrence of adverse events (AEs) and serious AEs was similar between the treatment groups: 289 of 312 patients (93%) in the GP2013-CVP group had an AE, and 71 of the 312 patients in the group (23%) had a serious AE. In the R-CVP group, 289 of 315 patients (91%) had an AE, and 63 of those patients (20%) had a serious AE. The most commonly reported AE was neutropenia (neutropenia was also the most common grade 3 or 4 AE during the combination and maintenance phases). The occurrence of anti-drug antibodies was similar between the 2 treatment groups (2% in the GP2013-CVP group, 1% in the R-CVP group).

Secondary endpoints of median progression-free survival and overall survival have not yet been reported, as the study is still blinded and data are evolving, according to Novartis. The final results of the ASSIST-FL study are expected in 2018 after the study has been completed. In addition to ASSIST-FL, Novartis and Sandoz’s GP2013 is being studied in a global development program that includes a comprehensive comparison of the biosimilar candidate and the reference product at the analytical, pre-clinical, and clinical levels. This includes a PK and PD study in RA (ASSIST-RA), an evaluation of the impact of transitioning from the reference product to the proposed biosimilar rituximab (ASSIST-RT). The development program also includes 5 preclinical studies.