BACKGROUND AND OBJECTIVES: This phase III study (RI-01-006; FLINTER) was conducted to demonstrate equivalent efficacy of DRL_RI to EU-approved rituximab (MabThera®) in patients with previously untreated Stage II-IV, CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL). This study also evaluated safety, immunogenicity, rituximab concentrations, and pharmacodynamics (PD) of DRL_RI compared with MabThera. DESIGN AND METHODS: Previously untreated, stage II-IV, CD20-positive LTB-FL patients (N = 317) were randomized (1:1) to receive DRL_RI (n = 162) or MabThera (n = 155) as intravenous infusions of 375 mg/m² weekly for 4 weeks (induction period), and thereafter every 8 weeks from Week 12 to Week 36 (maintenance treatment), and followed up till Week 52. The primary end point was best overall response rate (BORR) up to Week 28 based on blinded independent central review. Efficacy equivalence was demonstrated if the two-sided 90% confidence interval (CI) for BORR difference was within the prespecified equivalence margin (±17%). Secondary end points included objective and complete responses, duration of response, progression-free survival, overall survival, safety, immunogenicity, mean serum concentrations, and PD. RESULTS: The BORR up to Week 28 was 80.2% versus 79.4% for DRL_RI versus MabThera group; with a difference of 0.89% (90% CI: -6.67 to 8.48; 95% CI: -8.05 to 9.93 within the prespecified margin). Both treatment groups were comparable for all secondary efficacy end points. Treatment-emergent adverse events were reported in 68.6% of patients; safety, immunogenicity, and mean serum concentrations were similar between groups. Peripheral B-cell counts declined below quantifiable limits in most patients, with a median time to B-cell depletion of 6.9 versus 7.0 days for DRL_RI versus MabThera. CONCLUSION: The study demonstrated efficacy equivalence of DRL_RI to MabThera; with comparable safety, immunogenicity, serum concentrations, and PD between groups. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov identifier: NCT03976102 and EudraCT (2018-004223-36).

Biologics Division Dr Reddy's Laboratories Ltd Bachupally Hyderabad Telangana 500090 India

Division of Hematology Department of Internal Medicine Yonsei University College of Medicine Severance Hospital Seodaemun gu Seoul Korea

Dr Reddy's Laboratories Ltd Hyderabad Telangana India

Fakultini Nemocnice Hradec Kralove 4 Interni Hematologicka Klinika Hradec Kralove Czech Republic

Hematología Clínica Unidad Funcional de Linfomas ICO Hospital Duran i Reynals Hospitalet Barcelona Spain

Minsk City Clinical Oncology Center Minsk Republic of Belarus

N N Alexandrov National Cancer Center Center of Belarus Minsk Region Republic of Belarus

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ClinicalTrials.gov
NCT03976102