A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL)

• Published in: BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy Vol. 34; no. 2; pp. 171 - 181
• Main Authors: Sharman, Jeff P., Liberati, Anna Marina, Ishizawa, Kenichi, Khan, Tahira, Robbins, Jeffery, Alcasid, Ann, Rosenberg, Julie Ann, Aurer, Igor
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2020; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Autoimmune diseases; Biological products; Biomedical and Life Sciences; Biomedicine; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - pharmacokinetics; Biosimilar Pharmaceuticals - pharmacology; Biosimilar Pharmaceuticals - therapeutic use; Cancer Research; CD20 antigen; Chemotherapy; Double-Blind Method; Double-blind studies; Drug dosages; FDA approval; Female; Humans; Immunogenicity; Immunoglobulins; Immunotherapy; Internet resources; Lymphoma; Lymphoma, Follicular - drug therapy; Male; Middle Aged; Molecular Medicine; Monoclonal antibodies; Oncology; Original; Original Research Article; Pharmacodynamics; Pharmacokinetics; Pharmacotherapy; Regulatory approval; Rituximab; Rituximab - adverse effects; Rituximab - pharmacokinetics; Rituximab - pharmacology; Rituximab - therapeutic use; Safety; Studies; Targeted cancer therapy; Therapeutic Equivalency; United States > US
• ISSN: 1173-8804; 1179-190X; 1179-190X
• DOI: 10.1007/s40259-019-00398-7

Background Biosimilars are highly similar to the licensed biologic (“reference product”), with no clinically meaningful differences in safety, purity, or potency between the two products. Objective This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera ® ; rituximab-EU). Patients and Methods Subjects with CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) and an Eastern Cooperative Oncology Group performance status 0–1 were randomized (1:1) to PF-05280586 or rituximab-EU (375 mg/m 2 intravenously [once weekly for 4 weeks at days 1, 8, 15, and 22]), stratified using the Follicular Lymphoma International Prognostic Index 2 classification. The primary endpoint was overall response rate (ORR) at week 26 (percentage of subjects achieving complete response [CR] or partial response [PR]). Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the difference in ORR between groups was within the prespecified margin (± 16%). Secondary endpoints included progression-free survival (PFS), CR rate, safety, immunogenicity, PK, and PD. Results A total of 394 subjects were randomized: PF-05280586 ( n  = 196) or rituximab-EU ( n  = 198). ORR at week 26 was 75.5% (PF-05280586) versus 70.7% (rituximab-EU), for a difference of 4.66%; 95% CI (− 4.16 to 13.47), which was entirely within the prespecified equivalence margin. Rates of CR were 29.3% (PF-05280586) versus 31.0% (rituximab-EU). Estimated 1-year PFS rates were 78.2% (95% CI 70.2–84.2) and 83.0% (95% CI 75.0–88.6) for PF-05280586 and rituximab-EU, respectively. Safety, immunogenicity, and mean serum concentrations were similar between groups. Conclusions The efficacy, safety, immunogenicity, PK, and PD of PF-05280586 and rituximab-EU were similar up to week 52 in subjects with previously untreated CD20-positive LTB-FL. Clinical Trial Registration ClinicalTrials.gov, NCT02213263 and EudraCT (2014-000132-41).