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)

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, pharmacokineti...

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Published in:BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2020-04, Vol.34 (2), p.171-181
Main Authors: Sharman, Jeff P., Liberati, Anna Marina, Ishizawa, Kenichi, Khan, Tahira, Robbins, Jeffery, Alcasid, Ann, Rosenberg, Julie Ann, Aurer, Igor
Format: Article
Language:English
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
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Description
Summary: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).
ISSN:1173-8804
1179-190X
DOI:10.1007/s40259-019-00398-7