Use of single-agent rituximab may provide a useful alternative to watchful waiting by delaying the time to initiation of chemotherapy in patients with low tumor burden follicular lymphoma (LTB-FL). However, access to biologics like rituximab can be restricted. Biosimilars to rituximab represent a potential opportunity to increase patient access and lower treatment cost. PF-05280586, a proposed biosimilar to rituximab, has the same primary amino acid sequence, similar physicochemical and in vitro functional properties, and demonstrated similarity to rituximab in nonclinical evaluations and a pharmacokinetics (PK) similarity trial in patients with active rheumatoid arthritis. This confirmatory trial will evaluate efficacy, safety, and immunogenicity of PF-05280586 and rituximab sourced from the EU (rituximab-EU) in patients with treatment-naïve CD20 + , LTB-FL in a monotherapy setting, which allows assessment of biosimilarity without potentially confounding factors such as chemotherapy.
Patients (N = 394) will be stratified by risk level and randomized (1:1; double-blind) to 4 weekly doses of IV PF-05280586 or rituximab-EU (375 mg/m2 of body surface area). The primary endpoint is overall response rate at Wk 26. Secondary endpoints include safety, time to treatment failure, progression-free survival, complete remission rate at Wk 26, response duration, overall survival, PK, CD19+ B-cell depletion, and immunogenicity. Eligible patients are ≥18 yrs with histologically confirmed, Grade 1-3a, low tumor burden, CD20+ follicular lymphoma with no elements of diffuse large B-cell lymphoma; Ann Arbor Stage II, III or IV; and ECOG status of 0-1. Key exclusion criteria are: patients who are not candidates for rituximab monotherapy; evidence of histologic transformation to high-grade or diffuse large B-cell lymphoma; central nervous system, meningeal involvement or cord compression by the lymphoma; ≥5000/mm3 circulating lymphoma cells; prior systemic therapy for lymphoma; prior treatment with rituximab; impaired bone marrow function; symptomatic ischemic heart disease or congestive heart failure; or active uncontrolled infection.
Clinical trial identification
Legal entity responsible for the study
I. Jacobs, B. Jin, D. Yin, L.A. Melia: Full time employee of and stock holdings and/or stock options from Pfizer Inc. M. Suster: is a consultant for Pfizer Inc.