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)

Abstract

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).

Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in diffuse large B-cell lymphoma

“…Eight biosimilars of rituximab have been approved by a regulatory health authority with preclinical and clinical information. 69 – 82 From all these biosimilars, only four were approved after conducting a comparative trial in DLBCL patients.…”

Advances in targeted therapy for malignant lymphoma

“…35 The phase 3 study (NCT02213263) of PF-05280586 displayed positive results as well. 36 Moreover, ABP798 is currently under study (NCT02747043).…”

Current State and Comparison of the Clinical Development of Bevacizumab, Rituximab and Trastuzumab Biosimilars

“…Most manufacturers have designed clinical efficacy and safety comparisons between the candidate and the RMP in the setting of NHL. Sandoz (GP2013) chose to conduct its efficacy trial in combination with cyclophosphamide, vincristine, and prednisone in patients with advanced FL [53], whereas Pfizer (PF-05280586) performed it as a single agent in low tumor burden FL patients [55,90]. ABP798, the candidate of Amgen was evaluated in patients with grade I, II or IIIa FL and low tumor burden [49].…”