Pharmacokinetics and safety of IBI301 versus rituximab in patients with CD20+ B-cell lymphoma: a multicenter, randomized, double-blind, parallel-controlled study

Abstract

This multicenter, randomized, double-blind, parallel-controlled trial aimed to compare the pharmacokinetics (PK) of IBI301 with rituximab in patients with CD20-positive (CD20 + ) B-cell lymphoma, who achieved a complete response/unconfirmed complete response after standard treatments. Patients were randomized (1:1) to receive IBI301 or rituximab (375 mg/m 2 , IV). Patients who continuously benefitted from the trial after the PK phase underwent the extension phase to receive up to three cycles of 3-month-cycle of rituximab/IBI301 maintenance therapy. PK was described using the area under the serum concentration–time curve from time zero to infinity (AUC 0-inf ), AUC from time zero to last quantifiable concentration (AUC 0-t ), and maximum serum concentration ( C max ). Pharmacodynamics (PD), incidence of adverse events and immunogenicity were evaluated. PK was defined equivalent, if 90% confidence intervals (CIs) for geometric mean ratios of PK endpoints fell within the margin of 0.8–1.25. Overall, 181 patients were enrolled in IBI301 ( n = 89) and rituximab ( n = 92) groups. Geometric mean ratios of AUC 0-inf , AUC 0-t , and C max were 0.91 (90% CI 0.85, 0.97), 0.91 (90% CI 0.86, 0.97), and 0.96 (90% CI 0.92, 1.01) between treatment groups, all within the bioequivalence range. Peripheral CD19 + and CD20 + B-cell counts were similar at each prespecified time point between the groups. No difference in immunogenicity was observed. The incidences of treatment-emergent adverse events (84.3% vs. 83.5%) and treatment-related AEs (56.2% vs. 61.5%) were comparable (IBI301 vs. rituximab). IBI301 was PK bioequivalent to rituximab in patients with CD20 + B-cell lymphoma. The PD, safety, and immunogenicity profiles of IBI301 were similar to those of rituximab.

Safety and efficacy comparisons of rituximab biosimilars to the reference product in patients with cancer: a systematic meta‐analysis review

“…Twenty‐nine studies 13,15–21,25,26,28–30,32,34–37,39–47 reporting on RCTs were identified and included in the analysis, with 26 studies reporting efficacy outcomes (Table 2). Among all included studies, two reported on ABP 798, 17,18 two reported on BCD‐020, 28,41 eight reported on CT‐P10, 16,26,29–31,36,37,39,40 two reported on DRL‐Rituximab, 42,46 two studies reported on GP2013, 34,35 three reported on HLX01, 20,43,44 three reported on IBI301, 15,21,38 one reported on PF‐05280586, 19 two reported on RTXM83, 13,32,33 one reported on SAIT101, 25 and one reported on Zytux 45 (Table 2). All studies reported on treatment naïve patients, except for one study that reported on a single switch 16 …”

“…Most patients were treated for FL or DLBCL, and all patients besides those in one study 16 reported on patients who were treatment naïve. Figure 4a — forest plot — summarises results from 10 studies 15,19–21,25,26,30,33,34,41 involving 3066 patients (biosimilar n = 1528, reference n = 1538). Comparable incidence of patients experiencing at least one TEAE with the biosimilar of rituximab was similar to the reference (OR 1.20, 95% CI: 0.98–1.49, p = 0.08).…”

“…Twenty-nine studies 13,[15][16][17][18][19][20][21]25,26,[28][29][30]32,[34][35][36][37][39][40][41][42][43][44][45][46][47] reporting on RCTs were identified and included in the analysis, with 26 studies reporting efficacy outcomes (Table 2). Among all included studies, two reported on ABP 798, 17,18 two reported on BCD-020, 28,41 eight reported on CT-P10, 16,26,[29][30][31]36,37,39,40 two reported on DRL-Rituximab, 42,46 two studies reported on GP2013, 34,35 three reported on HLX01, 20,43,44 three reported on IBI301, 15,…”

“…Of 29 studies included for rituximab, seven studies also involved treatment with cyclophosphamide, vincristine, and prednisolone (CVP), 26,[29][30][31][34][35][36][37] nine studies involved treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), 13,20,21,32,33,38,[42][43][44]46 and 10 studies involved rituximab monotherapy [15][16][17][18][19]25,28,[39][40][41] (Table 2). One study involved rituximab as part of fludarabine, cyclophosphamide, and rituximab (FCR) treatment.…”

“…12 A 2019 systematic review and metaanalysis by Lee et al 14 involved both rheumatoid arthritis patients and NHL patients; however, more evidence has emerged since then which is specifically relevant to the oncology setting. [15][16][17][18][19][20][21]…”