Key Results of International Randomized Open-Label Clinical Study of BCD-020 (rituximab biosimilar candidate) in Patients with B-Cell Non-Hodgkin’s Lymphoma

Abstract

BCD-020 (Acellbia, rituximab biosimilar candidate) was shown to be highly similar to innovator rituximab (MabThera®/Rituxan®) in terms of its quality characteristics, in vitro biological activity, as well as toxicology and PK/PD characteristics in non-human primates. International multicenter comparative randomized open-label clinical study was carried out in a period from 2011 to 2013 and involved over 30 centers in Russia, Ukraine and India. Its methodology and design complies with current EMA guidelines on similar biological products containing monoclonal antibodies (EMA/CHMP/BMWP/403543/2010). 92 patients with follicular non-Hodgkin’s lymphoma, stage I-IV by Ann Arbor, or marginal zone lymphoma, stage I-IV by Ann Arbor, ECOG 0-2, who had at least 1 measurable lesion were enrolled. According to study protocol patients with secondary transformed B-cell lymphomas or with highly aggressive types of tumor, bulky disease, severe concomitant somatic disorders and some other conditions were excluded. If a patient had previous story of chemotherapy or radiation he could be included after at least 3 weeks post-treatment. Participation of patients who were previously treated with any kind of monoclonal antibodies was prohibited. After signing standard informed consent form and completion of 28-days screening period eligible patients underwent stratification in accordance to their prognostic risk (FLIPI or IPI) and previous treatment (naïve or pretreated). Subsequently patients were randomized (1:1) into 2 groups: 46 patients were included in the main group where Acellbia (rituximab biosimilar) was administered at a dose of 375 mg/m2 as a slow IV infusion on day 1, 8, 15 and 22; 46 patients were included in the reference group where MabThera was used at the same regimen. Use of any other medicines for the treatment of lymphoma was strictly prohibited. Efficacy was assessed on the basis of computed tomography and bone marrow evaluation which were performed 1 month after the completion of treatment. Median age of patients in each group was 57.5 years (main group [50.0-64.0], reference group [47.0-65.0]). Manageable comorbidities were reported in 50% of patients in the main group and 34.78% of patients in the reference group, p=0.2053. Comparative analysis of the prognostic risk factors confirmed the equivalence of study groups. The number of pretreated patients in both groups was equal – 8 individuals per group. Statistical analysis didn’t find any difference in overall response rate in general population of patients (39.52% patients in the main group vs. 36.57% patients in the reference group, p=0.8250), as well as in population of pretreated patients (28.6% vs 37.5% respectively, p=1.00) and in population of naïve patients (42.8% vs 39.4% respectively, p=1.00). The lower limit of the two-tailed 95% CI for difference in proportions of ORR was equal to -0.17 and exceeded the predefined non-inferiority margin -0.2, which confirmed non-inferiority of Acellbia to MabThera in terms of efficacy. Treatment-associated AE of any grade were reported in 21.74% patients in both arms, in the absence of statistically or clinically significant difference (p = 0.8005). There were 2 cases of CTCAE 4.03 grade 3-4 AEs in each group. PK and PD parameters were shown to be equivalent in both study groups. Thus, study results suggest that Acellbia has same efficacy and safety in patients with B-cell non-Hodgkin’s lymphoma. Disclosures Chernyaeva: JCS BIOCAD: Employment. Ivanov:JCS BIOCAD: Employment. Isaev:JCS BIOCAD: Employment.

Rituximab biosimilars for lymphoma in Europe

“…Limited published preclinical data are available; similarities between BCD-020 and reference rituximab in terms of quality characteristics, in vitro biological activity, toxicology, and PK/PD profiles in nonhuman primates have been demonstrated [113]. Phase III clinical testing was conducted in patients with FL or marginal zone lymphoma, and in rheumatoid arthritis [113,114]. Both studies showed comparable efficacy, PK/PD, and safety profiles for reference rituximab and BCD-020.…”

A clinician’s guide to biosimilars in oncology

“…Phase III: BCD-020 showed equivalent PK and similar PD and safety to rituximab in patients with indolent NHL [41] Phase III: BCD-020 showed similar efficacy (ORR) and safety to rituximab in patients with indolent B-cell non-Hodgkin's lymphoma [42] PF-05280586…”

Biosimilars: Implications for Clinical Practice

“…48 A randomized study of BCD-020 in 92 patients with follicular or marginal zone non-Hodgkin lymphoma reported no statistical difference in ORR between the biosimilar (40%) and rituximab (37%; P 5 .8250), and treatment-related adverse events also were similar between arms. 24 PK, safety, and immunogenicity data are available for the candidate rituximab biosimilar PF-05280586 in patients with rheumatoid arthritis, whereas PK immunogenicity data have been reported with RTXM83 in diffuse large B-cell lymphoma. [49][50][51] The candidate biosimilar BCD-021 demonstrated similar efficacy to the anti-vascular endothelial growth factor mAb bevacizumab in combination with paclitaxel plus carboplatin in a phase III trial in 138 patients with advanced nonsquamous non-small-cell lung cancer; the ORRs were 43% versus 39%.…”

“…More importantly, the patents for several mAbs with widespread use in the treatment of cancers, such as trastuzumab, bevacizumab, rituximab, and cetuximab, either have expired or will soon expire, and biosimilars for these biologics are in the late stages of clinical development (Table 2). [7][8][9][10][17][18][19][20][21][22][23][24][25][26][27] Thus, it is essential that physicians and others involved in the treatment of patients with cancer begin to learn about biosimilars, the efficacy and safety standards they are required to meet for regulatory approval, and how to effectively explain these new agents to patients.…”