Efficacy and Safety of BP02 (Trastuzumab Biosimilar) in HER2-Positive Metastatic Breast Cancer: A Multicenter Phase III Study

Abstract

Background and objective: Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02, a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as a trastuzumab biosimilar. The objective of this study was to evaluate the equivalence of BP02 with reference trastuzumab (RT: Herceptin^®-EU) in patients with HER2-positive metastatic breast cancer.

Methods: This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75 mg/m² on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Results: Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ± 13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively.

Conclusions: BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks.

Clinical trial registration: CTRI Number: CTRI/2020/04/024456.

Fig. 1

Patient disposition. The study is ongoing, with a maintenance phase currently underway. AE adverse event, ITT intent-to-treat

Fig. 2

Forest plots of a risk difference and b risk ratio (intent-to-treat [ITT] and per protocol [PP] population) among patient subgroups at the end of the induction phase. CI confidence interval, ECOG Eastern Cooperative Oncology Group, ER estrogen receptor, PR progesterone receptor

Fig. 3

Kaplan–Meier plots of a progression-free survival and b overall survival (intent-to-treat population) at the end of the induction phase. Medians of progression-free survival and overall survival were not reached