The results of the randomized phase 3 TX05-03 study confirmed the therapeutic equivalence of trastuzumab reference and its biosimilar TX05 in terms of pathologic complete response, objective response rate, safety, and immunogenicity.
The results of a randomized phase 3 study (TX05-03) comparing the efficacy, safety, and immunogenicity of the trastuzumab biosimilar candidate TX05 with trastuzumab reference in patients with HER2-positive early breast cancer were presented at the 2021 European Society for Medical Oncology Annual Meeting.
In this randomized, double-blind, parallel-group, phase 3 trial, eligible patients were enrolled at 124 centers. Neoadjuvant therapy consisted of four 3-week cycles of chemotherapy (epirubicin and cyclophosphamide) followed by four 3-week cycles of TX05 or trastuzumab reference in combination with paclitaxel; surgery was performed 3 to 7 weeks thereafter. The primary study end point was pathologic complete response (pCR) in the per protocol population, which was defined as patients who received ≥1 doses of TX05 or trastuzumab, had no major protocol deviations impacting efficacy, and had an adequate surgical sample for pCR assessment. Equivalence was established if the 95% confidence interval of the risk ratio (TX05/trastuzumab reference) was contained within the prespecified margins (0.755, 1.325). Secondary end points were objective response rate (ORR), immunogenicity, and safety.
A total of 809 patients were randomized in the study. Of the 794 evaluable for efficacy, 404 received TX05 and 405 received trastuzumab reference. By independent central review, pCR rates were similar between the TX05 and trastuzumab reference groups (48.8% vs 45.3%). Equivalence was concluded based on pCR risk ratio of 1.0783 (95% confidence interval, 0.9185-1.2659), which was within the predefined equivalence margins. The ORR was also highly similar for TX05 and trastuzumab reference (84.3% vs 85.0%).
Safety analysis showed no differences between TX05 and trastuzumab reference in terms of frequency, type, and severity of adverse events. The safety profiles of the treatments were similar, with the most frequently reported adverse events including musculoskeletal and connective tissue disorders, nervous system disorders, and gastrointestinal disorders.
The results of the randomized phase 3 TX05-03 study confirmed the therapeutic equivalence of trastuzumab reference and its biosimilar TX05 in terms of pCR, ORR, safety, and immunogenicity.
Source: Krivorotko P, Manikhas A, Moiseenko F, et al. Trial comparing the safety, efficacy and immunogenicity of trastuzumab biosimilar candidate (TX05) with originator trastuzumab in HER2+ early breast cancer. Ann Oncol. 2021;32(suppl_5):S407-S446.
