TX05-03e: Adjuvant treatment following neoadjuvant treatment and surgical resection in TX05-03, a trial comparing the safety, efficacy, and immunogenicity of trastuzumab biosimilar candidate (TX05) with originator trastuzumab in HER2+ EBC.

Abstract

LBA511 Background: TX05 is being developed as a biosimilar to trastuzumab. We previously reported results of a Phase III study (TX05-03) comparing the efficacy and safety of TX05 to originator trastuzumab (TRA) in patients with HER2+ early breast cancer (EBC). The rate of pathologic complete response for subjects treated with TX05 compared to TRA in the TX05-03 study were within pre-defined equivalence margins, supporting the therapeutic equivalence of TX05 and TRA. This is an extension study to further assess and characterize the safety, immunogenicity, and efficacy of TX05 and TRA as single agents. Methods: TX05-03e was a randomized double-blinded, parallel group Phase III trial with patients enrolled at 82 centers in 10 countries. Adjuvant treatment included single agent trastuzumab (TX05 or TRA) for up to thirteen 3-week cycles. Subjects originally assigned to TX05 in the neoadjuvant phase of treatment received TX05, while subjects randomized to TRA in the neoadjuvant phase were randomized (1:1) to receive either TX05 or TRA. Efficacy endpoints include assessment of disease-free survival and overall survival. DFS is defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) to the documentation of a first failure. OS is defined as the time from randomization in the neoadjuvant study until death from any cause. Safety parameters assessed include treatment emergent adverse events (TEAE) and serious adverse events (SAE), death, clinical laboratory parameters, vital signs, 12-Lead ECG, LVEF and Physical examination. Immunogenicity was also assessed. Results: Of the 338 subjects randomized, 256 received TX05 while 82 received TRA. 81 of the TX05 patients received TRA in the neoadjuvant treatment phase. Demographic and baseline characteristics were well balanced between the three arms (TX05/TX05, TRA/TRA, or TRA/TX05 in neoadjuvant/adjuvant treatment phases). There was one death reported (TRA/TX05 group due to disease progression). DFS events occurred in only 3.4% of the TX05/TX05 group, 6.1% of the TRA/TRA group and 3.7% of the TRA/TX05 group. The number of subjects with any AE was 53.1% in the TX05/TX05, 56.1% in the TRA/TRA group and 37% in the TRA/TX05 groups. Frequency, type and severity of adverse events related to study drug were similar between the three groups and no new safety signals were detected. Conclusions: The rates of DFS, OS, AEs and immunogenicity were comparable in subjects randomized to TX05/TX05, TRA/TRA or TRA/TX05 for neoadjuvant/adjuvant treatment and continue to support the conclusion of biosimilarity of TX05 to the reference product. The change from TRA to TX05 for adjuvant treatment has no detectable impact on safety or treatment outcome. Clinical trial information: NCT04109391.