Abstract P5-20-13: Biosimilar ABP 980 in patients with early breast cancer: Results of single switch from trastuzumab to ABP 980
Authors: von Minckwitz G , Turdean M , Zhang N , Santi P , Hanes V 
Published: February 2018

Abstract
Background: Analytical, functional, and pharmacokinetic similarity between ABP 980 and trastuzumab (TRAS) has been demonstrated. Here we report results from the single switch treatment arm in the adjuvant phase of the corresponding clinical study.
Methods: The objective of this randomized, multicenter, double-blind study was to compare ABP 980 with TRAS in women with HER2-positive early breast cancer. After run-in anthracycline-based chemotherapy, patients were randomized 1:1 to intravenous ABP 980 or TRAS plus paclitaxel Q3W for 4 cycles. Surgery (breast and sentinel node or axillary lymph node dissection) was completed 3-7 weeks after the last dose of study drug. Following surgery, patients who initially received TRAS were allocated to either continue TRAS or undergo a single switch to receive ABP 980 Q3W for up to 1 year from the first dose of investigational product (IP) in the neoadjuvant phase. Allocation occurred at randomization and was maintained blinded. The objective of the single switch was to evaluate safety and immunogenicity of subjects transitioning from TRAS to ABP 980.
Results: Here we report data collected at the time of the primary analysis, when all patients had completed the first post-surgery clinical visit or withdrawn from the study. The majority of patients had completed the study at the time of this analysis. Of the 827 enrolled patients, 725 were randomized (ABP 980: n=364; TRAS: n=361). Of the 361 patients randomized to TRAS in the neoadjuvant phase, 173 and 174 patients in the TRAS/TRAS and TRAS/980 arm completed surgery, respectively, and 171 patients in each group entered the adjuvant phase following surgery. A total of 89 (52.0%) and 98 (57.3%) patients had an adverse event (AE) in the TRAS/TRAS and TRAS/980 group, respectively; 10 (5.8%) patients in each group had a grade ≥3 AE. AEs of interest are listed in Table 1.
Table 1: Adverse Events of Interest TRAS/980 (n = 171)TRAS/TRAS (n = 171) Total, n (%)Grade ≥3, n (%)Total, n (%)Grade ≥3, n (%)Any AE of interest45 (26.3)5 (2.9)39 (22.8)5 (2.9)Infections and Infestations21 (12.3)2 (1.2)14 (8.2)2 (1.2)Neutropenia13 (7.6)1 (0.6)16 (9.4)2 (1.2)Infusion reactions15 (8.8)3 (1.7)10 (5.8)1 (0.6)Hypersensitivity7 (4.1)03 (1.8)0Pulmonary toxicity1 (0.6)1 (0.6)2 (1.2)1 (0.6)Cardiac failure1 (0.6)01 (0.6)0
One patient in the TRAS/980 arm developed binding, non-neutralizing anti-drug antibodies (ADAs) during the adjuvant phase, compared with 4 patients (2 each in the ABP 980 and TRAS arms) in the neoadjuvant phase. The percentage of patients with disease progression or recurrence or death was 5.3% and 2.9% in the TRAS/TRAS and TRAS/980 arm, respectively (hazard ratio for TRAS/980 vs TRAS/TRAS, 0.48; 90% CI: [0.181, 1.292]).
Conclusions: Switching from TRAS to ABP 980 following surgery was safe in patients with breast cancer. Switching did not increase the frequency or severity of AEs and no unexpected safety signals were noted, and it did not increase the incidence of developing ADAs. Event-free survival was also similar between treatment groups.
Citation Format: von Minckwitz G, Turdean M, Zhang N, Santi P, Hanes V. Biosimilar ABP 980 in patients with early breast cancer: Results of single switch from trastuzumab to ABP 980 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-13.