A phase 2, multicenter, open-label study of trastuzumab deruxtecan (DS-8201a) in subjects with HER2-positive, unresectable and/or metastatic breast cancer previously treated with T-DM1.

TPS1102Background: There is no standard of care for HER2-positive breast cancer refractory to T-DM1. DS-8201a is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable peptide-based linker (deruxtecan), and with a high drug-to-antibody ratio of 7 to 8. In the ongoing phase 1 DS8201-A-J101 trial, DS-8201a showed a manageable safety profile and promising antitumor activity in HER2-positive breast cancer subjects previously receiving T-DM1 (confirmed objective response rate [ORR] of 61.4%; Oct 2017 data cutoff) (Modi et al, SABCS 2017). In August 2017, the FDA granted breakthrough therapy and fast track designations. Methods: The phase 2, open-label, multicenter, 2-part, DESTINY-Breast01 study will assess the efficacy and safety of DS-8201a in subjects with HER2-positive (confirmed by centralized testing) unresectable and/or metastatic breast cancer previously treated with T-DM1. Part 1 will enroll 120 subjects and includes ...