Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts.

Abstract

2501Background: DS-8201a is a HER2-targeted antibody drug conjugate with novel topoisomerase I inhibitor payload and linker technology. Methods: This ongoing phase 1 study (NCT02564900) enrolls subjects (sbj) with HER2+ breast cancer (BC) post T-DM1, HER2+ gastric cancer (GC) post trastuzumab, HER2 low BC (IHC 1+ or 2+, ISH-), and other HER2-expressing solid tumors (IHC ≥1+). Results: [Results will be updated for presentation at meeting] From Sep 2015–Dec 2017, 212 sbj received ≥1 dose of DS-8201a; 200 at 5.4 or 6.4 mg/kg. Median (mdn) age was 59 y with mdn of 4 prior regimens. At data cutoff, 121/200 (60.5%) sbj remain on treatment (tx). Mdn duration of tx was 10.3 mo (range 0.7+, 21.2+ mo). Overall, RECIST-confirmed overall response rate (ORR) in the evaluable sbj was 81/160 (50.6%) with the highest ORR in HER2+ BC (64.2%). Mdn duration of response was not reached (NR, range 0.03+, 15.2+ mo). 155/181 (85.6%) of sbj with ≥1 postbaseline scan (ps) experienced tumor shrinkage (92.3% of them at 1st ps at 6 ...