A phase II, multicenter, open-label study of [fam-] trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing gastric cancer.

TPS180Background: There is no HER2-targeted therapy for patients with HER2-positive gastric cancer (GC) who progressed on trastuzumab-based therapy. [fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody, topoisomerase I inhibitor payload, cleavable peptide-based linker, and high drug-to-antibody ratio of approximately 8. In an ongoing phase I trial, [fam-] trastuzumab deruxtecan showed an acceptable safety profile and promising antitumor activity in salvage-line subjects with HER2+ GC who previously received trastuzumab (confirmed objective response rate [ORR] of 43.2% [19/44]; Iwata et al, ASCO 2018). Methods: The randomized, phase II, multicenter, open-label, DESTINY-Gastric01 study will assess the efficacy and safety of [fam-] trastuzumab deruxtecan in HER2-expressing GC. The primary cohort, HER2+ (IHC 3+ or IHC 2+/ISH+) GC subjects who progressed after ≥ 2 prior regimens and previously received trastuzumab, will be randomized (2:1) to ...