Abstract
Despite attempts, no HER2-directed therapies have been approved for gastric or gastroesophageal junction (GEJ) cancer after disease progression on trastuzumab. Trastuzumab deruxtecan (T-DXd, DS-8201) is a novel HER2-targeted antibody-drug conjugate composed of a humanized monoclonal antibody specifically targeting HER2, a cleavable tetrapeptide-based linker (drug-to-antibody ratio of ≈8), and a potent topoisomerase I inhibitor payload. In a phase 1 study, T-DXd (5.4 or 6.4 mg/kg) showed promising antitumor activity in a variety of tumor types, including a confirmed objective response rate (ORR) of 43% among patients with extensively pretreated HER2-positive gastric cancer (Shitara et al.
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