Dose-escalation and dose-expansion study of trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2+ gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03.

作者：Yelena Y. Janjigian, Do‐Youn Oh, Sun Young Rha, Keun Wook Lee, Neeltje Steeghs, Yee Chao, Maria Di Bartolomeo, M. Díez García, Nadia Haj Mohammad, Alexander Stein, William McAdoo, Megan Winter, Liz Croydon, Jeeyun Lee · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.4_suppl.295 · 被引用次数：44 · 研究领域：Gastric Cancer Management and Outcomes、HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research

295 Background: T-DXd is an antibody-drug conjugate composed of a humanized anti-HER2 monoclonal antibody, a tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. T-DXd is approved for HER2+ advanced/metastatic GC/GEJA after a prior trastuzumab-based regimen (US/Israel) and GC after chemotherapy (Japan). In DESTINY-Gastric01, T-DXd showed improved efficacy vs standard chemotherapy in Japanese and Korean pts (≥2 prior therapies) with advanced HER2+ GC/GEJA. Preclinical data of T-DXd combinations suggest encouraging antitumor activity. DESTINY-Gastric03 is the first study of T-DXd combinations in GC/GEJA. Methods: DESTINY-Gastric03 (NCT04379596) is a 2-part, phase 1b/2, multicenter, open-label, 3+3 dose-escalation (part 1) and -expansion (part 2) study in advanced/metastatic HER2+ GC/GEJA. In part 1, pts with locally confirmed HER2+ GC/GEJA (IHC 3+ or IHC 2+/ISH+) who progressed on/after ≥1 prior therapy including a trastuzumab-containing regimen received T-DXd intravenously (IV) every 3 weeks + assigned combination. Primary objectives were safety and recommended phase 2 dose (RP2D). Preliminary antitumor activity was a secondary objective; confirmed objective response rate (ORR) was a secondary endpoint. We report the T-DXd + fluoropyrimidine cohorts. Results: In part 1, 15 pts were assigned to T-DXd + IV 5-fluorouracil (5-FU) and 10 pts to T-DXd + oral capecitabine (Cap). In addition to trastuzumab, all pts had received prior treatment with 5-FU and/or...