Trastuzumab deruxtecan in patients from China with previously treated human epidermal growth factor receptor 2–positive locally advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (DESTINY-Gastric06): results from a single-arm, multicenter, phase 2 trial

Background: Trastuzumab deruxtecan (T-DXd; 6·4 mg/kg) is approved for metastatic human epidermal growth factor receptor 2 (HER2)-positive (HER2+) gastric or gastroesophageal junction (GEJ) adenocarcinoma after a trastuzumab-based regimen. We report the final analysis of DESTINY-Gastric06, evaluating T-DXd in pretreated patients from China with advanced HER2+ gastric cancers (GC). Methods: The single-arm, multicenter, phase 2 DESTINY-Gastric06 trial (NCT04989816) enrolled patients from China with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+; locally documented) advanced gastric or GEJ adenocarcinoma with two or more prior treatments. Patients received T-DXd 6·4 mg/kg intravenous infusion every 3 weeks. The primary endpoint was confirmed objective response rate in HER2+ (IHC 3+ or IHC 2+/in situ hybridization-positive) tumors (full analysis set) by independent central review. Secondary endpoints included investigator-assessed confirmed objective response rate, progression-free survival by independent central review, overall survival, and safety. Findings: Of 126 patients screened between August 20, 2021, and December 7, 2022, 95 were enrolled (intent-to-treat; 73 patients had centrally confirmed HER2+ tumors). Median follow up was 10·2 months. Among the 73 patients, confirmed objective response rate (95% confidence interval) by independent central review was 28·8% (18·8-40·6%) and by investigator assessment was 37·0% (26·0-49·1%). Median progression-free survival by independent central review was 5·7 months. Median overall survival was 11·1 months. The most common Grade 1-2 adverse event was white blood cell count decreased (53·7%; 51/95). Interpretation: Consistent with other GC trials, T-DXd showed durable benefit, with no new safety signals, in pretreated patients from China with HER2+ advanced GC; data support T-DXd as a third- or later-line therapeutic option in this population. Funding: AstraZeneca.