172P Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive locally advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary efficacy and safety from the phase II single-arm DESTINY-Gastric06 (DG06) trial

For pts with HER2-positive advanced/recurrent GC/GEJA in China, treatment options are limited. T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg is approved in the US, EU, Japan, South Korea and Singapore for treatment of locally advanced/metastatic GC/GEJA in adults who received a prior trastuzumab-based regimen. In DESTINY-Gastric01 (DG01), T-DXd showed significant improvements in response rates and overall survival (OS) versus standard therapies in pts from Japan/South Korea with HER2-positive advanced GC/GEJA. In this open-label, single-arm, phase 2 trial (NCT04989816), Chinese pts with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+ by central laboratory) advanced GC/GEJA who had received ≥2 prior treatment regimens, including a fluoropyrimidine and a platinum agent, received T-DXd 6.4 mg/kg intravenous infusion once every 3 weeks. Primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR) per RECIST v1.1. Secondary endpoints included investigator-assessed (INV) confirmed ORR, INV duration of response (DOR), INV progression-free survival (PFS), and OS. Safety and tolerability were assessed. At data cutoff (Jun 16, 2023), 95 pts were enrolled (intent-to-treat [ITT]); 73 pts were confirmed HER2-positive (IHC 3+ or IHC 2+/ISH+; full analysis set [FAS]) by central laboratory. In the FAS, 65.8% of pts were <65 years of age, 72.6% were IHC 3+ and primary tumor location in 30.1% of pts was GEJ. Efficacy and safety data are shown in table. This primary analysis of T-DXd in Chinese pts with HER2-positive advanced GC/GEJA demonstrated clinically meaningful and durable objective responses, with a manageable safety profile, and is consistent with results from DG01.Table: 172PFASN=73Median prior lines of therapy, n (range)2 (2–6)Median duration of follow-up, months (Q1, Q3)8.0 (6.0, 13.2)ICR confirmed ORR, n (%)21 (28.8)INV confirmed ORR, n (%)26 (35.6)Median DOR, months (95% confidence interval [CI])7.9 (4.6, 8.8)Median PFS, months (95% CI)5.7 (4.0, 6.8)Median OS, months (95% CI)10.2 (7.5, 14.3)ITTN=95Median T-DXd duration, months (range)3.4 (0.4,14.5)Grade (G) ≥3 adverse events (AE), n (%)70 (73.7)Discontinued treatment due to AEs, n (%)12 (12.6)Discontinued treatment due to COVID-19-associated AEs, n (%)5 (5.3)Adjudicated drug-related interstitial lung disease/pneumonitis, n (%)3 (3.2)G12 (2.1)G21 (1.1)G3–G50 Open table in a new tab