KEY TAKEAWAYS
- The DG-06 phase 2 trial aimed to evaluate T-DXd’s efficacy in HER2+ GC/GEJA pts from Japan/ South Korea.
- The primary endpoint was to assess ORR.
- The result demonstrated that T-DXd in Chinese HER2+ advanced GC/GEJA offers durable responses and manageable safety, consistent with DG01 findings.
Patients (pts) in China facing HER2-positive advanced or recurrent gastric cancer/gastroesophageal junction adenocarcinoma (GC/GEJA) encounter restricted treatment choices. However, Trastuzumab deruxtecan (T-DXd), being a HER2-targeted antibody-drug conjugate with a dose of 6.4 mg/kg, has gained approval for the treatment of adults with locally advanced or metastatic GC/GEJA in the United States, European Union, Japan, South Korea, and Singapore for pts who have previously undergone a trastuzumab-based regimen.
In the DG01 trial, Zhi Peng and his research group aimed to investigate the efficacy and safety of T-DXd at 6.4 mg/kg in Chinese patients with HER2-positive advanced or recurrent GC/GEJA, given the limited treatment options. The study assessed response rates and overall survival (OS), drawing from the significant improvements observed in similar patients from Japan/South Korea in the DESTINY-Gastric01 trial.
This interventional, open-label, single-arm study included Chinese pts with advanced GC/GEJA and HER2+ (defined as immunohistochemistry [IHC] 3+ or IHC 2+ with in situ hybridization [ISH] positivity as determined by a central laboratory). These pts had undergone at least two prior treatment regimens, including a fluoropyrimidine and a platinum agent. The intervention involved the administration of T-DXd at a dose of 6.4 mg/kg via intravenous infusion once every 3 weeks.
The primary endpoint was the confirmed objective response rate (ORR) assessed by independent central review (ICR) according to RECIST v1.1. Secondary endpoints encompassed the investigator-assessed (INV) demonstrated ORR, INV duration of response (DOR), INV progression-free survival (PFS), and OS. Safety and tolerability were also evaluated in the trial.
About 95 pts were enrolled in the study according to the intent-to-treat (ITT) criteria. Of these, 73 pts were confirmed as HER2-positive(IHC 3+ or IHC 2+/ISH+; full analysis set [FAS]) determined by a central laboratory. In the FAS, 65.8% of pts were below the age of 65, 72.6% exhibited IHC 3+, and the primary tumor location was in the GEJ for 30.1% of pts.
The study concluded that the initial analysis of T-DXd in Chinese pts with HER2-positive advanced GC/GEJA showcased substantial and enduring objective responses that hold clinical significance. The safety profile observed was manageable, aligning with findings from the DG01 trial.
This study is sponsored by AstraZeneca.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT04989816
Shen L, Chen P, Lu J, et al. “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”. Presented at ESMO Asia 2023. (Abstract: 172P).
