Abstract 172P
Background
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.
Methods
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.
Results
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.
Conclusions
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: 172P
| FAS | N=73 |
| Median 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) |
| ITT | N=95 |
| Median 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) |
| G1 | 2 (2.1) |
| G2 | 1 (1.1) |
| G3–G5 | 0 |
Clinical trial identification
NCT04989816.
Editorial acknowledgement
Under the guidance of the authors and in accordance with Good Publications Practice (GPP), medical writing and editorial support was provided by Robyn Wood, MSc, of Helios Medical Communications, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca, Daiichi Sankyo Daiichi Sankyo.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.
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