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.
Resources from the same session
529P - Ramucirumab plus docetaxel after combination chemoimmunotherapy in patients with non-small cell lung cancer: A prospective observational study
Presenter: Tadaaki Yamada
Session: Poster Display
Resources:
Abstract
530P - MYC recruits tumor-associated macrophage to sustain metastatic malignancy of lung adenocarcinoma micropapillary subtype through epigenetic reprogramming
Presenter: Xuming Song
Session: Poster Display
Resources:
Abstract
531P - Effect of combinational targeted therapy for AXL and ATR against malignant mesothelioma cells
Presenter: Soichi Hirai
Session: Poster Display
Resources:
Abstract
532P - The changes of the serum SMRP levels is useful to predict the antitumor efficacy of ipilimumab plus nivolumab combination therapy in patients with malignant pleural mesothelioma
Presenter: Taiichiro Otsuki
Session: Poster Display
Resources:
Abstract
533P - Efficacy in the elderly NSCLC patients in SCORPION study: Phase II study of DTX plus RAM following platinum-based chemotherapy plus ICIs
Presenter: Teppei Yamaguchi
Session: Poster Display
Resources:
Abstract
534P - DSC2 promotes the proliferation, metastasis and drug resistance of lung cancer by activating the PI3K/AKT pathway
Presenter: Qi Li
Session: Poster Display
Resources:
Abstract
535P - Alteration in NKX2-1 CN reshapes the oncogenic, immunologic, and prognostic landscapes in NSCLC
Presenter: Herdee Gloriane Luna
Session: Poster Display
Resources:
Abstract
536P - The evaluation and long-term outcome of pulmonary metastasectomy for osteosarcoma: A 20-year experience of Shanghai Rujin Hospital
Presenter: Zhusheng Zhang
Session: Poster Display
Resources:
Abstract
537P - The impact of treatment-free interval on patient outcome after pulmonary metastasectomy for sarcoma
Presenter: Po-Kuei Hsu
Session: Poster Display
Resources:
Abstract
538P - First-line chemoimmunotherapy for metastatic thymic carcinoma
Presenter: Victoria Andreas
Session: Poster Display
Resources:
Abstract