129MO - Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive (HER2+) advanced gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric06 (DG-06) final analysis

Background

In China, pts with HER2+ advanced gastric/GEJA have limited treatment options. T-DXd is a HER2-directed antibody-drug conjugate approved (6.4 mg/kg) for advanced HER2+ gastric/GEJA in pts with a prior trastuzumab-based regimen. DG-06 primary results showed a clinically meaningful objective response rate (ORR) in Chinese pts with HER2+ advanced gastric/GEJA. We report the DG-06 final analysis.

Methods

In this open-label, single-arm, Phase II trial (NCT04989816), Chinese pts with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization–positive) advanced gastric/GEJA with ≥2 prior treatment regimens received T-DXd 6.4 mg/kg IV infusion Q3W. Primary endpoint: confirmed ORR by independent central review (ICR) per RECIST 1.1. Secondary endpoints included progression-free survival by ICR and investigator assessment, and overall survival (OS). Safety, tolerability, pharmacokinetics (PK), and immunogenicity were assessed.

Results

At data cutoff (Feb 28, 2024), 95 pts were enrolled (intent-to-treat). 73 pts were HER2+ (centrally confirmed; full analysis set); 22 pts were not centrally confirmed HER2+. Median follow-up duration was 10 months (range 6–17). Summary efficacy and safety data are in the table. Adverse events (AEs) were reported by all pts; most common Grade ≥3 AE (29/95; 31%) was anemia. In the PK set (n=95), at end of infusion for cycle 4, mean T-DXd and total anti-HER2 serum concentrations were 104 and 110 μg/mL, respectively. In the anti-drug antibody (ADA) set (n=86), treatment-emergent ADAs were reported in 2 pts; no neutralizing ADAs were seen. Table: 129MO

AE, adverse event; CI, confidence interval; G, grade; ICR, independent central review; INV, investigator assessed; m, median; mo, months; ORR, objective response rate, OS, overall survival; PFS, progression-free survival

Conclusions

DG-06 final results were consistent with the primary analysis with no new safety signals observed. T-DXd showed a clinically meaningful OS, with a consistent safety profile in HER2+ advanced gastric/GEJA. PK data were similar to previous studies, with T-DXd stable in circulation.

Clinical trial identification

NCT04989816.

Editorial acknowledgement

Under guidance of the authors, medical writing and editorial support were provided by Carmen Grimaldos, PhD, of Helios Medical Communications, part of Helios Global Group, and were funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca / Daiichi Sankyo.

Funding

This study is sponsored by AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).

Disclosure

L. Shen: Financial Interests, Personal, Advisory Board: MSD, BI, Servier, AZ, Transcenta Holding Limited; Financial Interests, Institutional, Funding: Beigene, Ltd.; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Roche, Innovent, Beigene, Ltd., NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.