Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01.

作者：Elena Elimova, Sun Young Rha, Kohei Shitara, Tianshu Liu, Josep Tabernero, Keun-Wook Lee, Michael Schenker, N. C. Tebbutt, J. A. AJANI, N. Salimin, Geoffrey Y. Ku, Jong Gwang Kim, Inmaculada Alés Díaz, Jingdong Zhang, Filippo Pietrantonio, Li-Yuan Bai, Samuel Le Sourd, Ye Chen, Jonathan E. Grim, Lin Shen, on behalf of the HERIZON-GEA-01 study group · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.2_suppl.lba285 · 被引用次数：11 · 研究领域：Cancer Immunotherapy and Biomarkers、HER2/EGFR in Cancer Research、Esophageal Cancer Research and Treatment

LBA285 Background: HERIZON-GEA-01 (NCT05152147) is a global, open-label, phase 3 trial of zanidatamab (dual HER2-targeted bispecific antibody) + CT ± tislelizumab (anti–PD-1) vs trastuzumab (tras) + CT in 1L HER2+ mGEA. Methods: Eligible patients (pts) with previously untreated HER2+ mGEA, regardless of PD-L1 status, were randomized (1:1:1) to zanidatamab (1800 mg [<70 kg] / 2400 mg [≥70 kg] IV Q3W) + tislelizumab (200 mg IV Q3W) + capecitabine/oxaliplatin (CAPOX) or 5-FU/cisplatin (FP); zanidatamab + CAPOX or FP; or tras + CAPOX or FP. Dual primary endpoints were progression-free survival (PFS) by blinded independent central review and overall survival (OS). Results: 914 pts were randomized (Dec 2021 to Feb 2025). Demographics and baseline disease characteristics were balanced. At data cutoff (Oct 2025), median follow-up was 26 mo. Compared with tras + CT, PFS was significantly prolonged in zanidatamab-containing arms (Table). A statistically significant OS benefit was observed with zanidatamab + tislelizumab + CT (Table). OS for zanidatamab + CT was not significant at the first interim analysis, although a strong trend favoring zanidatamab + CT was observed. Improvements in PFS and OS occurred across major subgroups, including by region and PD-L1 TAP score. Grade ≥3 treatment-related AEs (TRAEs) occurred in 71.8% of pts with zanidatamab + tislelizumab + CT, 59.0% with zanidatamab + CT, and 59.6% with tras + CT. Grade ≥3 TRAEs occurring in >10% of pts in either zanidat...