Top-line results from the Phase 3 HERIZON-GEA-01 trial show that zanidatamab-based treatment combinations significantly improve outcomes for people with previously untreated HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma. The study compared zanidatamab plus chemotherapy and zanidatamab plus tislelizumab plus chemotherapy with the current standard treatment of trastuzumab plus chemotherapy.
Both zanidatamab regimens led to meaningful improvements in progression-free survival. The triplet combination with tislelizumab also produced a statistically significant overall survival benefit, while the doublet of zanidatamab plus chemotherapy showed a strong trend toward improved overall survival. Both investigational arms achieved higher response rates and longer response durations than the control group. These benefits were consistent regardless of a patient’s PD-L1 status.
The results suggest that zanidatamab-based combinations could become new first-line standards of care for HER2-positive metastatic gastroesophageal cancer, marking the first time a HER2-targeted therapy has outperformed trastuzumab in a Phase 3 trial in this setting. The safety profiles matched what has been previously known, with no new concerns identified.