Jazz Pharmaceuticals plc announced positive top-line results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera(zanidatamab-hrii) in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra (tislelizumab), as first-line treatment for HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus. Both Ziihera plus chemotherapy and Ziihera plus tislelizumab and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared to the control arm, trastuzumab plus chemotherapy. Ziihera plus tislelizumab and chemotherapy also demonstrated clinically meaningful and statistically significant improvements in overall survival (OS), and Ziihera plus chemotherapy demonstrated a clinically meaningful effect with a strong trend toward statistical significance for OS compared to the control arm at the time of this first analysis.
The trial is ongoing with an additional planned OS interim analysis for Ziihera plus chemotherapy currently expected in mid-2026. A PFS and OS benefit was observed in the Ziihera plus tislelizumab and chemotherapy arm versus the control arm in both PD-L1 positive and PD-L1 negative subgroups. Both Ziihera plus chemotherapy, and Ziihera plus tislelizumab and chemotherapy demonstrated improvements in the key secondary endpoints of objective response rate (ORR) and duration of response (DoR) versus the control arm, and these endpoints were supportive of the primary efficacy endpoints.
The safety profile of Ziihera in combination with chemotherapy, with or without tislelizumab, was generally consistent with the known safety profile of each agent with no new safety signals observed in the two investigational combination arms and supports the overall benefit risk of Ziihera for use in this indication.Jazz plans to submit these data for presentation at a major medical meeting in the first quarter of 2026 and for publication in a peer-reviewed journal, and will rapidly submit for adoption in the National Comprehensive Cancer Network Guidelines (NCCN Guidelines).HERIZON-GEA-01 marks the first Phase 3 trial results for Ziihera. Ongoing research for Ziihera includes the Phase 3 HERIZON-BTC-302 trial evaluating Ziihera and CisGem (cisplatin plus gemcitabine) with or without the addition of a PD-1/L-1 inhibitor versus CisGem with or without a PD-1/L1 inhibitor in adult participants with HER2+ biliary tract cancer; the Phase 3 EmpowHER-303 trial evaluating Ziihera compared to trastuzumab, each in combination with physician's choice of chemotherapy, for the treatment of participants with metastatic HER2+ breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment; the DiscovHER PAN-206 basket trial evaluating Ziihera monotherapy in previously-treated patients with HER2+ (IHC 3+) cancers; and the Phase 2 EmpowHER-208 trial evaluating Ziihera in patients with HER2+ neoadjuvant and adjuvant breast cancer.
