Jazz Pharmaceuticals Announces Phase 3 Results for Ziihera

Jazz Pharmaceuticals (JAZZ) announced efficacy and safety results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra, as first-line treatment for adults with HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma, including cancers of the stomach, gastroesophageal junction and esophagus. The data will be presented as a late-breaking oral presentation at the 2026 ASCO Gastrointestinal Cancers Symposium in San Francisco on January 8, 2026 from 8:57- 9:07 a.m. PST. The study found: Both investigational arms, Ziihera plus tislelizumab and chemotherapy, and Ziihera plus chemotherapy, led to a statistically significant and clinically meaningful prolongation of progression-free survival with approximately 35% reduction in the risk of disease progression or death versus trastuzumab plus chemotherapy. This resulted in a median PFS of more than one year, representing a greater than four-month improvement compared to the control arm. Ziihera plus tislelizumab and chemotherapy demonstrated a statistically significant and clinically meaningful overall survival benefit with a median OS of more than two years, the longest reported in a Phase 3 trial in GEA, representing a greater than seven-month improvement in median OS and a 28% reduction in the risk of death versus trastuzumab plus chemotherapy. At this first interim analysis, Ziihera plus chemotherapy showed a median OS of more than two years, with a strong trend toward statistical significance, favoring Ziihera plus chemotherapy versus trastuzumab plus chemotherapy. An additional planned OS interim analysis for Ziihera plus chemotherapy is currently expected in mid-2026. The OS and PFS benefits were generally consistent across major prespecified subgroups including geographic region and PD-L1 status for both investigational arms. The safety profile of Ziihera in combination with chemotherapy, with or without tislelizumab, was consistent with the known effects of HER2-directed therapy and immunotherapy, and no new safety signals were identified. Duration of treatment was longest on the Ziihera plus tislelizumab and chemotherapy arm. Rates of Grade greater than or equal to3 treatment-related adverse events were 71.8% with Ziihera plus tislelizumab and chemotherapy, 59.0% with Ziihera plus chemotherapy, and 59.6% with trastuzumab plus chemotherapy. Discontinuations due to Ziihera- or trastuzumab-related and treatment discontinuations due to adverse events were 11.9% with Ziihera plus tislelizumab and chemotherapy, 8.5% with Ziihera plus chemotherapy, and 2.3% in the trastuzumab plus chemotherapy arm. The most common Grade greater than or equal to3 TRAE was diarrhea. Importantly, discontinuation of either Ziihera or trastuzumab due to treatment-related diarrhea was uncommon. Treatment-emergent diarrhea generally occurred early in treatment and resolved within three weeks. The manageable safety profile supports the feasibility of these combinations in the first-line metastatic setting. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed byJazzand BeOne (ONC) under license agreements from Zymeworks (ZYME), which first developed the molecule.