Breakthrough Results in HER2+ Metastatic GEA: Ziihera® Shows Promising Outcomes
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) has announced significant findings from the Phase 3 HERIZON-GEA-01 trial, demonstrating that Ziihera® (zanidatamab-hrii) in combination with chemotherapy outperforms existing treatment options in patients with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). These results are set to be presented at the 2026 ASCO Gastrointestinal Cancers Symposium on January 8, 2026, in San Francisco.
Study Overview and Key Findings
The HERIZON-GEA-01 trial assessed the efficacy and safety of Ziihera, both alone and in combination with the PD-1 inhibitor Tevimbra® (tislelizumab), against trastuzumab plus chemotherapy. The findings reveal:
- Median Progression-Free Survival (PFS): Ziihera combinations demonstrated a 35% reduction in the risk of disease progression or death compared to trastuzumab, achieving a median PFS of over one year.
- Median Overall Survival (OS): Ziihera combined with tislelizumab resulted in a median OS of 26.4 months, marking the longest reported survival in a Phase 3 GEA trial, surpassing the control arm by more than seven months.
- Consistent Efficacy: Benefits were observed across major prespecified subgroups, including variations in geographic region and PD-L1 status.
Statements from Leading Researchers
"Reaching more than two years of median overall survival in a global Phase 3 trial for HER2+ metastatic GEA is truly unprecedented," stated Dr. Elena Elimova from the Princess Margaret Cancer Centre, underscoring the trial's noteworthy findings.
Dr. Geoffrey Ku from Memorial Sloan Kettering Cancer Center emphasized, "The HERIZON-GEA-01 study's results are practice-changing, suggesting that Ziihera, with or without tislelizumab, should become the new standard of care for patients with HER2+ first-line locally advanced unresectable or metastatic GEA."
Detailed Efficacy Summary
The following data summarizes the primary endpoints from the HERIZON-GEA-01 trial:
| Endpoint | Trastuzumab + Chemotherapy | Ziihera + Chemotherapy | Ziihera + Tislelizumab + Chemotherapy |
|---|---|---|---|
| Median PFS | 8.1 months | 12.4 months | 12.4 months |
| Median OS | 19.2 months | 24.4 months | 26.4 months |
| Objective Response Rate (ORR) | 65.7% | 69.6% | 70.7% |
| Median Duration of Response (DoR) | 8.3 months | 14.3 months | 20.7 months |
Safety Profile and Future Outlook
The safety profile of Ziihera with or without tislelizumab remained consistent with known effects of HER2-directed therapies. Key safety findings included:
- Grade ≥3 treatment-related adverse events were reported at 71.8% for Ziihera plus tislelizumab and 59% for Ziihera plus chemotherapy.
- Diarrhea emerged as the most common Grade ≥3 adverse event, yet treatment-related discontinuations remained low.
Rob Iannone, M.D., M.S.C.E., Chief Medical Officer of Jazz Pharmaceuticals, commented, "These results affirm Ziihera as the HER2-targeted agent-of-choice, fundamentally shaping first-line treatment options for patients with HER2+ metastatic GEA." The company plans to move forward with FDA submissions and further development of Ziihera in other HER2-driven tumors, including upcoming trials in HER2+ metastatic breast cancer.