Jazz Pharmaceuticals plc (NASDAQ:JAZZ) reported positive efficacy and safety findings from the Phase 3 HERIZON-GEA-01 clinical trial investigating Ziihera (zanidatamab-hrii) in patients diagnosed with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). This cancer type encompasses malignant tumors originating in the stomach, gastroesophageal junction, or esophagus.
The HERIZON-GEA-01 trial, a Phase 3 randomized study, assesses the impact of Ziihera combined with chemotherapy either with or without BeOne Medicines Inc.’s programmed death-1 (PD-1) inhibitor Tevimbra (tislelizumab) as an initial treatment approach. Jazz Pharmaceuticals collaborates on the development with partners Zymeworks Inc. (NASDAQ:ZYME) and BeOne Medicines Inc. (NASDAQ:ONC). Earlier topline results from this study were announced in November 2025, with more detailed data disclosed on Tuesday.
Data from the trial reveals that both investigated regimens — the doublet of Ziihera plus chemotherapy and the triplet combining Ziihera, chemotherapy, and Tevimbra — delivered statistically significant and clinically meaningful improvements in progression-free survival (PFS). Specifically, the doublet therapy yielded a 35% improvement in PFS, while the triplet regimen provided an approximate 37% reduction in the risk of disease progression or death. This translated to a median progression-free survival exceeding one year, surpassing the control arm by over four months.
Moreover, the triplet therapy demonstrated a notable benefit in overall survival (OS), with patients exhibiting a median OS of more than two years (26.4 months). Jazz Pharmaceuticals highlighted that this marks the longest median overall survival ever reported in a Phase 3 trial for gastroesophageal adenocarcinoma. This outcome represents over a seven-month improvement in median OS and corresponds to a 28% reduction in the risk of death compared with trastuzumab plus chemotherapy, the established comparator.
At the initial interim analysis, the doublet therapy also showed encouraging results, with median OS exceeding two years (24.4 months) and a strong trend towards statistical significance favoring Ziihera plus chemotherapy compared to trastuzumab plus chemotherapy. While the reduction in risk of death with the doublet regimen was approximately 20%, the analysis did not achieve formal statistical significance, with a p-value of 0.0564. Jazz Pharmaceuticals plans an additional interim OS analysis for the doublet therapy expected around mid-2026 to further elucidate outcomes.
Elena Elimova of the Princess Margaret Cancer Centre commented on these findings, stating that achieving a median overall survival exceeding two years in a global Phase 3 trial for HER2-positive metastatic gastroesophageal adenocarcinoma is unprecedented.
Following the announcement, Jazz Pharmaceuticals’ shares experienced a price increase of approximately 2.07%, trading at $170.44 at the time of publication, based on Benzinga Pro data.
Key Points:
- The Phase 3 HERIZON-GEA-01 trial evaluated Ziihera combined with chemotherapy, with or without Tevimbra, as a first-line treatment for HER2-positive metastatic gastroesophageal adenocarcinoma.
- Both dual and triple therapy regimens significantly extended progression-free survival, with median PFS surpassing one year and risk reductions of 35% (doublet) and 37% (triplet).
- The triplet therapy demonstrated a median overall survival exceeding two years, the longest recorded in a Phase 3 GEA trial, with a 28% reduction in mortality risk compared to trastuzumab plus chemotherapy.
- The doublet therapy showed promising overall survival results with a median exceeding 24 months and a trend towards statistical significance, anticipated to be further evaluated in an upcoming interim analysis in 2026.
Risks and Uncertainties:
- The doublet therapy's overall survival benefit, while encouraging, did not achieve conventional statistical significance at the first interim analysis, leaving some uncertainty regarding its definitive efficacy.
- Additional data from a planned mid-2026 interim analysis are necessary to confirm the durability of the observed survival benefits.
- Safety profiles and long-term tolerability outcomes, although mentioned, were not detailed in the announcement, which could impact clinical application and adoption.
- Market reaction and stock performance remain subject to broader industry trends and regulatory decisions beyond trial data.
Disclosure: This article is for informational purposes only and does not constitute investment advice. All data are based solely on the trial results and corporate announcements as reported.