Jazz Pharmaceuticals and BeOne Medicines reported updated phase 3 results showing estimated 36-month overall survival of 39.8% with a zanidatamab-based regimen, while a direct comparison did not establish a significant benefit from adding tislelizumab.
The ESMO Congress presentation took place in Madrid on Oct. 23. The HERIZON-GEA-01 trial enrolled 914 adults with previously untreated, unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma. Researchers assessed the results after a median 35.3 months of follow-up; the data cutoff was July 15, 2026.
In the group receiving zanidatamab-hrii (Ziihera), tislelizumab-jsgr (Tevimbra) and chemotherapy, median overall survival was 27.0 months. The corresponding figures were 22.9 months with zanidatamab and chemotherapy, and 19.6 months with trastuzumab and chemotherapy. Estimated survival at 36 months was 39.8%, 31.5% and 22.9%, respectively. Compared with the trastuzumab combination, the three-drug regimen had a hazard ratio for death of 0.65 (95% confidence interval [CI], 0.52-0.80).
Zanidatamab with chemotherapy also improved overall survival compared with trastuzumab and chemotherapy: 22.9 months versus 19.6 months, with a hazard ratio of 0.76 (95% CI, 0.62-0.93; P=0.0088). BeOne said this result fulfilled the trial’s other primary objective.
The direct comparison of the three-drug regimen with zanidatamab and chemotherapy yielded median overall survival of 27.0 months versus 22.9 months. The hazard ratio was 0.81 (95% CI, 0.65-1.00; P=0.0502). BeOne said the difference did not reach statistical significance in an underpowered analysis. Subgroup results also did not establish a significant benefit by PD-L1 TAP: the hazard ratio was 0.76 (95% CI, 0.52-1.10) for TAP below 1%, and 0.77 (95% CI, 0.58-1.02) for TAP of 1% or higher.
The U.S. Food and Drug Administration (FDA) approved both zanidatamab regimens on Aug. 25, 2026, as first-line treatments for adults with HER2-positive, unresectable locally advanced or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. The regimen with tislelizumab and chemotherapy is for IHC 3+ or IHC 2+/ISH-positive disease; zanidatamab with chemotherapy is for IHC 3+ disease.
