Ziihera Meets Overall Survival Endpoint at HERIZON-GEA-01 Second Interim, Completing the Phase 3 Win

BeOne Medicines and Jazz Pharmaceuticals said Monday that the second interim analysis of the Phase 3 HERIZON-GEA-01 trial met the overall survival co-primary endpoint for Ziihera (zanidatamab-hrii) plus chemotherapy in first-line HER2-positive gastroesophageal adenocarcinoma, completing the study’s dual primary endpoints six days after U.S. regulators cleared the regimen.

At the second interim analysis, Ziihera plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival versus trastuzumab plus chemotherapy. It is the first time the doublet has crossed the significance threshold on survival; at the first interim readout in November 2025, that arm showed only a strong trend toward significance.

Longer follow-up on the triplet arm, Tevimbra (tislelizumab) plus Ziihera and chemotherapy, showed an improved overall survival hazard ratio and durable outcomes. The safety profile was consistent with the first interim analysis and the known profiles of each agent, with no new safety signals.

The readout comes days after the FDA on Aug. 25 approved supplemental Biologics License Applications for both Ziihera and Tevimbra in combination with chemotherapy for first-line HER2+ gastric, gastroesophageal junction, or esophageal adenocarcinoma. That decision, based on the first interim analysis published in the New England Journal of Medicine, made the triplet the first immunotherapy-based regimen in the setting to show median overall survival exceeding two years regardless of PD-L1 status.

HERIZON-GEA-01 randomized 914 patients across roughly 300 sites in more than 30 countries, comparing Ziihera plus chemotherapy with and without Tevimbra against trastuzumab plus chemotherapy on dual primary endpoints of progression-free survival by blinded independent central review and overall survival.

The survival readout is especially meaningful for BeOne, which holds Ziihera rights across much of Asia, excluding India and Japan, where the burden of gastroesophageal cancer is high. Jazz holds rights in all other regions, and the two companies develop zanidatamab under license from Zymeworks.

BeOne shares closed Friday at $366.73; Jazz closed at $244.54. The second interim analysis results have been submitted for presentation at a major medical meeting in the fourth quarter.

For the approval, label, and trial details, see our coverage of the Aug. 25 first-line approval. The full press release is available from BeOne Medicines.