Ziihera Plus Chemotherapy Demonstrates Significant Overall Survival Benefit in Phase 3 HERIZON-GEA-01 Trial in First-Line HER2-Positive Gastroesophageal Adenocarcinoma – BeOne Medicines
31 August 2026 – BeOne Medicines Ltd. announced positive topline results from the second interim analysis (IA2) of the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera (zanidatamab), in combination with chemotherapy, with and without Tevimbra (tislelizumab), as first-line treatment for HER2+ locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). At IA2, Ziihera plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with trastuzumab plus chemotherapy, meeting the remaining primary endpoint analysis of the study.
IA2 also provided longer follow-up data for the Tevimbra plus Ziihera and chemotherapy regimen, demonstrating an improved OS hazard ratio, continued durable outcomes, and a generally manageable safety profile. These results reinforce findings from IA1, in which the regimen met the progression-free survival (PFS) and OS endpoints, with the overall survival benefit observed across PD-L1 and HER2+ expression levels.
“Today’s results, coming just days after FDA approval of the HERIZON-GEA-01 regimens, add to a series of important milestones demonstrating their potential to transform the treatment of HER2-positive GEA. We now have compelling Phase 3 evidence of statistically significant and clinically meaningful overall survival results across both HERIZON-GEA experimental arms, reinforcing the opportunity to improve outcomes for patients beginning first-line treatment. This latest result is also particularly meaningful for BeOne given our rights to Ziihera across much of Asia, where the burden of gastroesophageal cancer is substantial, as we work to bring these treatment options to more patients around the world.” – Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne Medicines.
Recent FDA approval establishes HERIZON-GEA-01 regimen as potential new standard of care
On August 25 2026, the U.S. Food and Drug Administration (FDA) approved supplemental Biologics License Applications (sBLAs) for both Ziihera and Tevimbra in combination with chemotherapy for the first-line treatment of adult patients with unresectable locally advanced or metastatic HER2+ gastric, gastroesophageal junction, or esophageal adenocarcinoma, making it the first FDA-approved immunotherapy-based regimen in this setting to demonstrate median OS exceeding two years, regardless of PD-L1 status. The approval was based on results from IA1 of HERIZON-GEA-01, which were published in The New England Journal of Medicine earlier this year.
The safety profile of Ziihera plus chemotherapy and Tevimbra plus Ziihera and chemotherapy at IA2 was generally consistent with that of IA1 and the known safety profiles of the individual treatment components, with no new safety signals identified.
The results from IA2 have been submitted for presentation at a major medical meeting in the fourth quarter of 2026.
About the HERIZON-GEA-01 Phase 3 Trial
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with Jazz Pharmaceuticals, to evaluate and compare the efficacy and safety of Ziihera plus chemotherapy, with and without Tevimbra, to the standard of care (trastuzumab plus chemotherapy) as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: Ziihera in combination with chemotherapy and Tevimbra; Ziihera in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial evaluated dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
