BeOne Medicines has 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 or without Tevimbra (tislelizumab), as a first-line treatment for patients with HER2-positive locally advanced or metastatic Gastroesophageal Adenocarcinoma (GEA).

At IA2, the Ziihera plus chemotherapy regimen demonstrated a statistically significant and clinically meaningful improvement in Overall Survival (OS) compared with trastuzumab plus chemotherapy, meeting the study’s remaining primary endpoint analysis.

The IA2 results also provided longer-term follow-up for patients receiving Tevimbra in combination with Ziihera and chemotherapy. The regimen continued to demonstrate durable outcomes, with an improved OS hazard ratio and a generally manageable safety profile. The findings reinforce the results from the first interim analysis (IA1), in which the combination met both Progression-Free Survival (PFS) and OS endpoints, with the OS benefit observed across different PD-L1 and HER2 expression levels.

The latest findings come shortly after the US Food and Drug Administration (FDA) approved supplemental Biologics License Applications (sBLAs) for Ziihera and Tevimbra on August 25, 2026. The approvals cover their use with chemotherapy as a first-line treatment for adults with unresectable, locally advanced or metastatic HER2-positive gastric, gastroesophageal junction or esophageal adenocarcinoma.

According to BeOne, the approved immunotherapy-based regimen is the first FDA-approved treatment in this setting to demonstrate a median overall survival exceeding two years regardless of PD-L1 status. The FDA decision was based on IA1 results, which were published earlier this year in The New England Journal of Medicine.

At IA2, the safety profiles of both Ziihera plus chemotherapy and Tevimbra plus Ziihera and chemotherapy remained generally consistent with earlier findings and the known safety profiles of the individual treatment components. No new safety signals were identified.

HERIZON-GEA-01 is a global, randomised, open-label Phase 3 trial conducted jointly with Jazz Pharmaceuticals. The study enrolled 914 patients across approximately 300 sites in more than 30 countries. Participants were randomised to receive Ziihera plus chemotherapy and Tevimbra, Ziihera plus chemotherapy, or trastuzumab plus chemotherapy. The trial assessed PFS by blinded independent central review and OS as its dual primary endpoints.

Ziihera is a HER2-directed bispecific antibody designed to bind two extracellular sites on the HER2 receptor. By targeting HER2 through multiple mechanisms, zanidatamab is designed to promote receptor internalization and immune-mediated tumour cell killing.

Tevimbra is a humanized IgG4 anti-PD-1 monoclonal antibody designed to target PD-1 and support the immune system’s ability to recognise and attack tumour cells. It forms a key component of BeOne’s solid tumour portfolio and is being evaluated across multiple cancer types and treatment settings.

The IA2 results have been submitted for presentation at a major medical meeting in the fourth quarter of 2026.