BeOne Medicines Ltd. announced positive top-line results from the Phase 3 HERIZON-GEA-01 trial evaluating ZIIHERA (zanidatamab), a HER2-targeted bispecific antibody, in combination with chemotherapy, with or without PD-1 inhibitor TEVIMBRA (tislelizumab), as first-line treatment for HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction, and esophagus. Both ZIIHERA plus TEVIMBRA and chemotherapy and ZIIHERA plus chemotherapy demonstrated clinically meaningful and highly statistically significant improvements in progression-free survival (PFS) compared to the control arm, trastuzumab plus chemotherapy. ZIIHERA plus TEVIMBRA and chemotherapy also demonstrated clinically meaningful and statistically significant improvements in overall survival (OS), and ZIIHERA plus chemotherapy demonstrated a clinically meaningful effect with a strong trend toward statistical significance for OS compared to the control arm at the time of this first analysis.
The trial is ongoing with an additional planned OS interim analysis for ZIIHERA plus chemotherapy currently expected in mid-2026. These PFS and OS benefits were observed in the ZIIHERA plus TEVIMBRA and chemotherapy arm versus the control arm in both PD-L1 positive and PD-L1 negative subgroups. Supportive of the primary efficacy endpoints, both combination arms demonstrated improvements in the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) versus the control arm.
The safety profile of ZIIHERA in combination with chemotherapy, with and without TEVIMBRA, was generally consistent with the known safety profile of each agent with no new safety signals observed in the two investigational combination arms and supports the overall benefit-risk profile of ZIIHERA for use in this indication. These data will be submitted for presentation at a major medical meeting in the first quarter of 2026. 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 ZIIHERAplus chemotherapy, with or 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. Appropriate 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: ZIIHERAin combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy.
The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
