BeOne Medicines Announces Phase 3 Results for ZIIHERA

BeOne Medicines (ONC) announced full results from the Phase 3 HERIZON-GEA-01 trial evaluating ZIIHERA, a HER2-targeted bispecific antibody, in combination with chemotherapy, with and without PD-1 inhibitor TEVIMBRA, as a first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma. These data, including the first interim overall survival analysis, will be presented as a Late-Breaking Abstract Oral Presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium on January 8, 2026, from 8:57- 9:07 a.m. PST. HERIZON-GEA-01 met the dual primary endpoint of progression-free survival, demonstrating statistically significant and clinically meaningful improvements in both experimental arms compared to the control arm. The addition of TEVIMBRA to ZIIHERA and chemotherapy also showed a statistically significant and clinically meaningful improvement in overall survival, resulting in a 28% reduction in the risk of death and a greater than 7-month improvement in mOS. These PFS and OS benefits were observed in the ZIIHERA plus TEVIMBRA and chemotherapy arm versus the control arm regardless of PD-L1 expression level, with approximately one-third of enrolled patients with tumors classified as PD-L1 less than 1%. ZIIHERA plus chemotherapy showed a clinically meaningful survival benefit with a mOS of 24.4 months, a strong trend toward statistical significance at the time of this first interim analysis for OS. Further highlights from the HERIZON-GEA-01 results include: TEVIMBRA added to ZIIHERA and chemotherapy resulted in a 37% reduction in the risk of disease progression and a greater than 4-month improvement in mPFS. Patients receiving ZIIHERA plus chemotherapy showed a 35% reduction in the risk of disease progression and a similar greater than 4-month improvement in mPFS. These results compare favorably to mPFS of 8.1 months in patients treated with trastuzumab plus chemotherapy. In the PD-L1 negative subgroup, the HR results for PFS were 0.47 in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.49. In the PD-L1 positive subgroup, the HR results for PFS were 0.65 in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.82. Both experimental arms demonstrated improvements in the key secondary endpoints of objective response rate and duration of response versus the control arm, with ZIIHERA and chemotherapy resulting in an ORR of 69.6% with a median DOR of 14.32 months. The ZIIHERA plus TEVIMBRA and chemotherapy arm induced an ORR of 70.7%, with the median DOR reaching 20.70 months, highlighting TEVIMBRA's essential role in the durability of response observed with the regimen. The safety profile of ZIIHERA in combination with chemotherapy, with or without TEVIMBRA, was consistent with the known effects of HER2-directed therapy and immunotherapy, and no new safety signals were identified. Duration of treatment was longest on the ZIIHERA plus TEVIMBRA and chemotherapy arm. Rates of Grade greater than or equal to3 treatment-related adverse events were 71.8% with ZIIHERA plus TEVIMBRA and chemotherapy, 59.0% with ZIIHERA plus chemotherapy, and 59.6% with trastuzumab plus chemotherapy. Rates of discontinuation of ZIIHERA or trastuzumab due to TRAEs were 11.9% with ZIIHERA plus TEVIMBRA and chemotherapy, 8.5% with ZIIHERA plus chemotherapy, and 2.3% in the trastuzumab plus chemotherapy arm. The most common Grade greater than or equal to3 treatment-related adverse event was diarrhea. Importantly, discontinuation of either ZIIHERA or trastuzumab due to treatment-related diarrhea was uncommon/ Treatment-emergent diarrhea generally occurred early in treatment and resolved within 3 weeks. The manageable safety profile supports the feasibility of these combinations in the first-line metastatic setting. Zanidatamab is being developed by Jazz (JAZZ) and BeOne under license agreements from Zymeworks (ZYME), which first developed the molecule.