BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced full results from the Phase 3 HERIZON-GEA-01 trial evaluating ZIIHERA (zanidatamab), a HER2-targeted bispecific antibody, in combination with chemotherapy, with and without PD-1 inhibitor TEVIMBRA (tislelizumab), as a first-line treatment for HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). These data, including the first interim overall survival (OS) analysis, will be presented as a Late-Breaking Abstract Oral Presentation (#LBA285) at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) on January 8, 2026, from 8:57- 9:07 a.m. PST.
HERIZON-GEA-01 met the dual primary endpoint of progression-free survival (PFS), 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 (OS) (mOS: 26.4 months, HR=0.72 [95% CI: 0.57, 0.90]; P=0.0043), 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 < 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.
“The HERIZON-GEA-01 results are encouraging, with median overall survival for tislelizumab plus zanidatamab and chemotherapy surpassing two years, an outcome that marks a significant advancement in the treatment of metastatic HER2+ gastroesophageal adenocarcinoma,” said Manish Shah, M.D., Chief of the Solid Tumor Service and Director of Gastrointestinal Oncology at Weill Cornell Medicine and a medical oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, who serves as a paid advisory board member for Jazz Pharmaceuticals, Inc. and BeOne Medicines Ltd. “Unlike prior studies in HER2+ GEA with checkpoint blockade therapy, the addition of tislelizumab demonstrated meaningful activity even in TAP PD-L1 < 1%, suggesting a potential new treatment option for this subgroup, while broadening choices for patients with PD-L1 ≥1%.”
Further highlights from the HERIZON-GEA-01 results include:
- TEVIMBRA added to ZIIHERA and chemotherapy (n=302; mPFS: 12.4 months, HR=0.63 [95% CI: 0.51, 0.78], P=<0.0001) 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 (n=304; mPFS: 12.4 months, HR=0.65 [95% CI: 0.52, 0.81], P=<0.0001) 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 (TAP score <1%), the HR results for PFS were 0.47 [95% CI: 0.32, 0.69] in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.49 [95% CI: 0.33, 0.73].
- In the PD-L1 positive subgroup (TAP score >1%), the HR results for PFS were 0.65 [95% CI: 0.49, 0.86] in the ZIIHERA plus TEVIMBRA and chemotherapy arm and the HR results for OS were 0.82 [95% CI: 0.60, 1.10].
- Both experimental arms demonstrated improvements in the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) versus the control arm, with ZIIHERA and chemotherapy resulting in an ORR of 69.6% with a median DOR of 14.32 months (CI 95%: 11.53, 21.85). The ZIIHERA plus TEVIMBRA and chemotherapy arm induced an ORR of 70.7%, with the median DOR reaching 20.70 months (CI 95%: 12.55, 37.65), highlighting TEVIMBRA’s essential role in the durability of response observed with the regimen.
“The comprehensive results of the HERIZON-GEA-01 study, particularly the improvement in overall survival shown in the TEVIMBRA plus ZIIHERA and chemotherapy arm, pave the way for the adoption of a new standard in first-line HER2-positive metastatic GEA,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne. “BeOne holds commercial rights for ZIIHERA in most of Asia Pacific, where the GEA burden is highest. With these data, we anticipate the opportunity to expand access so more patients can benefit.”
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 ≥3 treatment-related adverse events (TRAEs) 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 ≥3 treatment-related adverse event (TRAE) was diarrhea (24.5% of patients with ZIIHERA plus TEVIMBRA and chemotherapy; 20.0% with ZIIHERA plus chemotherapy; and 12.9% of patients in the trastuzumab plus chemotherapy arm). Importantly, discontinuation of either ZIIHERA or trastuzumab due to treatment-related diarrhea was uncommon (4.1% of patients with ZIIHERA plus TEVIMBRA and chemotherapy, 1.3% with ZIIHERA plus chemotherapy, and 0% of patients in the trastuzumab plus chemotherapy arm). 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.
These results will be submitted for publication in a peer-reviewed journal. BeOne intends to submit supplemental Biologics License Applications to the U.S. FDA for TEVIMBRA and to the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for TEVIMBRA and ZIIHERA, based on these data. The company also intends to work with authorities in its licensed territories to expedite regulatory submissions in these markets.
* Article first published on: itweb.africa
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