By Fineline Cube 
BeOne Medicines Ltd. (NASDAQ: ONC, HKG: 6160, SHA: 688235) announced its HER2‑targeted bispecific antibody zanidatamab (Ziihera) met both primary PFS and OS endpoints in the HERIZON‑GEA‑01 Phase 3 trial for first‑line HER2‑positive locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), with the tislelizumab triple combo demonstrating a statistically significant survival benefit over trastuzumab plus chemotherapy.
Trial Milestone
| Item | Detail |
|---|---|
| Product | zanidatamab (Ziihera) |
| Mechanism | HER2‑targeted bispecific antibody |
| Indication | HER2‑positive locally advanced/metastatic GEA (gastric, GEJ, esophageal) |
| Trial | HERIZON‑GEA‑01 Phase 3 |
| Primary Endpoints | PFS and OS (both met) |
| Control Arm | trastuzumab + chemotherapy |
| Combination Arms | zanidatamab + chemotherapy; zanidatamab + tislelizumab + chemotherapy |
| Key Result | Triple combo shows statistically significant OS benefit; double combo shows OS trend |
| Next Step | Additional OS interim analysis for double combo mid‑2026 |
Drug Profile
- Class: First‑in‑class HER2‑targeted bispecific antibody; brand name Ziihera
- Combination Strategy: Evaluated with tislelizumab (Tevimbra), BeOne’s PD‑1 inhibitor, plus standard chemotherapy
- Differentiation: Dual HER2 epitope binding may overcome resistance vs. monoclonal antibodies like trastuzumab
- Pipeline: HERIZON‑GEA‑01 is the pivotal trial supporting global regulatory submissions
Clinical Evidence Summary
| Regimen | PFS Result | OS Result |
|---|---|---|
| zanidatamab + tislelizumab + chemo | Highly statistically significant improvement vs control | Clinically meaningful and statistically significant improvement vs control |
| zanidatamab + chemo | Highly statistically significant improvement vs control | Clinically meaningful benefit, clear trend toward statistical significance |
Note: Full hazard ratios and confidence intervals will be presented at an upcoming medical conference.
Market Impact & Outlook
- GEA Market: ~1.1 million new cases globally in 2025; HER2‑positive subset represents ~20‑25% of gastric/GEJ cancers
- Standard of Care: Trastuzumab plus chemo remains first‑line; no HER2‑targeted therapy has shown OS benefit in combination with PD‑1 inhibition in this setting
- Regulatory Path: BeOne plans NDA submissions to NMPA, FDA, and EMA in H2 2026 based on HERIZON‑GEA‑01 results
- Commercial Potential: Analysts project global peak sales potential of $2.5‑3.5 billion if approved across major markets
- Competitive Landscape: Positions ahead of Roche’s trastuzumab and Daiichi’s ENHERTU in first‑line HER2‑positive GEA
Forward‑Looking Statements
This brief contains forward‑looking statements regarding zanidatamab’s clinical development, regulatory submissions, and commercial outlook. Actual results may differ materially due to risks including final data readouts, regulatory review outcomes, and market competition.-Fineline Info & Tech