As reported on PharmaBiz, BeOne Medicines has reported positive results from the second interim analysis of the phase 3 HERIZON-GEA-01 trial, further supporting the use of zanidatamab (Ziihera)-containing regimens as first-line treatment for patients with HER2-positive advanced gastroesophageal adenocarcinoma (GEA).
The latest analysis demonstrated that zanidatamab plus chemotherapy achieved a statistically significant improvement in overall survival compared with trastuzumab combined with chemotherapy, fulfilling the study’s remaining primary endpoint. The findings add to previously reported efficacy data and provide additional evidence for the potential role of the HER2-targeted therapy in the frontline setting.
Updated results were also reported for the investigational regimen combining the anti-PD-1 antibody tislelizumab (Tevimbra), zanidatamab, and chemotherapy. With longer follow-up, the triplet combination continued to show durable clinical benefit and an improved overall survival hazard ratio, while maintaining a safety profile considered manageable and consistent with earlier observations.
According to BeOne Medicines, the new data build upon outcomes from the first interim analysis, which showed significant improvements in both progression-free survival and overall survival. In that earlier evaluation, survival advantages were observed across patient subgroups regardless of PD-L1 expression or HER2 levels.
Commenting on the findings, Mark Lanasa, MD, PhD, Chief Medical Officer for Solid Tumors at BeOne Medicines, stated that the results provide additional phase 3 evidence supporting meaningful survival improvements across both experimental treatment arms evaluated in HERIZON-GEA-01. He also highlighted the significance of expanding access to zanidatamab, particularly in Asia, where gastroesophageal cancers remain a major health burden and where BeOne retains commercialization rights in several markets.
The announcement follows recent regulatory progress in the United States. On August 25, 2026, the US Food and Drug Administration approved supplemental biologics license applications for zanidatamab and tislelizumab, each administered with chemotherapy, for the treatment of adults with unresectable locally advanced or metastatic HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma.
The FDA decision was based on data from the first interim analysis of HERIZON-GEA-01, results that were published earlier in 2026 in The New England Journal of Medicine. The approved immunotherapy-containing regimen became the first treatment approach in this disease setting to demonstrate median overall survival exceeding two years irrespective of PD-L1 status.
Safety findings from the second interim analysis were generally in line with the established safety profiles of the individual agents and remained consistent with data reported previously. Investigators did not identify any new safety signals.
BeOne indicated that the second interim analysis results have been submitted for presentation at a major scientific congress scheduled for the fourth quarter of 2026.
About HERIZON-GEA-01
HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label phase 3 study conducted in collaboration with Jazz Pharmaceuticals. The trial enrolled 914 patients at approximately 300 sites across more than 30 countries.
Eligible participants had unresectable locally advanced, recurrent, or metastatic HER2-positive gastroesophageal adenocarcinoma involving the stomach, esophagus, or gastroesophageal junction. HER2 positivity was defined centrally as immunohistochemistry (IHC) 3+ or IHC 2+ with positive in situ hybridization testing.
Patients were randomly assigned to one of three treatment groups:
- Zanidatamab plus chemotherapy and tislelizumab
- Zanidatamab plus chemotherapy
- Trastuzumab plus chemotherapy
The trial’s dual primary endpoints are progression-free survival, assessed by blinded independent central review, and overall survival.
Zanidatamab and Tislelizumab
Zanidatamab is a bispecific HER2-directed antibody engineered to bind two distinct extracellular HER2 epitopes. The agent is designed to reduce HER2 receptor expression on tumor cells and activate multiple antitumor mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis.
The therapy is under investigation across several HER2-expressing solid tumors. In addition to its newly approved indication in gastroesophageal cancer, zanidatamab has received approval in China for previously treated HER2-high biliary tract cancer and holds accelerated approval in the United States as well as conditional marketing authorization in the European Union for eligible biliary tract cancer patients.
Development of zanidatamab is being carried out by Jazz Pharmaceuticals and BeOne Medicines under licensing agreements with Zymeworks, the company that originally discovered the molecule. BeOne holds rights in Asia excluding India and Japan, as well as in Australia and New Zealand, while Jazz controls commercialization rights in other territories.
Tislelizumab is an anti-PD-1 monoclonal antibody designed to minimize interaction with Fc-gamma receptors on macrophages, an approach intended to enhance immune-mediated antitumor activity. The agent represents a key component of BeOne’s solid tumor portfolio and has been studied extensively, with nearly 15,000 patients enrolled across more than 70 clinical trials in over 30 countries and regions. To date, more than 2 million patients worldwide have received the therapy across approved indications.
BeOne Medicines continues to advance a broad oncology pipeline spanning both hematologic malignancies and solid tumors through internal research programs and external partnerships aimed at accelerating the development of new cancer therapies.
