Tevimbra/Ziihera combination granted priority review to treat gastric cancer

The FDA has granted priority review for a supplemental biologics license application (sBLA) for Tevimbra (tislelizumab) in combination with Ziihera (zanidatamab) and chemotherapy for the first-line treatment of unresectable locally advanced/metastatic HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma.

The submission is under review through the agency’s Real-Time Oncology Review (RTOR) program. The Prescription Drug User Fee Act (PDUFA) date has been set for Aug. 25, 2026.

Gastroesophageal adenocarcinoma, including cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide. Approximately 20% of patients have HER2+ disease, which has high morbidity and mortality. The global five-year survival rate is less than 30% for gastric cancer and about 19% for gastroesophageal adenocarcinoma.

Developed by BeOne Medicines, Tevimbra is humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody. It is already approved in combination with chemotherapy for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1.

In esophageal cancer, Tevimbra is approved as a single agent in adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after chemotherapy and in combination with chemotherapy for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1.

Ziihera, developed by Jazz Pharmaceuticals, is a bispecific HER2-directed antibody that has been granted accelerated approval to treat adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer.

The submission is based on data from HERIZON-GEA-01, a phase 3 clinical trial that is being conducted jointly by BeOne and Jazz Pharmaceuticals. The trial enrolled 914 patients who have unresectable, locally advanced, recurrent, or metastatic HER2+ adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction.

Patients were randomized to three trial arms: Ziihera in combination with chemotherapy and Tevimbra; Ziihera in combination with chemotherapy; and trastuzumab plus chemotherapy.

In the Tevimbra/Ziihera arm, the trial resulted in an overall survival of 26.4 months at the first interim analysis. The Ziihera plus chemotherapy arm achieved a median overall of 24.4 months, and the control arm resulted in a median overall survival of 19.2 months. Both arms with Ziihera delivered a statistically significant and clinically meaningful improvement in median progression-free survival of 12.4 months compared with 8.1 months in the control arm.

Adding Tevimbra to Ziihera resulted in a 28% reduction in the risk of death and a greater than seven-month improvement in median overall survival. Improvement in overall survival and progression-free survival was seen regardless of PD-L1 status.

The results from the HERIZON-GEA-01 trial were presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January 2026.

“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,” 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, said in a news release in January.

No new safety signals were identified. The most common grade 3 or greater treatment-related adverse event was diarrhea. Discontinuation of either Ziihera or trastuzumab due to treatment-related diarrhea was uncommon. Treatment-emergent diarrhea generally occurred early in treatment and resolved within three weeks.