Key Takeaways:
Ziihera (zanidatamab-hrii) plus chemotherapy met the overall survival endpoint in first-line HER2+ gastroesophageal adenocarcinoma, Jazz said, with the hazard ratio improving versus the first interim.
"These HERIZON-GEA-01 results show that Ziihera-based regimens extend OS, demonstrating definitive superiority of Ziihera over trastuzumab and setting a new benchmark for what a first-line HER2-targeted therapy can achieve," Kohei Shitara, director of gastrointestinal oncology at Japan's National Cancer Center Hospital East and principal trial investigator, said.
The second interim analysis of the Phase 3 HERIZON-GEA-01 trial randomized 914 patients across more than 30 countries to Ziihera plus chemotherapy, Ziihera plus tislelizumab (Tevimbra) and chemotherapy, or trastuzumab plus chemotherapy. In the primary analysis presented at the 2026 ASCO Gastrointestinal Cancers Symposium, the three-drug regimen reached a median overall survival of 26.4 months versus 19.2 months for trastuzumab plus chemotherapy, a hazard ratio of 0.72 (a 28 percent lower risk of death). Median progression-free survival was 12.4 months versus 8.1 months, a hazard ratio of 0.63.
The FDA on Aug. 25 approved Ziihera plus tislelizumab and chemotherapy for first-line HER2+ (IHC 3+ and IHC 2+/ISH+) unresectable locally advanced or metastatic GEA, and Ziihera plus chemotherapy for IHC 3+ disease. Jazz has submitted the updated data for presentation at a major medical meeting in the fourth quarter and plans to file with global health authorities.
With longer follow-up, the Ziihera plus tislelizumab and chemotherapy arm also improved its overall survival hazard ratio versus the first interim, building on results published in the New England Journal of Medicine. The safety profile was consistent with the known profiles of each agent, with no new signals. Diarrhea occurred in 85 percent of patients on the three-drug regimen and 81 percent on Ziihera plus chemotherapy, with boxed warnings for diarrhea and embryo-fetal toxicity. Left ventricular dysfunction was reported in 9 percent and 5 percent of patients, respectively.
GEA, including cancers of the stomach, gastroesophageal junction and esophagus, is the fifth most common cancer worldwide, and about 20 percent of patients have HER2+ disease. The five-year survival rate for metastatic disease is below 10 percent. Ziihera, developed by Jazz and BeOne Medicines under license from Zymeworks, is also approved for previously treated HER2+ biliary tract cancer.
The data positions Ziihera to displace trastuzumab as the HER2-targeted backbone in first-line GEA, a market Jazz's chief medical officer Rob Iannone said the company is moving quickly to capture. Investors will watch the fourth-quarter medical meeting presentation for the full updated survival curves.
This article is for informational purposes only and does not constitute investment advice.
