Ziihera plus Tevimbra® (tislelizumab-jsgr) and fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+), and Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+).
"This approval is a major step forward for people with HER2+ advanced GEA. Ziihera is now the first and only bispecific HER2-targeted antibody combined with a PD-1 inhibitor and chemotherapy approved for all HER2+ advanced GEA patients, regardless of PD-L1 status, establishing a new standard of care in first-line treatment," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals.
"The HERIZON-GEA-01 results include the longest median overall survival reported in a Phase 3 trial in this setting, at 26.4 months. We are grateful to the gastric cancer community, including patients, caregivers, investigators and advocacy organizations, whose partnership made this possible."
GEA, which includes gastric, gastroesophageal junction and esophageal cancers, is the fifth most common cancer worldwide and remains associated with poor outcomes despite advances in treatment.1 Approximately 20% of patients have HER2+ disease.2,3,4 In the United States, more than 31,000 new stomach cancer cases are diagnosed each year.5
"People with advanced HER2+ GEA deserve treatment options that reflect the unique biology of their disease. Understanding what a HER2+ diagnosis means is an important part of navigating treatment decisions and helping patients and families make informed choices about care. Today's approval gives people diagnosed with HER2+ GEA a much-needed new treatment option and more choice in how their cancer is treated," said Martha Raymond, MA, CEO and founder of GI Cancers Alliance.
The approval is based on results from the Phase 3 HERIZON-GEA-01 trial, which were published in the New England Journal of Medicine and first presented at ASCO GI 2026, with PD-L1 subgroup data presented at ASCO 2026. The trial remains ongoing, with additional analyses planned.
Key HERIZON-GEA-01 Results
- Progression-free survival (PFS): Both Ziihera-containing combinations significantly improved PFS in the overall HER2+ population, reducing the risk of disease progression or death by 35% and extending median PFS to 12.4 months versus 8.1 months with trastuzumab plus chemotherapy.
- Overall survival (OS): In the overall HER2+ population, Ziihera plus tislelizumab-jsgr and chemotherapy demonstrated a statistically significant and clinically meaningful OS benefit, reducing the risk of death by 28% compared with trastuzumab plus chemotherapy and achieving a median OS of 26.4 months versus 19.2 months, representing a greater than seven-month improvement and the longest median OS reported in a Phase 3 trial in HER2+ advanced GEA.
- PFS and OS benefits were generally consistent across major prespecified subgroups, including geographic region and PD-L1 status.
- Ziihera-containing regimens demonstrated a manageable safety profile consistent with prior zanidatamab studies, with diarrhea as the most common adverse reaction, predominantly early in onset. Loperamide prophylaxis was administered during the first cycle, and diarrhea was managed with antidiarrheals and treatment modifications as needed, resulting in few discontinuations of Ziihera.
"This approval represents an important advancement in the treatment of metastatic HER2+ GEA," said Geoffrey Ku, M.D., HERIZON-GEA-01 study co-author and associate attending physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. "Importantly, similar outcomes were seen in patients whose tumors were PD-L1 positive or PD-L1 negative, suggesting that this regimen has the potential to benefit a broad range of patients. It further underscores what we have known for more than 15 years: HER2 testing at the time of diagnosis for advanced or metastatic gastroesophageal adenocarcinoma is critical to optimally guide treatment selection."
The company will host an investor webcast on Tuesday, August 25, at 4:30 p.m. ET / 9:30 p.m. IST to discuss the FDA approval of Ziihera in first-line HER2+ GEA and provide updates on the zanidatamab development program. The webcast may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website.
About Gastroesophageal Adenocarcinoma
GEA, including cancers of the stomach, gastroesophageal junction, and esophagus, is the fifth most common cancer worldwide, and approximately 20% of patients have HER2+ disease.1,2,3,4 HER2+ GEA has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 10% for metastatic disease.6
About Ziihera® (zanidatamab-hrii)
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces CDC, ADCC, and ADCP. These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.7
Gastroesophageal adenocarcinoma (GEA): In the United States, Ziihera is indicated for the first-line treatment of adults with HER2+ locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus, in combination with tislelizumab-jsgr and fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ and IHC 2+/ISH+ as detected by an FDA-authorized test); and in combination with fluoropyrimidine- and platinum-containing chemotherapy (HER2+ IHC 3+ as detected by an FDA-authorized test).
Biliary tract cancer (BTC): In the United States, Ziihera is also indicated for the treatment of adults with previously treated, unresectable or metastatic HER2+ (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.7 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).7 Ziihera is also approved in the European Union and other countries.
Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeOne Medicines under license agreements from Zymeworks, which first developed the molecule.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with rare disease — often with limited or no therapeutic options. We have a diverse portfolio of medicines, including leading therapies addressing epilepsies, cancers and sleep disorders. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide.
For more information please visit www.jazzpharmaceuticals.com
