Jazz Pharmaceuticals recently announced that the US Food and Drug Administration (FDA) approved 2 Ziihera (zanidatamab-hrii)-containing regimens for the first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive (HER2+) gastroesophageal adenocarcinoma (GEA): 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+).

Rob Iannone, MD, MSCE, Executive Vice President (EVP), Global Head of Research and Development (R&D), and Chief Medical Officer (CMO), Jazz Pharmaceuticals, said, "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. The HERIZON-GEA-01 results include the longest median Overall Survival (OS) 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 organisations, 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. Approximately, 20 percent of patients have HER2+ disease. In the US, more than 31,000 new stomach cancer cases are diagnosed each year.

Martha Raymond, MA, CEO and Founder, GI Cancers Alliance, said, "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."

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.

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 percent 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 percent compared with trastuzumab plus chemotherapy and achieving a median OS of 26.4 months versus 19.2 months, representing a greater than 7-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.

Geoffrey Ku, MD, HERIZON-GEA-01 study co-author and associate attending physician on the Gastrointestinal Oncology Service—Department of Medicine, Memorial Sloan Kettering Cancer Center, said, "This approval represents an important advancement in the treatment of metastatic HER2+ GEA. 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."