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Jazz Pharmaceuticals plc, a global biopharma company whose purpose is to innovate to transform the lives of patients and their families, announced two abstracts featuring key data for Ziihera (zanidatamab-hrii) have been accepted for presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) from January 8-10, 2026, in San Francisco. The phase 3 HERIZON-GEA-01 trial results in first-line HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA) were accepted as a late-breaking presentation. Additionally, a new post-hoc overall survival (OS) analysis from the HERIZON-BTC-01 phase 2b trial in previously treated HER2+ biliary tract cancer (BTC) will be presented, providing further information for this approved indication.
"We look forward to sharing the clinically meaningful results from the phase 3 HERIZON-GEA-01 trial with the oncology community at ASCO GI," 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. "Advanced HER2+ GEA, which includes cancers of the stomach, gastroesophageal junction and esophagus, remains an aggressive cancer with a poor prognosis and continues to be an area with limited progress for patients. This trial was designed to evaluate whether Ziihera plus chemotherapy, with or without tislelizumab, could improve on the current standard of care in first-line therapy. We believe these positive results support Ziihera as the HER2-targeted agent-of-choice and the Ziihera combinations to become the new standard of care for patients with HER2+ first-line metastatic GEA regardless of PD-L1 status. Alongside new analyses from the HERIZON-BTC-01 phase 2b trial, these presentations highlight the continued impact of our broad zanidatamab clinical programme and our commitment to advancing innovation across HER2-targeted cancers."
The phase 3 HERIZON-GEA-01 trial, conducted jointly with BeOne Medicines, is evaluating Ziihera in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra (tislelizumab), as first-line treatment for HER2+ locally advanced or metastatic GEA. As previously announced, both Ziihera plus chemotherapy and Ziihera plus tislelizumab and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival (PFS) compared to the control arm, trastuzumab plus chemotherapy. Ziihera plus tislelizumab and chemotherapy also demonstrated clinically meaningful and statistically significant improvements in overall survival (OS), and Ziihera plus chemotherapy demonstrated a clinically meaningful effect with a strong trend toward statistical significance for OS compared to the control arm at the time of this first analysis.
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. 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 30% for gastric cancer and about 19% for GEA.
Biliary tract cancer (BTC), which includes gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, are rare and aggressive epithelial tumors often associated with poor prognosis. Although they account for less than 1% of all human cancers, cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma and comprises approximately 10–15% of all primary liver cancers. Global mortality from BTC has risen in recent decades.
Because early symptoms are often vague or nonspecific, most BTCs are diagnosed at an advanced stage,8 when curative surgery is not an option. While chemotherapy and, more recently, immunotherapy-based combinations are used in the first-line setting, disease progression is common. In the absence of molecular profiling, treatment options following first-line therapy are largely limited to chemotherapy.
HER2 overexpression or amplification defines a distinct molecular subtype of BTC12 and is observed in approximately 26% of patients globally. HER2-positive BTC is associated with worse prognosis than HER2-negative disease. Across the U.S., Europe, and Japan, an estimated 12,000 people are diagnosed with HER2-positive BTC each year.
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumour cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumour growth inhibition and cell death in vitro and in vivo. In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-approved test. The US FDA granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
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 Pharmaceuticals and BeOne Medicines under license agreements from Zymeworks Inc., which first developed the molecule.
The FDA granted Breakthrough Therapy designation for zanidatamab's development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for first-line GEA. Additionally, zanidatamab has received Orphan Drug designations from the FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer.
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