Ziihera® (zanidatamab-hrii) Combinations Achieve Unprecedented Results in First-Line HER2+ Locally Advanced or Metastatic GEA Including More Than Two Years Median Overall Survival Benefit
Ziihera® (zanidatamab-hrii) Combinations Achieve Unprecedented Results in First-Line HER2+ Locally Advanced or Metastatic GEA Including More Than Two Years Median Overall Survival Benefit |
| [06-January-2026] |
Positive Phase 3 HERIZON-GEA-01 results support Ziihera as the HER2-targeted agent-of-choice in HER2+ first-line metastatic GEA and Ziihera plus chemotherapy to replace trastuzumab as the new standard of care, with or without tislelizumab regardless of PD-L1 status Late-breaking results to be presented at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI) on January 8, 2026 For U.S. media and investors only DUBLIN, Jan. 6, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive efficacy and safety results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera® (zanidatamab-hrii) in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra® (tislelizumab), as first-line treatment for adults with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus. The data will be presented as a late-breaking oral presentation at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco on January 8, 2026 from 8:57- 9:07 a.m. PST (abstract number: LBA285). The study found:
"Reaching more than two years of median overall survival in a global Phase 3 trial for HER2+ metastatic GEA is truly unprecedented," said Elena Elimova, M.D., Princess Margaret Cancer Centre, the presenting author of the late-breaking data. "The HERIZON-GEA-01 results represent the longest survival outcomes in a Phase 3 trial ever reported in this setting, with the zanidatamab plus tislelizumab and chemotherapy regimen improving median overall survival by more than seven months versus the control arm. The fact that both zanidatamab plus chemotherapy and zanidatamab plus tislelizumab and chemotherapy achieved median progression-free survival beyond one year further reinforces the depth and durability of benefit. These findings signal a meaningful step forward for patients who have historically faced very limited long-term outcomes." "The results of the HERIZON-GEA-01 study are practice-changing," said Geoffrey Ku, M.D., associate attending physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center and study co-author. "In addition to the progression-free survival and overall survival benefits, the remarkably long duration of response and consistent benefit across relevant subgroups, including PD-L1 positive and negative tumors, strongly suggest that zanidatamab plus chemotherapy, with or without tislelizumab, should become the new standard of care for patients with HER2+ first-line locally advanced unresectable or metastatic GEA." Efficacy Summary from HERIZON-GEA-01
* Did not reach statistical significance at the first interim OS analysis The safety profile of Ziihera in combination with chemotherapy, with or without tislelizumab, was consistent with the known effects of HER2-directed therapy and immunotherapy, and no new safety signals were identified. Duration of treatment was longest on the Ziihera plus tislelizumab and chemotherapy arm. Rates of Grade ≥3 treatment-related adverse events (TRAEs) were 71.8% with Ziihera plus tislelizumab and chemotherapy, 59.0% with Ziihera plus chemotherapy, and 59.6% with trastuzumab plus chemotherapy. Discontinuations due to Ziihera- or trastuzumab-related and treatment discontinuations due to adverse events were 11.9% with Ziihera plus tislelizumab and chemotherapy, 8.5% with Ziihera plus chemotherapy, and 2.3% in the trastuzumab plus chemotherapy arm. The most common Grade ≥3 TRAE was diarrhea (24.5% of patients with Ziihera plus tislelizumab and chemotherapy; 20.0% with Ziihera plus chemotherapy; and 12.9% of patients in the trastuzumab plus chemotherapy arm). Importantly, discontinuation of either Ziihera or trastuzumab due to treatment-related diarrhea was uncommon (4.1% of patients with Ziihera plus tislelizumab and chemotherapy, 1.3% with Ziihera plus chemotherapy, and 0% of patients in the trastuzumab plus chemotherapy arm). Treatment-emergent diarrhea generally occurred early in treatment and resolved within three weeks. The manageable safety profile supports the feasibility of these combinations in the first-line metastatic setting. "The strength of the HERIZON-GEA-01 data firmly positions Ziihera as the HER2-targeted agent-of-choice capable of reshaping first-line treatment for HER2+ metastatic GEA patients," 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. "These results signal a clear evolution beyond the current standards and give us strong conviction as we move rapidly toward FDA submission. We are equally energized by the momentum we see across our broader development program, and we continue to evaluate Ziihera in multiple HER2-driven tumor types, including in HER2+ metastatic breast cancer with the ongoing Phase 3 EmpowHER-303 trial. This is the kind of scientific advancement that can redefine outcomes for patients, and we are committed to delivering it with urgency." Jazz Pharmaceuticals will host an investor webcast on Friday, January 9, at 6:30 a.m. PT/9:30 a.m. ET to review the Ziihera data presented at the meeting. The webcast will include commentary from the company's senior management and Dr. Geoffrey Ku. 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 the Phase 3 HERIZON-GEA-01 Trial About Gastroesophageal Adenocarcinoma About Ziihera® (zanidatamab-hrii) 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 under license agreements from Zymeworks, 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. Important Safety Information for ZIIHERA
WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA. Left Ventricular Dysfunction ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients. Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions. The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%. Infusion-Related Reactions ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day. Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use. If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs. Diarrhea ZIIHERA can cause severe diarrhea. Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity. ADVERSE REACTIONS Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA. The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%). USE IN SPECIFIC POPULATIONS Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients. Geriatric Use Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older. No overall differences in safety or efficacy were observed between these patients and younger adult patients. The full U.S. Prescribing Information for ZIIHERA, including BOXED Warning, is available at: https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf ® TEVIMBRA (tislelizumab) is a registered trademark of BeOne Medicines. Dr. Ku has financial interests related to Jazz Pharmaceuticals. About Jazz Pharmaceuticals Cautionary Note Concerning Forward-Looking Statements Contacts: Media Contact: Jazz Investor Contact: ___________________________
SOURCE Jazz Pharmaceuticals plc | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Company Codes: NASDAQ-NMS:JAZZ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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