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Nearly 40% of patients alive at three years with Ziihera plus tislelizumab and chemotherapy, irrespective of PD-L1 status, achieving a median OS of 27 months
Mature HERIZON-GEA-01 results show Ziihera plus chemotherapy delivered statistically significant and clinically meaningful OS benefit, reducing the risk of death by 24% versus trastuzumab plus chemotherapy
For U.S . media and investors only
DUBLIN , Oct. 23, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced updated overall survival (OS) results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera ® (zanidatamab-hrii) in combination with chemotherapy, with or without Tevimbra ® (tislelizumab-jsgr), as first-line treatment for adults with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA). The results from the second interim, and final formal, analysis were presented as a late-breaking rapid oral presentation (LBA79) at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain .
"For patients with HER2+ advanced GEA, long-term survival remains difficult to achieve. With longer follow-up, Ziihera -containing regimens demonstrated a durable overall survival benefit, with nearly 40% of patients treated with Ziihera plus tislelizumab and chemotherapy alive at three years," said Dr. Kohei Shitara , director of the Department of Gastrointestinal Oncology , and principal trial investigator at the National Cancer Center Hospital East , Kashiwa, Japan . " Ziihera plus chemotherapy has also now demonstrated a statistically significant survival benefit over trastuzumab plus chemotherapy. Together, these findings provide strong evidence for Ziihera -containing regimens as the new HER2-directed first-line standard of care."
At the data cutoff, median follow-up was 35.3 months, 9.4 months longer than at the first interim analysis. Key findings included:
• Ziihera plus tislelizumab and chemotherapy sustained its OS benefit versus trastuzumab plus chemotherapy, with an improved HR: Median OS reached 27.0 months (95% confidence interval [CI]: 23.7-32.2), the longest reported in a Phase 3 trial in this setting, compared with 19.6 months with trastuzumab plus chemotherapy. The Ziihera plus tislelizumab and chemotherapy regimen reduced the risk of death by 35% (hazard ratio [HR] 0.65; 95% CI: 0.52-0.80), improving from an HR of 0.72 at the first interim analysis.
• Nearly 40% of patients receiving Ziihera plus tislelizumab and chemotherapy were alive at three years: Estimated 36-month OS was 39.8% with Ziihera plus tislelizumab and chemotherapy, 31.5% with Ziihera plus chemotherapy and 22.9% with trastuzumab plus chemotherapy.
• Ziihera plus chemotherapy demonstrated a statistically significant and clinically meaningful OS improvement versus trastuzumab plus chemotherapy: Median OS was 22.9 months (95% CI: 19.9-27.6) with Ziihera plus chemotherapy compared with 19.6 months (95% CI: 16.9-22.2) with trastuzumab plus chemotherapy. Ziihera plus chemotherapy reduced the risk of death by 24% (HR 0.76; 95% CI: 0.62-0.93; P=0.0088).
• Ziihera plus tislelizumab and chemotherapy showed a meaningful trend toward improved OS versus Ziihera plus chemotherapy: Median OS was approximately four months longer with Ziihera plus tislelizumab and chemotherapy than with Ziihera plus chemotherapy (27.0 versus 22.9 months; HR 0.81; 95% CI: 0.65-1.00; P=0.0502). The difference did not reach statistical significance. Mean duration of treatment was longest for Ziihera plus tislelizumab and chemotherapy (64.1 weeks): 11.5 weeks longer than Ziihera plus chemotherapy (52.6 weeks), and 21.8 weeks longer than trastuzumab plus chemotherapy (42.3 weeks).
• Safety profiles remained unchanged with longer follow-up: The safety profiles of both Ziihera -containing regimens were consistent with the first interim analysis, supporting the tolerability of prolonged treatment.
"These HERIZON-GEA-01 three-year landmark results demonstrate meaningful survival outcomes for patients with HER2+ advanced GEA," said Rob Iannone , M.D., M.S.C.E., executive vice president, global head of R&D, and chief medical officer of Jazz Pharmaceuticals . "The statistically significant survival benefit observed with Ziihera plus chemotherapy and the durable outcomes seen with Ziihera plus tislelizumab and chemotherapy cement Ziihera as the new HER2-targeted backbone therapy in first-line HER2+ advanced GEA."
The Ziihera -containing regimens were recently included as preferred therapies in the National Comprehensive Cancer Network ® (NCCN ® ) Clinical Practice Guidelines in Oncology ® for Gastric Cancer, and Esophageal and Esophagogastric Junction Cancers, and Ziihera plus tislelizumab and chemotherapy is the only preferred HER2+ regimen irrespective of PD-L1 status.
These results follow the August 25, 2026 , U.S. Food and Drug Administration (FDA) approval of two Ziihera -containing regimens for the first-line treatment of adults with HER2+ unresectable locally advanced or metastatic GEA: Ziihera plus tislelizumab and fluoropyrimidine- and platinum-containing chemotherapy for adults with HER2+ IHC 3+ or IHC 2+/ISH+ disease; and Ziihera plus fluoropyrimidine- and platinum-containing chemotherapy for adults with HER2+ IHC 3+ disease. The approval was based on results from the Phase 3 HERIZON-GEA-01 trial, which were first presented at ASCO GI 2026 , subsequently published in The New England Journal of Medicine and further evaluated through PD-L1 subgroup analyses presented at ASCO 2026.
The U.S . Prescribing Information for Ziihera contains Boxed Warnings for diarrhea and embryo-fetal toxicity.
Additional Important Safety Information related to Ziihera use in GEA is provided below. Please see full Prescription, including Boxed Warnings at https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf .
About the Phase 3 HERIZON-GEA-01 Trial HERIZON-GEA-01 ( NCT05152147 ) is a global, randomized, open-label Phase 3 trial, conducted jointly with BeOne Medicines, to evaluate and compare the efficacy and safety of zanidatamab plus chemotherapy, with and without tislelizumab, to trastuzumab plus chemotherapy as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 225 trial sites in more than 30 countries. Appropriate patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: zanidatamab in combination with chemotherapy and tislelizumab; zanidatamab in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial evaluated dual primary endpoints, PFS per blinded independent central review (BICR) and OS.
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. 5
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. 6
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. 6 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 6 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.
The FDA granted three Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC, one in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab for first-line HER2+ unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal GEA, and one for the treatment of adults with previously treated, locally advanced, unresectable, or metastatic HER2+ colorectal cancer (CRC). The FDA also granted 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, gastric (including GEJ) cancer, and esophageal cancer, as well as Orphan Drug designations from the European Medicines Agency for the treatment of BTC, gastric/gastroesophageal junction cancer, and esophageal cancer. Jazz continues to pursue additional regulatory approvals for zanidatamab in markets worldwide.
Important Safety Information for ZIIHERA
WARNING: DIARRHEA and EMBRYO-FETAL TOXICITY
ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, can cause severe diarrhea, including life threatening and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated. Interrupt, reduce the dose or discontinue ZIIHERA based on severity.
Embryo-Fetal Toxicity: Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
Diarrhea: ZIIHERA can cause severe diarrhea.
When ZIIHERA is used in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr, severe, life threatening, and fatal cases of diarrhea can occur despite loperamide prophylaxis. The risk of severe and life threatening diarrhea is higher when ZIIHERA is administered with chemotherapy and tislelizumab-jsgr, with a higher risk in patients aged ≥ 65 years compared to younger patients. Advise patients to increase oral fluids, begin antidiarrheals, and notify their healthcare provider immediately if diarrhea occurs .
Administer antidiarrheal prophylaxis with loperamide in cycle 1 for all patients receiving ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr. Begin loperamide at the first loose stool when ZIIHERA is administered in combination with chemotherapy. Administer fluids, electrolytes, and additional antidiarrheal agents as necessary. Before modifying the dose of ZIIHERA, evaluate, modify or discontinue drug(s) contributing to diarrhea in accordance with their respective prescribing information. Withhold, reduce the dose, or permanently discontinue ZIIHERA based on severity.
If treating patients with ZIIHERA in combination with FOLFOX, do not administer the fluorouracil bolus.
ZIIHERA in combination with chemotherapy and tislelizumab-jsgr
Diarrhea was reported in 85% of 330 patients in clinical studies, including Grade 4 (2.1%), Grade 3 (24%), and Grade 2 (31%) events. Fatal outcomes resulting from diarrhea occurred in 1.5% of patients. Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 3.9% of patients.
In cycle 1, diarrhea at Grade 4 severity occurred in 1.5% and Grade 3 severity occurred in 15% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days.
ZIIHERA in combination with chemotherapy
Diarrhea was reported in 81% of 395 patients in clinical studies, including Grade 4 (1.3%), Grade 3 (20%) and Grade 2 (33%). Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 1.8% of patients.
In cycle 1, diarrhea at Grade 4 severity occurred in 0.8% and Grade 3 severity occurred in 14% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days.
Embryo-Fetal Toxicity: Based on the mechanism of action, ZIIHERA can cause fetal harm when administered to a pregnant woman. There are no human or animal data on the use of ZIIHERA in pregnancy. 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 while receiving ZIIHERA and for 4 months following the last dose of ZIIHERA.
Left Ventricular Dysfunction (LVD): ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF).
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 < 50%.
ZIIHERA in combination with chemotherapy and tislelizumab-jsgr
LVEF decrease (an absolute decline in LVEF of > 10%, resulting in a final value of < 50%) was observed in 9% of 330 patients in clinical studies. LVD leading to permanent discontinuation of ZIIHERA was reported in 3% of patients. Fatal outcomes due to LVD occurred in one patient (0.3%). The median time to first occurrence of LVD was 6.9 months (range: 1.2 to 29.1 months). LVD resolved in 78% of patients.
ZIIHERA in combination with chemotherapy
LVEF decrease was observed in 5% of 395 patients. LVD leading to permanent discontinuation of ZIIHERA was reported in 1.0% of patients. The median time to first occurrence of LVD was 6.0 months (range: 1.4 to 15.0 months). LVD dysfunction resolved in 70% of patients. Infusion-Related Reactions: ZIIHERA can cause infusion-related reactions (IRRs).
Prior to each dose of ZIIHERA, administer premedication 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.
ZIIHERA in combination with chemotherapy and tislelizumab-jsgr
An IRR was reported in 22% of 330 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.2%), and Grade 2 (16%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.3% of patients. IRRs occurred on the first day of dosing in 17% of patients. Of all patients who experienced IRRs, 60% of reactions resolved within the first day.
ZIIHERA in combination with chemotherapy
An IRR was reported in 24% of 395 patients in clinical studies, including Grade 4 (0.3%), Grade 3 (1.5%), and Grade 2 (18%) despite use of prophylaxis. IRRs leading to permanent discontinuation of ZIIHERA were reported in 1.3% of patients. IRRs occurred on the first day of dosing in 22% of patients. Of all patients who experienced IRRs, 83% of reactions resolved within the first day.
Adverse Reactions
ZIIHERA in combination with chemotherapy and tislelizumab-jsgr
Serious adverse reactions occurred in 59% of 294 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (17%), IRR (5%), vomiting (4.8%), hypokalemia (4.4%), acute kidney injury (3.7%), pneumonia (3.7%), nausea (2.4%), decreased appetite (2.4%), and anemia (2.4%). Fatal adverse reactions occurred in 2.4% of patients and included acute kidney injury (N=2), cardiac failure, diarrhea, dehydration, hypovolemic shock and intestinal obstruction (all N=1).
Permanent discontinuation of ZIIHERA occurred in 13% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included diarrhea (4.4%) and ejection fraction decreased (2.7%).
The most common adverse reactions (≥ 20%) were diarrhea (83%), nausea (56%), decreased appetite (46%), vomiting (44%), hypokalemia (39%), fatigue (37%), rash (36%), peripheral neuropathy (27%), and IRR (25%).
ZIIHERA in combination with chemotherapy
Serious adverse reactions occurred in 49% of 305 patients in HERIZON-GEA-01. Serious adverse reactions in > 2% of patients included diarrhea (11%), vomiting (3.3%), decreased appetite (2.6%), pneumonia (2.6%), sepsis (2.6%), hypokalemia (2.3%), and nausea (2.3%).
Permanent discontinuation of ZIIHERA occurred in 10% of patients. Adverse reactions that resulted in permanent discontinuation of ZIIHERA in ≥ 1% of patients included ejection fraction decreased (2.0%), IRR (1.6%), and diarrhea (1.6%).
The most common adverse reactions (≥ 20%) were diarrhea (79%), nausea (54%), vomiting (44%), decreased appetite (40%), fatigue (36%), hypokalemia (33%), peripheral neuropathy (32%), IRR (25%), and rash (22%).
Pediatric Use: Safety and efficacy of ZIIHERA have not been established in pediatric patients.
Geriatric Use
ZIIHERA in combination with chemotherapy and tislelizumab-jsgr
Of 302 patients randomized to ZIIHERA in combination with chemotherapy and tislelizumab-jsgr in HERIZON-GEA-01, there were 139 (46%) patients aged ≥ 65 years. One hundred and six (35%) were aged 65-74 years and 33 (11%) were aged ≥ 75 years.
There was a higher incidence of Grade ≥ 3 adverse reactions observed in patients aged ≥ 65 years (87%) as compared to younger patients (80%). The incidence of Grade 3 or 4 diarrhea was higher in patients aged ≥ 65 years (32%) compared to younger patients (20%).
There was an increased incidence of fatal adverse reactions in patients aged ≥ 65 years (4.4%); including acute kidney injury (N=2), cardiac failure, dehydration, hypovolemic shock and intestinal obstruction (all N=1), compared to younger patients (0.6%), including diarrhea (N=1).
ZIIHERA in combination with chemotherapy
Of 304 patients randomized to ZIIHERA in combination with chemotherapy in HERIZON-GEA-01, there were 130 (43%) patients aged ≥ 65 years. One hundred (33%) were aged 65-74 years and 30 (10%) were aged ≥ 75 years.
No overall differences in safety were observed between patients aged ≥ 65 years and younger adult patients.
® TEVIMBRA (tislelizumab) is a registered trademark of BeOne Medicines.
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. Please visit www.jazzpharmaceuticals.com for more information.
Cautionary Note Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to the potential therapeutic and differentiated clinical benefits of Ziihera and of combination therapies with Ziihera, including Ziihera's potential to extend survival, Ziihera's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the successful completion of regulatory activities and uncertain regulatory approval, risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals' Securities and Exchange Commission filings and reports, including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2025 and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made.
Contacts:
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1 Bray F., et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians . 2024 April; doi.org/10.3322/caac.21834Digital Object Identifier (DOI). 2 Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625. 3 Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484. 4 Stroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249. 5 Tabernero J., et al. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Taylor & Francis . 2022 July; doi.org/10.2217/fon-2022-0595 . 6 ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA : Jazz Pharmaceuticals, Inc.