Tislelizumab

Prescription Drug User Fee Act (PDUFA) date set for August 25, 2026 For U.S. media and investors only DUBLIN, April 27, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the U.S. Food and Drug Administration (FDA) accepted for filing with Priority Review the supplemental Biologics License Application (sBLA) for Ziihera® (zanidatamab-hrii) containing combinations for the first-line treatment of adult patients with HER2-positive (HER2+) unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or gastroesophageal adenocarcinoma (GEA). The FDA has set a PDUFA target action date of August 25, 2026. The sBLA is supported by data from the pivotal HERIZON-GEA-01 trial to investigate the efficacy and safety of zanidatamab in combination with standard-of-care chemotherapy with or without the PD-1 inhibitor Tevimbra® (tislelizumab) in patients with advanced or metastatic GEA, including gastric, GEJ and esophageal adenocarcinomas. The submission is under review via the Real-Time Oncology Review (RTOR) program, an initiative of FDA's Oncology Center of Excellence designed to provide a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. "The HERIZON-GEA-01 trial results are practice changing, supporting the potential of zanidatamab as the HER2-targeted agent-of-choice in HER2+ first-line locally advanced or metastatic GEA. Importantly, the results demonstrated adding tislelizumab to zanidatamab plus chemotherapy further enhanced clinical benefit and marked the first immuno-oncology combination to show efficacy across both PD-L1–positive and PD-L1–negative tumors in this clinical setting," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of R&D, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to work closely with FDA to obtain approval and quickly bring zanidatamab to market for GEA patients in need of new options." The FDA granted Breakthrough Therapy designation to zanidatamab in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab, for the first-line treatment of patients with HER2+ unresectable locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Breakthrough Therapy designation is intended to expedite the development and review of therapies that, based on preliminary clinical evidence, may offer substantial improvement over available therapies on one or more clinically significant endpoints, reflecting both the seriousness of the disease and the unmet medical need in this setting. 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 or 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 300 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 is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS. Results from the trial were presented in January 2026 at the 2026 ASCO Gastrointestinal Cancers Symposium. 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 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.4 About Ziihera ® (zanidatamab-hrii) 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 tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.5 In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.1 The 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).1 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 under license agreements from Zymeworks, which first developed the molecule. An sBLA for zanidatamab is being reviewed by the FDA under RTOR in first-line HER2+ locally advanced or metastatic GEA. The FDA granted two Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC, and one in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab for first-line HER2+ unresectable locally advanced or metastatic gastric, GEJ or esophageal adenocarcinoma. 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/GEJ cancer and oesophageal 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: ® 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 potentially life-changing medicines for people with rare disease — often with limited or no therapeutic options. We have a diverse portfolio of marketed 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 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 benefits of Ziihera (zanidatamab-hrii) and of combination therapies with zanidatamab, zanidatamab's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers, expected timing of and ability to obtain FDA approval under the RTOR program for zanidatamab in HER2+ first-line GEA 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: Media: [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Investor: [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 1Abrahao-Machado I.F., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625. 2Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484. 3Stroes, 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. 4Battaglin F, et al. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell International. 2018;18(99). 5ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. SOURCE Jazz Pharmaceuticals plc 21% more press release views with Request a Demo

Rapid oral presentation of PD-L1 subgroup data from HERIZON-GEA-01 evaluating zanidatamab combinations, and additional analyses of tolerability, biomarker response and real-world treatment patterns in HER2+ GEA For U.S. media and investors only DUBLIN, April 21, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the Company and its partners will present three rapid oral and seven poster presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place from May 29-June 2, 2026, in Chicago. The data reflect Jazz's continued momentum in oncology and the Company's focus on advancing treatment approaches in difficult-to-treat cancers through late-stage clinical research, real-world evidence and ongoing pipeline innovation. Key ASCO 2026 presentations include: Data 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) in previously untreated HER2-positive (HER2+) gastroesophageal adenocarcinoma (GEA), including a rapid oral presentation of analyses of progression-free survival (PFS) and overall survival (OS) across PD-L1 subgroups, as well as analyses of the characterization and management of gastrointestinal adverse events. Analyses from the Phase 3 IMforte trial evaluating Zepzelca® (lurbinectedin) plus atezolizumab (Tecentriq®) as first-line maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC), including quality-adjusted time without symptoms or toxicity, as well as a rapid oral presentation on outcomes across SCLC molecular subtypes. "Building on the strength of the HERIZON-GEA-01 trial results, additional analyses being presented at ASCO will provide further details on the impact of zanidatamab in HER2+ GEA, including across PD-L1 subgroups. These data will continue to inform treatment decision-making and enable the successful treatment integration of zanidatamab in clinical practice," 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. "Together with additional analyses of Zepzelca from the Phase 3 IMforte study in first-line maintenance extensive-stage small cell lung cancer and progress in our pipeline, these data reflect our growing and increasingly differentiated oncology portfolio, as well as our commitment to advancing innovative approaches for patients facing some of the most difficult-to-treat cancers." The ASCO abstracts are available at: The full list of Jazz- and partner-supported presentations at the 2026 ASCO Annual Meeting are: Zanidatamab Presentations: Lurbinectedin Presentations: About Ziihera® (zanidatamab-hrii) 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 tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.[1] In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.1 The 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).1 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.   A supplemental biologics license application for zanidatamab was submitted to the FDA under Real-Time Oncology Review in first-line HER2+ locally advanced or metastatic GEA. The FDA granted two Breakthrough Therapy designations for zanidatamab's development: one as a single agent for previously treated HER2 gene-amplified BTC, and 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 adenocarcinoma. 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 oesophageal 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: About Zepzelca® (lurbinectedin) Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and potentially cell death.2 In October 2025, the FDA approved Zepzelca in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, as maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. In June 2020, the FDA approved Zepzelca under accelerated approval for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information for ZEPZELCA Myelosuppression ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia. Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3. To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF). Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ZEPZELCA with Intravenous Atezolizumab In the IMforte study, primary prophylaxis of G-CSF was administered to 84% of patients. Based on laboratory values, decreased neutrophils occurred in 36%, including 18% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased neutrophil cells was 31 days and a median duration of 10 days. Febrile neutropenia occurred in 1.7%. Sepsis occurred in 1%. There were 7 fatal infections: pneumonia (n=3), sepsis (n=3), and febrile neutropenia (n=1). Based on laboratory values, decreased platelets occurred in 54%, including 15% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased platelet cells was 31 days and a median duration of 12 days. Based on laboratory values, decreased hemoglobin occurred in 51%, including 13% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased hemoglobin was 64 days and a median duration of 8 days. ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients. Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients. Hepatotoxicity ZEPZELCA can cause hepatotoxicity which may be severe. Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity. ZEPZELCA with Intravenous Atezolizumab In the IMforte study, based on laboratory values, increased alanine aminotransferase (ALT) occurred in 25%, including 3% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. Increased aspartate aminotransferase (AST) occurred in 24% including 3% Grade 3 or Grade 4. The median time to onset of Grade ≥3 elevation in transaminases was 52 days (range: 6 to 337). ZEPZELCA as a Single Agent In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 elevations of ALT and AST were observed in 6% and 3% of patients, respectively, and Grade 4 elevations of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The median time to onset of Grade ≥3 elevation in transaminases was 8 days (range: 3 to 49), with a median duration of 7 days. Extravasation Resulting in Tissue Necrosis Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary. ZEPZELCA with Intravenous Atezolizumab In the IMforte study, extravasation resulting in skin necrosis occurred in one patient who received ZEPZELCA in combination with atezolizumab. Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation. Rhabdomyolysis Rhabdomyolysis has been reported in patients treated with ZEPZELCA. Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity. ZEPZELCA with Intravenous Atezolizumab In the IMforte study, among 235 patients who had a creatine phosphokinase laboratory evaluation, increased creatine phosphokinase occurred in 9% who received ZEPZELCA in combination with atezolizumab. Embryo-Fetal Toxicity ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose. Lactation There are no data on the presence of ZEPZELCA in human milk, however, because of the potential for serious adverse reactions from ZEPZELCA in breastfed children, advise women not to breastfeed during treatment with ZEPZELCA and for 2 weeks after the last dose. ADVERSE REACTIONS ZEPZELCA with Intravenous Atezolizumab Serious adverse reactions occurred in 31% of patients receiving ZEPZELCA in combination with atezolizumab. Serious adverse reactions occurring in >2% were pneumonia (2.5%), respiratory tract infections (2.1%), dyspnea (2.1%), and decreased platelet count (2.1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab including pneumonia (3 patients), sepsis (3 patients), cardio-respiratory arrest (2 patients), myocardial infarction (2 patients), and febrile neutropenia (1 patient). The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes (55%), decreased platelets (54%), decreased hemoglobin (51%), decreased neutrophils (36%), nausea (36%), and fatigue/asthenia (32%). ZEPZELCA as a Single Agent Serious adverse reactions occurred in 34% of patients who received ZEPZELCA. Serious adverse reactions in ≥3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia. The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia (79%), lymphopenia (79%), fatigue (77%), anemia (74%), neutropenia (71%), increased creatinine (69%), increased alanine aminotransferase (66%), increased glucose (52%), thrombocytopenia (37%), nausea (37%), decreased appetite (33%), musculoskeletal pain (33%), decreased albumin (32%), constipation (31%), dyspnea (31%), decreased sodium (31%), increased aspartate aminotransferase (26%), vomiting (22%), decreased magnesium (22%), cough (20%), and diarrhea (20%). DRUG INTERACTIONS Effect of CYP3A Inhibitors and Inducers Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration cannot be avoided, reduce the ZEPZELCA dose as appropriate. Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA. GERIATRIC USE ZEPZELCA with Intravenous Atezolizumab Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was no overall difference in the incidence of serious adverse reactions in patients ≥65 years of age and patients <65 years of age (33% vs. 29%, respectively). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (45% vs. 31%, respectively). ZEPZELCA as a Single Agent Of the 105 patients with SCLC administered ZEPZELCA in clinical studies, 37 (35%) patients were 65 years of age and older, while 9 (9%) patients were 75 years of age and older. No overall difference in effectiveness was observed between patients aged 65 and older and younger patients. There was a higher incidence of serious adverse reactions in patients ≥65 years of age than in patients <65 years of age (49% vs. 26%, respectively). The serious adverse reactions most frequently reported in patients ≥65 years of age were related to myelosuppression and consisted of febrile neutropenia (11%), neutropenia (11%), thrombocytopenia (8%), and anemia (8%). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (76% vs. 50%, respectively). HEPATIC IMPAIRMENT Avoid administration of ZEPZELCA in patients with severe hepatic impairment. If administration cannot be avoided, reduce the dose. Monitor for increased adverse reactions in patients with severe hepatic impairment. Reduce the dose of ZEPZELCA in patients with moderate hepatic impairment. Monitor for increased adverse reactions in patients with moderate hepatic impairment. No dose adjustment of ZEPZELCA is recommended for patients with mild hepatic impairment. The full Prescribing Information for ZEPZELCA is available at: Tevimbra (tislelizumab) is a registered trademark of BeOne Medicines. Zepzelca a trademark of Pharma Mar, S.A. used by Jazz Pharmaceuticals under license. Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group. 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 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 benefits of zanidatamab in HER2+ first-line GEA, 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: Media Contact: [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Investor Contact: [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 1 ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2 ZEPZELCA (lurbinectedin) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. SOURCE Jazz Pharmaceuticals plc 21% more press release views with Request a Demo