Zanidatamab

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 of the receptor on the tumor cell surface.

• 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 [see Dosage and Administration ( 2.1 )]. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] .

• None. • None.contraindicated

• Premedicate patients with acetaminophen, an antihistamine and a corticosteroid, 30‑60 minutes prior to each administration of ZIIHERA infusion to prevent potential infusion-related reactions (IRRs). ( 2.2 ) • The recommended dosage of ZIIHERA is 20 mg/kg given as an intravenous infusion once every 2 weeks. ( 2.3 ) 2.1 Patient Selection Select patients for treatment of unresectable or metastatic biliary tract cancer based on HER2-positive (IHC 3+) tumor specimens, as detected by an FDA-approved test [see Clinical Studies ( 14 )] . Information on FDA-approved tests for HER2 protein expression in biliary tract cancers is available at: http://www.fda.gov/CompanionDiagnostics . 2.2 Premedications Premedicate all patients 30 to 60 minutes prior to each dose of ZIIHERA to reduce the risk of infusion-related reactions [see Warnings and Precautions ( 5.3 )] : • Administer acetaminophen, an antihistamine (such as diphenhydramine) and a corticosteroid (such as hydrocortisone). 2.3 Recommended Dosage Recommended Dosage and Administration The recommended dosage of ZIIHERA is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until disease progression or unacceptable toxicity. Missed dose If a planned dose of ZIIHERA is delayed or missed, administer the dose as soon as possible; do not wait until the next planned dose. Adjust the administration schedule to maintain a 2-week interval between doses. 2.4 Dosage Modifications for Adverse Reactions • The recommended dosage reduction of ZIIHERA for adverse reactions is 15 mg/kg as described in Table 1 .

• Left Ventricular Dysfunction: Assess left ventricular ejection fraction (LVEF) prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold or permanently discontinue ZIIHERA based on severity. ( 2.4 , 5.2 ) • Infusion-Related Reactions (IRRs): Premedicate before each infusion of ZIIHERA. Interrupt the infusion, decrease the infusion rate, and/or permanently discontinue ZIIHERA based on severity. ( 2.4 , 5.3 ) • Diarrhea: ZIIHERA can cause severe diarrhea. Administer antidiarrheal treatment as clinically indicated. Withhold or permanently discontinue ZIIHERA based on severity. ( 2.4 , 5.4 ) 5.1 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. 5.2 Left Ventricular Dysfunction ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF).

The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Embyro-Fetal Toxicity [see Warnings and Precautions ( 5.1 )] • Left Ventricular dysfunction [see Warnings and Precautions ( 5.2 )] • Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] • Diarrhea [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (≥ 20%) are diarrhea, infusion-related reaction, abdominal pain, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1‑800‑520‑5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population of ZIIHERA described in WARNINGS AND PRECAUTIONS reflect exposure in 233 patients administered ZIIHERA 20 mg/kg intravenously as a single agent in two single-arm, open-label studies (ZWI‑ZW25‑101 and HERIZON‑BTC‑01), which enrolled 109 patients with biliary tract cancer, and 124 patients with other cancers. Among 233 patients who received ZIIHERA, 39% were exposed for 6 months or longer, and 17% were exposed for greater than one year.

• Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of ZIIHERA. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on 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. Use of ZIIHERA is not recommended during pregnancy (see CLINICAL CONSIDERATIONS). Advise patients of potential risks to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received ZIIHERA during pregnancy or within 4 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with local standard of care.

Metabolism

Zanidatamab‑hrii PK parameters are presented as means (percent coefficient of variation) following administration of ZIIHERA 20 mg/kg every 2 weeks after the 7 th or later dose unless otherwise indicated. Zanidatamab‑hrii maximum concentration (C max ) is 600 (22.2) µg/mL, the lowest measured concentration (C trough ) is 178 (29.6) µg/mL, and total systemic exposure (AUC 0-336h ) is 3,976 (22.5) days*µg/mL following administration of ZIIHERA.

• Nov 20, 2024BLABLA761416Jazz Pharms

1. 1Chills716%
2. 2Off Label Use716%
3. 3Infusion Related Reaction614%
4. 4Diarrhoea511%
5. 5Pyrexia36.8%
6. 6Acute Kidney Injury24.5%
7. 7Arthralgia24.5%
8. 8Disease Progression24.5%
9. 9Ejection Fraction Decreased24.5%
10. 10Hyperpyrexia24.5%
11. 11Pneumonitis24.5%
12. 12Arrhythmia12.3%
13. 13Blood Pressure Increased12.3%
14. 14Cardiac Arrest12.3%
15. 15Cardiac Failure12.3%

The 10 most recently updated of 31 ClinicalTrials.gov registrations naming Zanidatamab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors
  Recruiting · Phase 2 · Interventional · 200 enrolled · Jazz Pharmaceuticals
  NCT06695845updated 2026-06-09
• Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Postive Advanced Gastroesophageal Adenocarcinoma
  Recruiting · Phase 2 · Interventional · 168 enrolled · Canadian Cancer Trials Group
  NCT06043427updated 2026-06-09
• An Exploratory Study of Zanidatamab in HER2-positive Advanced Tumor After at Least One Line of Standard Therapy
  Not yet recruiting · Phase 2 · Interventional · 10 enrolled · Haihua Yuan
  NCT07631871updated 2026-06-08
• A Phase 2 Single-Arm Open-Label Pilot Trial Evaluating Zanidatamab (ZW25) in Patients With Early Stage HER2/Neu Positive (HER2+) Breast Cancer (BC)
  Recruiting · Phase 2 · Interventional · 20 enrolled · M.D. Anderson Cancer Center
  NCT05035836updated 2026-06-05
• A Phase 1/1b Study of IAM1363 in HER2 Cancers
  Recruiting · Phase 1 · Interventional · 383 enrolled · Iambic Therapeutics, Inc
  NCT06253871updated 2026-06-04
• Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies
  Completed · Phase 3 · Interventional · 404 enrolled · BeOne Medicines
  NCT04164199updated 2026-06-03
• Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
  Recruiting · Phase 1 · Phase 2 · Interventional · 768 enrolled · Boehringer Ingelheim
  NCT06324357updated 2026-05-26
• A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers
  Active not recruiting · Phase 3 · Interventional · 920 enrolled · Jazz Pharmaceuticals
  NCT05152147updated 2026-05-19
• Personalized Medicine for Advanced Biliary Cancer Patients
  Recruiting · Phase 3 · Interventional · 800 enrolled · UNICANCER
  NCT05615818updated 2026-05-19
• Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer
  Recruiting · Phase 3 · Interventional · 286 enrolled · Jazz Pharmaceuticals
  NCT06282575updated 2026-05-11

Frequently asked questions

How does Zanidatamab work?

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 of the receptor on the tumor cell surface.

What is Zanidatamab used for?

According to FDA labeling, Zanidatamab carries indications including: 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 [see Dosage and Administration ( 2.1 )]. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Zanidatamab?

Zanidatamab is classified as HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors, Bispecific HER2-directed Antibody, Antibody-Receptor Interactions, HER2-directed Antibody Interactions, Cellular Growth Phase Reduction, Increased Cellular Death.

What are the brand names for Zanidatamab?

Zanidatamab is marketed under brand names including Ziihera.

What are the contraindications for Zanidatamab?

Zanidatamab labeling lists contraindications including: None. • None.. Always consult the full prescribing information and a clinician.