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THE SAFETY PROFILE WAS ESTABLISHED ACROSS 80 PATIENTS IN HERIZON-BTC-011

ADVERSE REACTIONS (≥15%) IN PATIENTS RECEIVING ZIIHERA (N=80)1*

Adverse ReactionsZIIHERA
 All Grades (%)Grades 3-4 (%)
Gastrointestinal disorders
Diarrhea†5010
Abdominal pain‡291
Nausea181
Vomiting151
Injury, poisoning, and procedural complications
IRR351
General disorders and administration site conditions
Fatigue§244
Skin and subcutaneous tissue disorders
Rash190
Metabolism and nutrition disorders
Decreased appetite160

*Analysis includes 18 patients with HER2 IHC 2+. ARs were graded per CTCAE v5.0.1

†Diarrhea includes diarrhea and enteritis.1

‡Abdominal pain includes abdominal pain and abdominal pain upper.1

§Fatigue includes asthenia and fatigue.1

Rash includes dermatitis, dermatitis acneiform, palmar-plantar erythrodysaesthesia syndrome, rash, rash maculo-papular, and rash pustular.1

  • Most common ARs (≥20%) are diarrhea, IRR, abdominal pain, and fatigue1
  • IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients1
  • Most IRRs resolved within 1 day1
  • SARs occurred in 53% of patients who received ZIIHERA. Those reported 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 ZIIHERA1
  • There were no reports of cytokine release syndrome2
  • ARs which resulted in permanent discontinuation in ≥1% of patients who received ZIIHERA included decreased ejection fraction and pneumonitis1
  • Dosage interruptions due to an AR, excluding temporary interruptions of ZIIHERA infusions due to IRRs, occurred in 41% of patients who received ZIIHERA. Most frequent ARs (>2% of patients) that required dosage interruption were diarrhea, increased alanine aminotransferase, increased aspartate aminotransferase, decreased ejection fraction, pneumonia, cholangitis, fatigue, biliary obstruction, abdominal pain, increased blood creatinine, and decreased potassium1
  • Dose reductions due to an AR occurred in 4% of patients who received ZIIHERA1
  • ARs requiring dosage reductions in >1% of patients were diarrhea, nausea, and decreased weight1

2.5% of patients who received ZIIHERA permanently discontinued treatment due to an AR1

AR=adverse reaction; CTCAE=Common Terminology Criteria for Adverse Events; HER2=human epidermal growth factor receptor 2; IHC=immunohistochemistry; IRR=infusion-related reaction; SAR=serious adverse reaction.

LABORATORY ABNORMALITIES

LABORATORY ABNORMALITIES (≥30%) THAT WORSENED FROM BASELINE IN PATIENTS RECEIVING ZIIHERA (N=80)1||#

Laboratory AbnormalitiesZIIHERA
 All Grades (%)Grades 3-4 (%)
Hematology
Hemoglobin decreased8814
Lymphocytes decreased448
Chemistry 
Lactate dehydrogenase increased 550
Albumin decreased 530
Aspartate aminotransferase increased 4710
Alanine aminotransferase increased 468
Alkaline phosphatase increased415
Sodium decreased3510
Potassium decreased 345

||Analysis includes 18 patients with HER2 IHC 2+.1

#The denominator used to calculate the rate varied from 78 to 80 based on the number of patients with a baseline value and at least one post-treatment value.1

 
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Dosing and Administration

INDICATION

ZIIHERA (zanidatamab-hrii) 50 mg/mL for Injection for IV 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.

This indication is approved under accelerated approval 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).

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

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.

Please click here to see the full Prescribing Information, including BOXED Warning.

References: 1. ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2024. 2. Data on file. Jazz Pharmaceuticals, Inc.