ZIIHERA
Generic: ZANIDATAMAB-HRII
Basic Information
Manufacturer
Jazz Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
ae5d9425-fae5-4541-a158-150998343348
Indications & Usage
1 INDICATIONS AND USAGE 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 )] .
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
ZIIHERA is a bispecific HER2-directed antibody 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 ) 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).
( 1 )
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] .
Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
ZIIHERA is a bispecific HER2-directed antibody 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 ) 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).
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS 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.
Biliary Tract Cancer The safety of ZIIHERA was evaluated in 80 patients with previously treated, unresectable or metastatic HER2-positive biliary tract cancer who received at least one prior gemcitabine-containing chemotherapy regimen in HERIZON‑BTC‑01 [See Clinical Studies ( 14 )].
Patients received ZIIHERA 20 mg/kg by IV infusion once every 2 weeks until disease progression or unacceptable toxicity.
The median duration of exposure to ZIIHERA was 5.6 months (range: 0.5 to 27.2 months).
Serious adverse reactions occurred in 53% of patients 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.
Permanent discontinuation due to an adverse reaction occurred in 2.5% of patients who received ZIIHERA.
Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients who received ZIIHERA included decreased ejection fraction and pneumonitis.
Dosage interruptions due to an adverse reaction, excluding temporary interruptions of ZIIHERA infusions due to infusion-related reactions, occurred in 41% of patients who received ZIIHERA.
The most frequent adverse reactions (> 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 potassium.
Dosage reductions due to an adverse reaction occurred in 4% of patients who received ZIIHERA.
Adverse reactions requiring dosage reductions in > 1% of patients were diarrhea, nausea, and decreased weight.
The most common adverse reactions in patients receiving ZIIHERA (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue.
Table 3 summarizes the adverse reactions that occurred in HERIZON‑BTC‑01.
Table 3: Adverse Reactions (≥ 15%) in Patients with Unresectable or Metastatic HER2-Positive BTC Receiving ZIIHERA in HERIZON-BTC-01 Adverse Reaction* ZIIHERA N=80 All Grades (%) Grades 3 or 4 (%) Gastrointestinal disorders Diarrhea a 50 10 Abdominal pain b 29 1 Nausea 18 1 Vomiting 15 1 Injury, poisoning and procedural complications Infusion-related reaction 35 1 General disorders and administration site conditions Fatigue c 24 4 Skin and subcutaneous tissue disorders Rash d 19 0 Metabolism and nutrition disorders Decreased appetite 16 0 * Graded per CTCAE version 5.
a Diarrhea includes diarrhea and enteritis b Abdominal pain includes abdominal pain and abdominal pain upper c Fatigue includes asthenia and fatigue d Rash includes dermatitis, dermatitis acneiform, palmar-plantar erythrodysaesthesia syndrome, rash, rash maculo-papular, and rash pustular Table 4 summarizes the laboratory abnormalities in HERIZON‑BTC‑01.
Table 4: Laboratory Abnormalities (≥ 30%) that Worsened from Baseline in Patients with Unresectable or Metastatic HER2-Positive BTC Receiving ZIIHERA in HERIZON-BTC-01 Laboratory Abnormalities ZIIHERA* All Grades (%) Grades 3 or 4 (%) Hematology Hemoglobin decreased 88 14 Lymphocytes decreased 44 8 Chemistry Lactate dehydrogenase increased 55 0 Albumin decreased 53 0 Aspartate aminotransferase increased 47 10 Alanine aminotransferase increased 46 8 Alkaline phosphatase increased 41 5 Sodium decreased 35 10 Potassium decreased 34 5 *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.
( 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.
Biliary Tract Cancer The safety of ZIIHERA was evaluated in 80 patients with previously treated, unresectable or metastatic HER2-positive biliary tract cancer who received at least one prior gemcitabine-containing chemotherapy regimen in HERIZON‑BTC‑01 [See Clinical Studies ( 14 )].
Patients received ZIIHERA 20 mg/kg by IV infusion once every 2 weeks until disease progression or unacceptable toxicity.
The median duration of exposure to ZIIHERA was 5.6 months (range: 0.5 to 27.2 months).
Serious adverse reactions occurred in 53% of patients 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.
Permanent discontinuation due to an adverse reaction occurred in 2.5% of patients who received ZIIHERA.
Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients who received ZIIHERA included decreased ejection fraction and pneumonitis.
Dosage interruptions due to an adverse reaction, excluding temporary interruptions of ZIIHERA infusions due to infusion-related reactions, occurred in 41% of patients who received ZIIHERA.
The most frequent adverse reactions (> 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 potassium.
Dosage reductions due to an adverse reaction occurred in 4% of patients who received ZIIHERA.
Adverse reactions requiring dosage reductions in > 1% of patients were diarrhea, nausea, and decreased weight.
The most common adverse reactions in patients receiving ZIIHERA (≥ 20%) were diarrhea, infusion-related reaction, abdominal pain, and fatigue.
Table 3 summarizes the adverse reactions that occurred in HERIZON‑BTC‑01.
Table 3: Adverse Reactions (≥ 15%) in Patients with Unresectable or Metastatic HER2-Positive BTC Receiving ZIIHERA in HERIZON-BTC-01 Adverse Reaction* ZIIHERA N=80 All Grades (%) Grades 3 or 4 (%) Gastrointestinal disorders Diarrhea a 50 10 Abdominal pain b 29 1 Nausea 18 1 Vomiting 15 1 Injury, poisoning and procedural complications Infusion-related reaction 35 1 General disorders and administration site conditions Fatigue c 24 4 Skin and subcutaneous tissue disorders Rash d 19 0 Metabolism and nutrition disorders Decreased appetite 16 0 * Graded per CTCAE version 5.
a Diarrhea includes diarrhea and enteritis b Abdominal pain includes abdominal pain and abdominal pain upper c Fatigue includes asthenia and fatigue d Rash includes dermatitis, dermatitis acneiform, palmar-plantar erythrodysaesthesia syndrome, rash, rash maculo-papular, and rash pustular Table 4 summarizes the laboratory abnormalities in HERIZON‑BTC‑01.
Table 4: Laboratory Abnormalities (≥ 30%) that Worsened from Baseline in Patients with Unresectable or Metastatic HER2-Positive BTC Receiving ZIIHERA in HERIZON-BTC-01 Laboratory Abnormalities ZIIHERA* All Grades (%) Grades 3 or 4 (%) Hematology Hemoglobin decreased 88 14 Lymphocytes decreased 44 8 Chemistry Lactate dehydrogenase increased 55 0 Albumin decreased 53 0 Aspartate aminotransferase increased 47 10 Alanine aminotransferase increased 46 8 Alkaline phosphatase increased 41 5 Sodium decreased 35 10 Potassium decreased 34 5 *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.