Overview
11 DESCRIPTION Zanidatamab‑hrii is a humanized, IgG-like, bispecific HER2-directed antibody. Zanidatamab‑hrii is produced in Chinese hamster ovary cells via recombinant DNA technology and has a molecular weight of 124.8 kDa. ZIIHERA (zanidatamab‑hrii) for injection is supplied as a sterile, preservative free, white lyophilized powder that requires reconstitution and dilution for intravenous use.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 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. 12.2 Pharmacodynamics Zanidatamab‑hrii exposure-response relationships and the time course of the pharmacodynamic response are unknown. Cardiac Electrophysiology A mean increase in the QTc interval > 20 ms was not observed at the recommended approved dosage.
Indications
- 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).
Common Doses
- 20 mg
- 15 mg
- 300 mg
- 5.7 mL
Dosage
2 DOSAGE AND ADMINISTRATION • 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 )] .
Black Box Warning
WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.3 )] . WARNING: EMBRYO‑FETAL TOXICITY See full prescribing information for complete boxed warning. • Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception. ( 5.1 )
Contraindications
- 4 CONTRAINDICATIONS None. • None. ( 4 )
Side Effects
- 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.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.