Bizengri Prescribing Information
Based on its mechanism of action, BIZENGRI 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 manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Animal studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose
Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman
Animal studies have demonstrated that HER2 and/or HER3 deficiency results in embryo-fetal malformation, including effects on cardiac, vascular and neuronal development, and embryolethality
Human IgG1 is known to cross the placenta; therefore, BIZENGRI has the potential to be transmitted from the mother to the developing fetus. Advise patients of the potential risk to a fetus.
There are clinical considerations if BIZENGRI is used in pregnant women, or if a patient becomes pregnant within 2 months after the last dose of BIZENGRI (
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Monitor women who received BIZENGRI during pregnancy or within 2 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care.
There are no available data on the use of BIZENGRI in pregnant women. In literature reports in pregnant women receiving a HER2-directed antibody, cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported. These case reports described oligohydramnios in pregnant women who received HER2-directed antibody alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after use of a HER2-directed antibody was stopped.
There were no animal reproductive or developmental toxicity studies conducted with zenocutuzumab-zbco. A literature-based assessment of the effects on reproduction demonstrated that HER2 and HER3 are critically important in embryo-fetal development. HER2 knockout mice or mice expressing catalytically inactive HER2 die at mid-gestation due to cardiac dysfunction. HER2 knockout mice have also shown abnormal sympathetic nervous system development. In HER3-deficient mice, embryolethality occurred on embryonic day 13.5 due to cardiac and vascular defects, as well as abnormalities in other organs (neural crest, pancreas, stomach, and adrenal). In addition, HER3 is shown to be involved in mammary gland ductal morphogenesis in mice. Zenocutuzumab-zbco can cause embryo-fetal toxicity based on its mechanism of action.
BIZENGRI can cause fetal harm when administered to a pregnant woman
Verify the pregnancy status of females of reproductive potential prior to initiating BIZENGRI
Advise female patients of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.
BIZENGRI® is a bispecific HER2- and HER3-directed antibody indicated for the treatment of:
- Adults with advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.* ()
1.1 Advanced Unresectable or MetastaticNRG1Fusion-Positive Non-Small Cell Lung CancerBIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (
NRG1) gene fusion with disease progression on or after prior systemic therapy.This indication is approved under accelerated approval based on overall response rate and duration of response
[see Clinical Studies ].Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). - Adults with advanced, unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.* ()
1.2 Advanced Unresectable or MetastaticNRG1Fusion-Positive Pancreatic AdenocarcinomaBIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (
NRG1) gene fusion with disease progression on or after prior systemic therapy.This indication is approved under accelerated approval based on overall response rate and duration of response
[see Clinical Studies ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
*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).
- Select patients for treatment with BIZENGRI based on the presence of an NRG1gene fusion. ()
2.1 Patient SelectionSelect patients for treatment with BIZENGRI based on the presence of an
NRG1gene fusion in tumor specimens[see Clinical Studies ].An FDA-approved test for the detection of
NRG1gene fusions is not currently available. - Evaluate left ventricular ejection fraction (LVEF) before initiating BIZENGRI. ()
2.2 Recommended Evaluation Before Initiating BIZENGRIBefore initiating BIZENGRI, evaluate left ventricular ejection fraction (LVEF)
[see Warnings and Precautions ]. - The recommended dosage of BIZENGRI is 750 mg every 2 weeks until disease progression or unacceptable toxicity. ()
2.3 Recommended Dosage- The recommended dosage of BIZENGRI is 750 mg as an intravenous (IV) infusion every 2 weeks until disease progression or unacceptable toxicity[see Dosage and Administration ].
- Administer premedications before each BIZENGRI infusion as recommended to reduce the risk of infusion-related reactions[see Dosage and Administration ].
- The recommended dosage of BIZENGRI is 750 mg as an intravenous (IV) infusion every 2 weeks until disease progression or unacceptable toxicity
- Administer premedications before each infusion to reduce the risk of infusion-related reactions. ()
2.4 Recommended PremedicationsPrior to each infusion of BIZENGRI, administer premedications to reduce the risk of infusion-related reactions (IRRs)
[see Warnings and Precautions ] (see Table 1).Table 1: Premedications Prior to BIZENGRI Infusions 1Optional after initial BIZENGRI infusion
MedicationDoseRoute of AdministrationCorticosteroid1 Dexamethasone (10 mg) Oral or intravenous Antipyretic Acetaminophen (1,000 mg) Oral or intravenous H1 Antihistamine Dexchlorpheniramine (5 mg)
or other anti-H1 equivalentIntravenous
or oral - Administer as an intravenous infusion, after dilution, over 4 hours. ()
2.7 Administration- If the infusion time exceeds the recommended storage time, the infusion bag must be discarded and a new infusion bag prepared to continue the infusion. Diluted BIZENGRI solution must by administered within:
- 6 hours from end of preparation of infusion solution stored at room temperature [15°C to 25°C (59°F to 77°F)]
- 28 hours from end of preparation of infusion solution stored refrigerated [2°C to 8°C (36°F to 46°F)]
- If the diluted BIZENGRI solution has been refrigerated, allow it to reach room temperature (approximately 30 minutes) prior to administration.
- Administer diluted BIZENGRI solution[see Dosage and Administration ]by intravenous infusion using an infusion set made of either PVC, polyethylene (PE), polyurethane (PUR) or polybutadiene (PB) with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.2 micrometer).
- Do not infuse BIZENGRI concomitantly in the same IV line with other agents.
- Administer BIZENGRI infusion via a peripheral or central line.
- Monitor patients closely for signs and symptoms of infusion-related reactions during BIZENGRI infusion and monitor patients for at least 1 hour following completion of the first BIZENGRI infusion and as clinically indicated[see Warnings and Precautions ].
- Administer intravenous infusion over 4 hours.
- If the infusion time exceeds the recommended storage time, the infusion bag must be discarded and a new infusion bag prepared to continue the infusion. Diluted BIZENGRI solution must by administered within:
Injection: 375 mg/18.75 mL (20 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial.
BIZENGRI can cause fetal harm when administered to a pregnant woman
Verify the pregnancy status of females of reproductive potential prior to initiating BIZENGRI
Advise female patients of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.
None.