Version July 2025
Exposure to zenocutuzumab during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.
Dosage guidance:
Safety: Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (Ref). Prior to the first infusion, premedicate with an antipyretic (eg, acetaminophen 1 g oral or IV), an H1 antihistamine (eg, dexchlorpheniramine 5 mg [or equivalent] oral or IV), and a corticosteroid (eg, dexamethasone 10 mg oral or IV). Prior to each subsequent infusion of zenocutuzumab, premedicate with an antipyretic and an H1 antihistamine to reduce the risk of infusion-related reactions; corticosteroid premedication is optional after the initial infusion.
Clinical considerations: Select patients for treatment with zenocutuzumab based on the presence of an NRG1 gene fusion in tumor specimens.
Non–small cell lung cancer, advanced, unresectable or metastatic, NRG1 fusion positive (previously treated): IV: 750 mg once every 2 weeks; continue until disease progression or unacceptable toxicity.
Pancreatic adenocarcinoma, advanced, unresectable or metastatic, NRG1 fusion positive (previously treated): IV: 750 mg once every 2 weeks; continue until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function prior to treatment initiation:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in zenocutuzumab pharmacokinetics in patients with CrCl 30 to 89 mL/minute.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect of severe kidney impairment on zenocutuzumab pharmacokinetics is unknown).
Liver impairment prior to treatment initiation:
Mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in zenocutuzumab pharmacokinetics in patients with mild hepatic impairment.
Moderate or severe (total bilirubin >1.5 times ULN and any AST) hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (effect of moderate or severe hepatic impairment on zenocutuzumab pharmacokinetics is unknown).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
No dose reduction is recommended for zenocutuzumab.
|
Adverse reaction |
Severity |
Zenocutuzumab dosage modification |
|---|---|---|
|
a LVEF = left ventricular ejection fraction; IRR = infusion-related reaction; ILD = interstitial lung disease. | ||
|
Cardiovascular toxicity: Left ventricular dysfunction |
LVEF 45% to 49% and absolute decrease from baseline ≥10% or LVEF <45% |
Interrupt zenocutuzumab; repeat LVEF assessment within 3 weeks. LVEF <45% or LVEF not recovered to within 10% from baseline: Permanently discontinue zenocutuzumab. LVEF ≥50% or LVEF 45% to 49% and recovered to within 10% of baseline: Resume zenocutuzumab. Monitor LVEF every 12 weeks while on treatment and as clinically indicated. |
|
Symptomatic heart failure |
Permanently discontinue zenocutuzumab. | |
|
Hypersensitivity reaction/IRR/anaphylactic reactions |
≤ Grade 3 IRR |
Interrupt zenocutuzumab infusion if IRR is suspected. Monitor patient until symptoms resolve and provide symptom management as needed. Resume infusion at 50% of the infusion rate at which the reaction occurred; may escalate infusion rate if there are no additional symptoms. Corticosteroid premedication may be used for subsequent infusions as necessary. |
|
Grade 4 IRR or any grade hypersensitivity or anaphylaxis |
Permanently discontinue zenocutuzumab. | |
|
Pulmonary toxicity: ILD/pneumonitis |
Grade 1 |
Consider prompt initiation of corticosteroids for suspected ILD/pneumonitis. Interrupt zenocutuzumab until recovery; resume treatment after resolution. |
|
≥ Grade 2 |
Promptly treat with corticosteroids. Permanently discontinue zenocutuzumab. | |
|
Other clinically relevant adverse reactions |
Grade 3 or 4 |
Provide symptomatic treatment as needed. Withhold zenocutuzumab until recovery to ≤ grade 1 or baseline; resume treatment after resolution of symptoms. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (11% to 13%)
Dermatologic: Skin rash (8% to 14%)
Endocrine & metabolic: Decreased serum albumin (26%), decreased serum magnesium (24% to 28%), decreased serum phosphate (26% to 31%), decreased serum potassium (21% to 26%), decreased serum sodium (28%)
Gastrointestinal: Abdominal distention (13%), abdominal pain (18%), constipation (15%), decreased appetite (5% to 11%), diarrhea (25% to 36%; grades 3/4: 2% to 5%), nausea (10% to 23%; grades 3/4: 1% to 5%), vomiting (8% to 23%; grades 3/4: 3%)
Hematologic & oncologic: Decreased hemoglobin (23% to 35%; grades 3/4: 4% to 10%), decreased platelet count (26%; grades 3/4: 10%), hemorrhage (13%; grades 3/4: 5%), leukopenia (21%; grades 3/4: 3%)
Hepatic: Increased gamma-glutamyl transferase (23%), increased serum alanine aminotransferase (30% to 51%), increased serum alkaline phosphatase (27% to 28%), increased serum aspartate aminotransferase (22% to 31%), increased serum bilirubin (31%)
Hypersensitivity: Infusion-related reaction (12% to 15%)
Nervous system: Fatigue (17% to 21%)
Neuromuscular & skeletal: Musculoskeletal pain (23% to 28%)
Respiratory: Cough (15%), dyspnea (18%)
1% to 10%:
Cardiovascular: Heart failure (2%)
Dermatologic: Xeroderma (10%)
Gastrointestinal: Stomatitis (7% to 10%)
Infection: Sepsis (1%)
Nervous system: Anxiety (10%)
Respiratory: Pneumonia (serious: 4%), pneumonitis (2%)
Miscellaneous: Fever (10%)
Frequency not defined:
Cardiovascular: Bradycardia, cardiac arrhythmia, carotid stenosis, decreased left ventricular ejection fraction, pericardial effusion, tachycardia
Dermatological: Cellulitis
Endocrine & metabolic: Dehydration
Gastrointestinal: Cholecystitis (acute), dysphagia, gastrointestinal obstruction, hemorrhoidal bleeding
Genitourinary: Urinary tract infection
Hematologic & oncologic: Lymphadenitis, myelodysplastic syndrome, neutropenia, prolonged partial thromboplastin time, tumor pain
Hepatic: Ascites, cholestatic jaundice, hepatic abscess
Infection: Staphylococcal infection, viral infection
Nervous system: Agitation, dizziness
Neuromuscular & skeletal: Back pain, bone fracture
Renal: Acute kidney injury, increased serum creatinine
Respiratory: Interstitial lung disease, pulmonary hypertension, upper respiratory tract infection
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiovascular toxicity: Zenocutuzumab can cause left ventricular dysfunction; left ventricular ejection fraction (LVEF) decreases have occurred with anti-HER2 therapies, including zenocutuzumab. In the clinical study, a small percentage of patients developed grade 2 LVEF decrease. Heart failure (without LVEF decrease), including fatal events, also occurred. Zenocutuzumab has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
• Hypersensitivity: Zenocutuzumab may cause serious and life-threatening infusion-related reactions (IRR), hypersensitivity, and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough. In the clinical study, a majority of IRR occurred during the first infusion and all events were grade 1 or 2. The median time to onset of IRR was 63 minutes (range: 13 to 240 minutes) from the start of infusion.
• Pulmonary toxicity: Serious and life-threatening interstitial lung disease and pneumonitis occurred in a small percentage of patients treated with zenocutuzumab, including grade 2 events resulting in permanent discontinuation.
Other warnings/precautions:
• Appropriate use: Select patients for treatment with zenocutuzumab based on the presence of an NRG1 gene fusion in tumor specimens.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Therapy Pack, Intravenous [preservative free]:
Bizengri (750 MG Dose): Zenocutuzumab-zbco 375 mg/18.75 mL (18.75 mL)
No
Soln Therapy Pack (Bizengri (750 MG Dose) Intravenous)
375MG/18.75ML (per mL): $760.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Administer as an IV infusion over 4 hours via a peripheral or central line using an infusion set with an in-line sterile, nonpyrogenic, low protein-binding, 0.2-micrometer polyethersulfone filter. Do not infuse zenocutuzumab concomitantly in the same IV line with other medications. Administer in a facility with adequate personnel and appropriate emergency resuscitation equipment to manage infusion-related reactions (IRR). Prior to the first infusion, premedicate with an antipyretic, an H1 antihistamine, and a corticosteroid. Prior to subsequent infusions, premedicate with an antipyretic and an H1 antihistamine to reduce the risk of IRR; corticosteroid premedication is optional after the initial infusion.
If refrigerated, allow diluted solution to reach room temperature (~30 minutes) prior to administration. Diluted zenocutuzumab solution must be administered within 6 hours from the end of preparation if stored at room temperature (15°C to 25°C [59°F to 77°F]) or 28 hours from the end of preparation if stored under refrigeration (2°C to 8°C [36°F to 46°F]). If the infusion time exceeds the recommended storage time, discard the infusion bag and prepare a new infusion bag to continue the infusion.
Monitor closely during infusion and for at least 1 hour following the completion of the first zenocutuzumab infusion and as clinically indicated for signs and symptoms of IRR. Interrupt infusion if an IRR occurs; depending on the severity, may restart (with the infusion rate reduced) or discontinue infusion (if grade 4).
Infusion set should be made of PVC, polyethylene, polyurethane, or polybutadiene.
Non–small cell lung cancer, advanced, unresectable or metastatic, NRG1 fusion positive: Treatment of advanced, unresectable or metastatic non–small cell lung cancer harboring a neuregulin 1 (NRG1) gene fusion in adults with disease progression on or after prior systemic therapy.
Pancreatic adenocarcinoma, advanced, unresectable or metastatic, NRG1 fusion positive: Treatment of advanced, unresectable or metastatic pancreatic adenocarcinoma harboring a NRG1 gene fusion in adults with disease progression on or after prior systemic therapy.
Zenocutuzumab may be confused with zanidatamab, zanubrutinib, zolbetuximab.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 2 months after the last dose of zenocutuzumab.
Zenocutuzumab is a bispecific humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Ref).
Based on the mechanism of action, in utero exposure to zenocutuzumab may cause fetal harm. Oligohydramnios, manifesting in fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported in patients receiving similar agents during pregnancy.
Monitor for oligohydramnios in patients exposed to zenocutuzumab during pregnancy or within 2 months prior to conception. Perform appropriate fetal testing appropriate for GA.
It is not known if zenocutuzumab is present in breast milk.
Zenocutuzumab is a bispecific humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Ref).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Also consider the elimination half-life and washout period of 2 months.
Assessment for NRG1 gene fusion in tumor specimens. Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Assess left ventricular ejection fraction at baseline and monitor at regular intervals during treatment as clinically indicated.
Monitor closely during infusion and for at least 1 hour following the completion of the first zenocutuzumab infusion and as clinically indicated for signs and symptoms of infusion-related reactions (IRR); monitor for signs and symptoms of hypersensitivity or anaphylactic reactions. Monitor for new or worsening pulmonary symptoms indicative of interstitial lung disease (ILD)/pneumonitis (eg, dyspnea, cough, fever).
Additional cardiovascular monitoring (guideline recommendations): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (Ref). Obtain a baseline echocardiography (transthoracic preferred) and repeat every 3 months during treatment (may reduce to every 4 to 6 months if normal and asymptomatic), assess more frequently if clinically indicated and obtain echocardiography within 12 months after completion; in high- and very high-risk patients, assess troponin and natriuretic peptide at baseline and consider assessing every 2 to 3 cycles, and at 3 and 12 months after completion of therapy; in low- and moderate-risk patients, consider troponin and natriuretic peptide at baseline, every 3 months and 12 months after completion of therapy (Ref).
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Zenocutuzumab is a potent immunoglobulin G1 (IgG1) bispecific HER2- and HER3-directed antibody. It binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization, preventing NRG1 binding to HER3, and downstream HER2/HER3 signaling (Ref). Inhibition of HER2/HER3 decreased cell proliferation and signaling through the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. Zenocutuzumab additionally mediates antibody-dependent cellular cytotoxicity (ADCC) through modification of the IgG1 subunit to enhance Fc receptor affinity (Ref). Zenocutuzumab demonstrated antitumor activity in NRG1 fusion-positive lung and pancreatic cancer animal models.
Distribution: Vd: 6 L.
Metabolism: Zenocutuzumab is expected to be metabolized into small peptides via catabolic pathways.
Half-life elimination: Steady state: 8 days.
Excretion: Clearance: 0.022 L/hour.
