Zenocutuzumab-zbco (Monograph)

Brand name: Bizengri
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Zenocutuzumab-zbco, a humanized immunoglobulin GA1 (IgG1) bispecific HER2- and HER3-directed antibody, is an antineoplastic agent.

Uses for Zenocutuzumab-zbco

Zenocutuzumab-zbco has the following uses:

Zenocutuzumab-zbco 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Zenocutuzumab-zbco is also 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Zenocutuzumab-zbco Dosage and Administration

General

Zenocutuzumab-zbco is available in the following dosage form(s) and strength(s):

Injection concentrate: 375 mg/18.75 mL (20 mg/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Select patients for treatment with zenocutuzumab-zbco based on the presence of an NRG1 gene fusion in tumor specimens.

• Evaluate left ventricular ejection fraction (LVEF) before initiating zenocutuzumab-zbco.

• Administer as an IV infusion, after dilution, over 4 hours.

• The recommended dosage of zenocutuzumab-zbco is 750 mg every 2 weeks until disease progression or unacceptable toxicity.

• Administer premedications before each infusion to reduce the risk of infusion-related reactions.

• See Full Prescribing Information for additional instructions on preparation and administration, and dosage modification recommendations for adverse reactions.

Cautions for Zenocutuzumab-zbco

Contraindications

None.

Warnings/Precautions

Infusion-related Reactions/Hypersensitivity/Anaphylactic Reactions

Zenocutuzumab-zbco can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity, and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all of which were Grade 1 or 2; 91% occurred during the first infusion. The median time to onset was 63 minutes (range: 13 minutes to 240 minutes) from the start of infusion.

Administer zenocutuzumab-zbco in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of the first zenocutuzumab-zbco infusion and as clinically indicated. Prior to the first zenocutuzumab-zbco infusion, premedicate with a corticosteroid, an H1 antihistamine and acetaminophen to reduce the risk of IRRs. Corticosteroid premedication can be used as necessary for subsequent infusions.

Interrupt zenocutuzumab-zbco infusion in patients with IRRs ≤ Grade 3 and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue zenocutuzumab-zbco for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

Zenocutuzumab-zbco can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with zenocutuzumab-zbco. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of zenocutuzumab-zbco occurred in 1 (0.6%) patient.

Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold zenocutuzumab-zbco in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue zenocutuzumab-zbco if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

Zenocutuzumab-zbco can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease occurred with anti-HER2 therapies, including zenocutuzumab-zbco. Treatment with zenocutuzumab-zbco has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (Grade 2 LVEF decrease [40%-50%; 10 - 19% drop from baseline]) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients including 1 (0.6%) fatal event.

Before initiating zenocutuzumab-zbco, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF less than 45% or less than 50% with absolute decrease from baseline of 10% or greater is confirmed, permanently discontinue zenocutuzumab-zbco. Permanently discontinue zenocutuzumab-zbco in patients with symptomatic congestive heart failure (CHF).

Embryo-fetal Toxicity

Based on its mechanism of action, zenocutuzumab-zbco 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 zenocutuzumab-zbco. Advise females of reproductive potential to use effective contraception during treatment with zenocutuzumab-zbco and for 2 months after the last dose.

Specific Populations

Pregnancy

Based on its mechanism of action, zenocutuzumab-zbco can cause fetal harm when administered to a pregnant woman. There are no available data on the use of zenocutuzumab-zbco in pregnant women to inform a drug-associated risk.

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, zenocutuzumab-zbco 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 zenocutuzumab-zbco is used in pregnant women, or if a patient becomes pregnant within 2 months after the last dose of zenocutuzumab-zbco.

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 zenocutuzumab-zbco 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.

Lactation

There are no data on the presence of zenocutuzumab-zbco in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG1 is known to be present in human milk. The effects of local GI exposure and limited systemic exposure in the breastfed child to zenocutuzumab-zbco are unknown. Consider the developmental and health benefits of breast feeding along with the mother's clinical need for zenocutuzumab-zbco treatment and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. This consideration should also take into account the elimination half-life of zenocutuzumab-zbco and washout period of 2 months.

Females and Males of Reproductive Potential

Zenocutuzumab-zbco can cause fetal harm when administered to a pregnant woman.

Verify the pregnancy status of females of reproductive potential prior to initiating zenocutuzumab-zbco.

Advise female patients of reproductive potential to use effective contraception during treatment with zenocutuzumab-zbco and for 2 months after the last dose.

Pediatric Use

The safety and effectiveness of zenocutuzumab-zbco have not been established in pediatric patients.

Geriatric Use

Of the 175 patients with NRG1 gene fusion positive tumors in the eNRGy study treated with zenocutuzumab-zbco at a dosage of 750 mg every 2 weeks, 75 patients (43%) were 65 years of age or older and 26 patients (15%) were 75 years of age and older. No clinically important differences in safety or efficacy were observed between patients who were ≥65 years of age and younger patients.

Common Adverse Effects

• The most common adverse reactions (≥ 10%) in patients were diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema.

• The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased GGT, decreased hemoglobin, decreased sodium, decreased platelets, increased AST, increased ALT, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased aPTT, and increased bilirubin.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Zenocutuzumab-zbco is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. Zenocutuzumab-zbco decreased cell proliferation and signaling through the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. In addition, zenocutuzumab-zbco mediates antibody-dependent cellular cytotoxicity (ADCC). Zenocutuzumab-zbco showed antitumor activity in mouse models of NRG1 fusion-positive lung and pancreatic cancers.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.

• Advise patients that zenocutuzumab-zbco can cause serious and life-threatening infusion-related reactions (IRRs). Advise patients to alert their healthcare provider immediately for any signs or symptoms of IRRs during and following the infusion.

• Inform patients that zenocutuzumab-zbco can cause serious and life threatening interstitial lung disease (ILD)/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms.

• Inform patients that zenocutuzumab-zbco can cause serious and life threatening left ventricular dysfunction. Advise patients to immediately contact their healthcare provider for new or worsening cardiovascular symptoms.

• Inform female patients of the potential risk to a fetus. Advise female patients to contact their healthcare provider with a known or suspected pregnancy.

• Advise females of reproductive potential to use effective contraception during treatment with zenocutuzumab-zbco and for 2 months after the last dose.

• Advise women not to breastfeed during treatment with zenocutuzumab-zbco and for 2 months after the last dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Zenocutuzumab Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for zenocutuzumab.

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