Zenocutuzumab

FDA Drug Information • Also known as: Bizengri

Brand Names: Bizengri
Dosage Form: LIQUID
Product Type: BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 , 8.3 )]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception [see Warnings and Precautions ( 5.4 ), Use on Specific Populations ( 8.1 , 8.3 )].

Description

11 DESCRIPTION Zenocutuzumab-zbco is a low-fucose humanized full-length immunoglobulin G1 (IgG1) bispecific HER2- and HER3-directed antibody. It has a molecular weight of approximately 146 kDa and is produced in a mammalian cell line (Chinese Hamster Ovary [CHO]) using recombinant DNA technology. BIZENGRI is a sterile, clear to slightly opalescent, colorless to slightly yellow, preservative-free injection for intravenous infusion in single-dose vials. The pH is 6.0. Each BIZENGRI vial contains 375 mg/18.75 mL zenocutuzumab-zbco at a concentration of 20 mg/mL. Each vial also contains the following inactive ingredients: histidine (34.9 mg), L-histidine hydrochloride monohydrate (51.1 mg), polysorbate 20 (3.7 mg), trehalose (1412 mg), and water for injection.

What Is Zenocutuzumab Used For?

1 INDICATIONS AND USAGE 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 ) 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 ) *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). 1.1 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Non-Small Cell Lung Cancer BIZENGRI 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 ( 14.1 )]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 1.2 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Pancreatic Adenocarcinoma BIZENGRI 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 ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion. ( 2.1 ) Evaluate left ventricular ejection fraction (LVEF) before initiating BIZENGRI. ( 2.2 ) The recommended dosage of BIZENGRI is 750 mg every 2 weeks until disease progression or unacceptable toxicity. ( 2.3 ) Administer premedications before each infusion to reduce the risk of infusion-related reactions. ( 2.4 ) Administer as an intravenous infusion, after dilution, over 4 hours. ( 2.7 ) 2.1 Patient Selection Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion in tumor specimens [see Clinical Studies ( 14.1 , 14.2 )] . An FDA-approved test for the detection of NRG1 gene fusions is not currently available. 2.2 Recommended Evaluation Before Initiating BIZENGRI Before initiating BIZENGRI, evaluate left ventricular ejection fraction (LVEF) [see Warnings and Precautions ( 5.3 )]. 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 ( 2.7 )]. Administer premedications before each BIZENGRI infusion as recommended to reduce the risk of infusion-related reactions [see Dosage and Administration ( 2.4 )] . 2.4 Recommended Premedications Prior to each infusion of BIZENGRI, administer premedications to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions ( 5.1 )] (see Table 1 ) . Table 1: Premedications Prior to BIZENGRI Infusions 1 Optional after initial BIZENGRI infusion Medication Dose Route of Administration Corticosteroid 1 Dexamethasone (10 mg) Oral or intravenous Antipyretic Acetaminophen (1,000 mg) Oral or intravenous H1 Antihistamine Dexchlorpheniramine (5 mg) or other anti-H1 equivalent Intravenous or oral 2.5 Dosage Modifications for Adverse Reactions No dose reduction is recommended for BIZENGRI. The recommended dosage modifications of BIZENGRI for adverse reactions are provided in Table 2 . Table 2: Recommended BIZENGRI Dosage Modifications and Management for Adverse Reactions Adverse Reaction Severity Dose Modifications and Management Infusion-related reactions (IRRs)/Hypersensitivity/Anaphylactic Reactions [see Warnings and Precautions ( 5.1 )] ≤ Grade 3 IRR Interrupt BIZENGRI infusion if IRR is suspected and monitor patient until reaction symptoms resolve. Provide symptomatic treatment as needed. Resume the infusion at 50% of the infusion rate at which the reaction occurred. The infusion rate may be escalated if there are no additional symptoms. Corticosteroid premedication can be used as necessary for subsequent BIZENGRI infusions [see Recommended Premedications ( 2.4 )] . Grade 4 IRR or any grade hypersensitivity/ anaphylactic reaction Permanently discontinue BIZENGRI. Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions ( 5.2 )] Grade 1 Interrupt BIZENGRI until recovery. Consider prompt...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-Related Reactions/Hypersensitivity/Anaphylaxis [ see Warnings and Precautions ( 5.1 )] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions ( 5.2 )] Left Ventricular Dysfunction [ see Warnings and Precautions ( 5.3 ) ] Embryo-Fetal Toxicity [ see Warnings and Precautions ( 5.4 ) ] 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. ( 6.1 ) 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Partner Therapeutics, Inc. at 1-888-479-5385 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 described in the WARNINGS AND PRECAUTIONS reflects exposure to BIZENGRI as a single agent at 750 mg administered intravenously every 2 weeks until disease progression or unacceptable toxicity in 175 patients with NRG1 gene fusion positive tumors in the eNRGy study. Of these, there were 99 patients with NSCLC, 39 patients with pancreatic adenocarcinoma and 37 patients with other solid tumors [see Clinical Studies ( 14.1 , 14.2 )] . Among the 175 patients who received BIZENGRI, the median duration of exposure to BIZENGRI was 5.3 months (range: 0.1 to 36), including 45% of patients exposed for at least 6 months and 15% of patients exposed for at least 1 year. In this pooled safety population, the most common (≥ 10%) adverse reactions 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. NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC eNRGy Study The safety of BIZENGRI was evaluated in the eNRGy study in 99 patients with unresectable or metastatic NSCLC with NRG1 gene fusions [see Clinical Studies ( 14.1 )]. Patients received BIZENGRI as a single agent at 750 mg intravenously every 2 weeks until disease progression or unacceptable toxicity. Among patients who received BIZENGRI, 47% were exposed for 6 months or longer and 17% were exposed for greater than one year. The median age was 66 years (range: 27 to 88), 54% were 65 years or older; 62% were female; 37% were White, 53% were Asian, 2% were Black or African American; and 1% were Hispanic or Latino. Serious adverse reactions occurred in 25% of patients who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Serious adverse reactions occurring in one patient each were: abdominal pain, acute kidney injury, ascites, bradycardia, carotid artery stenosis, cellulitis, acute cholecystitis, COVID-19, decreased appetite, dehydration, dizziness, dysphagia, hyponatremia, ileus, lymphadenitis, nausea, gastric obstruction, pericardial effusion, pneumonitis, pulmonary hypertension, sepsis, staphylococcal infection, tumor pain, urinary tract infection, viral infection and vomiting. Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of BIZENGRI 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 (see Data ) . 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 ( see Clinical Considerations ) . 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. Clinical Considerations Fetal/Neonatal Adverse Reactions 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. Data Human Data 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. Animal Data There were no animal reproductive or developmental toxicity studies conducted with zenocutuzumab-zbco. A...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied BIZENGRI (zenocutuzumab-zbco) injection is a sterile, clear to slightly opalescent, colorless to slightly yellow, preservative-free solution for intravenous infusion. Each single-dose vial contains 375 mg/18.75 mL (20 mg/mL) BIZENGRI. Two vials (equivalent to 1 dose) are packed in a single carton. (NDC 71837-1000-1 for individual vial and NDC 71837-1000-2 for a single carton). Storage and Handling Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.