Zenocutuzumab

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.

• 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 ) Adults with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 ( NRG1 ) gene fusion with disease progression on or after prior systemic therapy. ( 1.3 ) *This indication is approved under accelerated approval based on overall response rate and duration of response.ICD-10: C34.90

• None. None.contraindicated

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 , 14.3) ] . 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 ) .

Infusion-Related Reactions (IRR)/Hypersensitivity/Anaphylactic Reactions : Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor for signs and symptoms of IRR. Interrupt infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis. ( 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue BIZENGRI in patients with ≥ Grade 2 ILD/pneumonitis. ( 5.2 ) Left Ventricular Dysfunction : Assess LVEF before initiating BIZENGRI and at regular intervals during treatment as clinically indicated. Manage through treatment interruption or discontinuation. Permanently discontinue BIZENGRI in patients with symptomatic congestive heart failure (CHF). ( 5.3 ) 5.1 Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions BIZENGRI 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 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.

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.

Females and Males of Reproductive Potential : Verify pregnancy status of females prior to initiation of BIZENGRI. ( 8.3 ) 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.

Metabolism

Zenocutuzumab-zbco pharmacokinetic parameters are expressed as mean unless otherwise specified. Zenocutuzumab-zbco exposure increases proportionally over a dose range from 480 mg (0.6 times the approved recommended dosage) to 900 mg (1.2 times the approved recommended dosage).

• Dec 4, 2024BLABLA761352Merus N.v.

1. 1Drug Ineffective233%
2. 2Dysphonia233%
3. 3Diarrhoea117%
4. 4Disease Progression117%
5. 5Drug Intolerance117%
6. 6Off Label Use117%
7. 7Rash Maculo-papular117%
8. 8Thrombocytopenia117%

The 4 most recently updated of 4 ClinicalTrials.gov registrations naming Zenocutuzumab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers
  Terminated · Phase 2 · Interventional · 13 enrolled · Partner Therapeutics, Inc.
  NCT05588609updated 2026-04-27
• Early Access Program Providing HER2/HER3 Bispecific Antibody, MCLA-128, for a Patient With Advanced NRG1-Fusion Positive Solid Tumor
  Approved for marketing · Expanded access · Merus B.V.
  NCT04100694updated 2025-05-20
• A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy)
  Active not recruiting · Phase 2 · Interventional · 250 enrolled · Partner Therapeutics, Inc.
  NCT02912949updated 2025-04-29
• MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer.
  Completed · Phase 2 · Interventional · 105 enrolled · Merus B.V.
  NCT03321981updated 2024-03-07

Frequently asked questions

How does Zenocutuzumab work?

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.

What is Zenocutuzumab used for?

According to FDA labeling, Zenocutuzumab carries indications including: 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 ) Adults with advanced, unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 ( NRG1 ) gene fusion with disease progression on or after prior systemic therapy. ( 1.3 ) *This indication is approved under accelerated approval based on overall response rate and duration of response.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Zenocutuzumab?

Zenocutuzumab is classified as HER2/Neu/cerbB2 Antagonists, HER3 Antagonists, Decreased Epithelial Proliferation.

What are the brand names for Zenocutuzumab?

Zenocutuzumab is marketed under brand names including Bizengri.

What are the contraindications for Zenocutuzumab?

Zenocutuzumab labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.