ZENOCUTUZUMAB-ZBCO INJ,SOLN

Clinical Criteria Summary

Interstitial Lung Disease or pneumonitis
Clinically significant cardiac disease defined as: Baseline Left Ventricular Ejection Fraction < 50%, Uncontrolled hypertension or arrhythmia, Congestive Heart Failure (New York Heart Association Class 3 or 4)
Platelets <75 X 109/L or Hemoglobin <9 grams/dL
Absolute Neutrophil Count <1.5 x 109/L unless Duffy-null phenotype
Total bilirubin > 1.5 X Upper Limit of Normal unless due to Gilbert’s syndrome
Creatine Clearance < 30ml/min
Pregnancy
Lactation

Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Goals of care and role of Palliative Care consult have been discussed and documented

NRG1 gene fusion positive (RNA based sequencing preferred) Non-Small Cell Lung Cancer with progression on or after prior systemic therapy including platinum-based chemotherapy and/or targeted therapy if clinically indicated
NRG1 gene fusion positive (RNA based sequencing preferred) advanced, unresectable, or metastatic pancreatic adenocarcinoma with progression on or after prior systemic therapy including fluoropyrimidine- and/or gemcitine-based chemotherapy

For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 months after stopping treatment

Adults with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion
Adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring a NRG1 gene fusion
Disease progression on or after prior systemic therapy

750 mg IV every 2 weeks until disease progression or unacceptable toxicity
First dose requires premedication with a corticosteroid such as dexamethasone 10 mg, an H1 antihistamine equivalent to dexchlorpheniramine 5 mg, and acetaminophen 1000 mg
Corticosteroid may not be indication in subsequent cycles; may be used as necessary for future doses

Monitor for at least 1 hour following first infusion due to risk of infusion-related reactions/hypersensitivity/anaphylaxis
Evaluate baseline LVEF and monitor at regular intervals during treatment as clinically indicated
Assess for interstitial lung disease/pneumonitis
Contraindications: None

Both FDA approvals are under accelerated approval based on overall response rate (ORR)
Not yet placed on VA clinical pathways for NSCLC or pancreatic adenocarcinoma
Second or third-line treatment option for NRG1 gene fusion positive NSCLC who have progressed on/after systemic therapy platinum-based chemotherapy and/or targeted therapy if clinically indicated
Second- or third-line treatment option for NRG1 gene fusion positive pancreatic adenocarcinoma with progression on/after systemic therapy including fluoropyrimidine- and/or gemcitabine-based chemotherapy