Zenocutuzumab Dosage

Usual Adult Dose for Non-Small Cell Lung Cancer

750 mg as an IV infusion every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Select patients for treatment based on the presence of a neuregulin 1 (NRG1) gene fusion in tumor specimens.
• These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification of clinical benefits in confirmatory trials.

Uses:

• Advanced unresectable or metastatic NRG1 fusion-positive non-small cell lung cancer with disease progression on or after prior systemic therapy
• Advanced unresectable or metastatic NRG1 fusion-positive pancreatic adenocarcinoma with disease progression on or after prior systemic therapy

Usual Adult Dose for Pancreatic Cancer

750 mg as an IV infusion every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Select patients for treatment based on the presence of a neuregulin 1 (NRG1) gene fusion in tumor specimens.
• These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification of clinical benefits in confirmatory trials.

Uses:

• Advanced unresectable or metastatic NRG1 fusion-positive non-small cell lung cancer with disease progression on or after prior systemic therapy
• Advanced unresectable or metastatic NRG1 fusion-positive pancreatic adenocarcinoma with disease progression on or after prior systemic therapy

Renal Dose Adjustments

The manufacturer product information makes no recommendation.

Liver Dose Adjustments

The manufacturer product information makes no recommendation.

Dose Adjustments

No dose reduction is recommended for this drug. Below are some dosage modifications and recommended management for adverse reactions:

INFUSION RELATED REACTIONS (IRR)/HYPERSENSITIVITY/ANAPHYLACTIC REACTIONS
Grade 3 or lower:

• Interrupt infusion if IRR is suspected and monitor patient until symptoms resolve.
• Treat symptoms as needed.
• Resume the infusion at 50% of the infusion rate at which the reaction occurred. The infusion rate may be increased if there are no additional symptoms.
• Corticosteroid premedication can be used as needed for subsequent infusions.

Grade 4 IRR or any grade hypersensitivity/anaphylactic reaction:

• Permanently discontinue treatment.

INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS
Grade 1:

• Interrupt treatment until recovery.
• Consider prompt initiation of corticosteroids once the diagnosis is suspected.
• Resume treatment after resolution.

Grade 2 or higher:

• Permanently discontinue treatment.
• Promptly treat with corticosteroids.

LEFT VENTRICULAR DYSFUNCTION:
Left ventricular ejection fraction (LVEF) is 45% to 49% and absolute decrease 10% or higher from baseline -OR- LVEF less than 45%:

• Interrupt treatment and repeat LVEF assessment within 3 weeks:
• If LVEF is less than 45% or LVEF has not recovered to within 10% from baseline, permanently discontinue treatment.
• If LVEF is 50% or greater or LVEF is 45 to 49% and recovered to within 10% of baseline, resume treatment and monitor LVEF every 12 weeks while on treatment and as clinically indicated.

Symptomatic Congestive Heart Failure (CHF):

• Permanently discontinue treatment.

OTHER CLINICALLY RELEVANT ADVERSE REACTIONS
Grade 3 or 4:

• Withhold treatment until recovery to Grade 1 or less, or baseline.
• Provide symptomatic treatment as needed.
• Resume treatment after resolution of symptoms.

Precautions

US BOXED WARNING(S):

• Embryo-fetal toxicity: Exposure to this drug during pregnancy can cause embryo-fetal harm. Advise patients of the risk and the need for effective contraception.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer premedications (below) before each infusion as recommended to reduce the risk of infusion reactions.
• Do not infuse in the same IV line with other agents.
• Infuse via a peripheral or central line.
• Administer IV infusion over 4 hours.
• If the diluted solution has been refrigerated, allow it to reach room temperature (approximately 30 minutes) before administration.

Premedications:

• Corticosteroid: Dexamethasone 10 mg, oral or IV; optional after initial infusion
• Antipyretic: Acetaminophen 1000 mg, oral or IV
• H1 Antihistamine: Dexchlorpheniramine 5 mg (or equivalent), oral or IV

Storage requirements:

• Store in a refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light.
• Do not freeze or shake.

After dilution:

• If not used immediately, store the diluted solution refrigerated at 2C to 8C (36F to 46F) and protect from light unless the infusion is initiated within 2 hours of preparation.
• During infusion:
• If the infusion time exceeds the recommended storage time, the infusion bag must be discarded and a new infusion bag prepared to continue the infusion.
• Diluted solution must by administered within 6 hours from preparation of infusion solution stored at room temperature (15C to 25C [59F to 77F]) -OR- 28 hours from end of preparation of infusion solution stored refrigerated (2C to 8C [36F to 46F]).

Reconstitution/Preparation techniques:

• Consult the manufacturer product information for further preparation and administration instructions.
• This drug must be reconstituted and further diluted before IV infusion.

IV compatibility: 0.9% Sodium Chloride Injection

General:

• To report suspected adverse reactions, contact Merus N.V. at 1-844-637-8787 (MERUSUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
• Verify the pregnancy status of females of reproductive potential prior to the initiation of treatment.

Monitoring:

• Evaluate LVEF before treatment initiation, and during treatment at regular intervals.
• Monitor for signs or symptoms of IRRs during the infusion and for at least for 1 hour following the completion of the first infusion.
• Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis such as dyspnea, cough, or fever.

Patient advice:

• Read the Patient Information and Instructions for Use.
• Seek medical attention if any symptoms of an infusion-related reaction occur.
• Seek immediate medical attention if signs/symptoms of lung disease occur (cough, fever, difficulty breathing).
• Patients of childbearing potential: Notify health care provider of a known/suspected pregnancy.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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