Tarlatamab Dosage

Usual Adult Dose for Small Cell Lung Cancer

Step-up Dosing Schedule to be administered as an intravenous infusion over one hour:
Cycle 1:

• Day 1: Step-up dose 1 mg IV
• Day 8: 10 mg IV
• Day 15: 10 mg IV

Cycle 2:

• Day 1 and 15: 10 mg IV

Cycles 3 and 4

• Day 1 and 15: 10 mg IV

Cycle 5 and subsequent infusions: 10 mg IV

Duration of therapy: After step-up dosing schedule, administration is every 2 weeks until disease progression or unacceptable toxicity.

Comments:

• Should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions

Use: Adult patients with extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy

Renal Dose Adjustments

Mild and Moderate Renal Dysfunction: No adjustment recommended.
Severe Renal Dysfunction: Data not available

Liver Dose Adjustments

Mild and Moderate Liver Dysfunction: No adjustment recommended.
Severe Liver Dysfunction: Data not available

Hepatotoxicity Dose Adjustment:

• Grade 3 Increased ALT or AST or bilirubin: Withhold until improvement to Grade 1 or less.
• Grade 4 Increased ALT or AST or bilirubin: Permanently discontinue treatment.
• AST or ALT greater than 3 x upper limit of normal (ULN) with total bilirubin greater than 2 x ULN in the absence of alternative causes: Permanently discontinue treatment.

Dose Adjustments

RESTARTING AFTER DOSAGE DELAY

• Last dose: 1 mg on Cycle 1, Day 1:
• Delay: 14 days or less: Administer 10 mg, and then resume with dosage schedule.
• More than 14 days: Administer step-up dose 1 mg. If tolerated, increase to 10 mg one week later, then resume planned dosage schedule.

• Last dose: 10 mg on Cycle 1, Day 8
• Delay: 21 days or less: Administer 10 mg, then resume planned dosage schedule.
• More than 21 days: Administer step-up dose 1 mg. If tolerated, increase to 10 mg one week later, then resume planned dosage schedule.

• Last Dose: 10 mg on Cycle 1, Day 15 and subsequent cycles every 2 weeks thereafter:
• Delay: 28 days or less: Administer 10 mg, then resume planned dosage schedule.
• More than 28 days: Administer step-up dose 1 mg. If tolerated, increase to 10 mg one week later, then resume planned dosage schedule.

ADVERSE REACTION MANAGEMENT

• No dose reduction is recommended. See information below for specific adverse reactions.
• CRS and ICANS Grades below are based on the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading.

CYTOKINE RELEASE SYNDROME (CRS)

• Diagnose CRS based on clinical presentation. Evaluate and treat other causes of fever, hypoxia, and hypotension.
• If CRS is suspected, manage according to the recommendations below.
• Perform lab tests to monitor hematology pulmonary, cardiac, renal, and hepatic parameters as well as disseminated intravascular coagulation (DIC).

• CRS Grade 1: Withhold treatment until event resolves, then resume at next scheduled dose. Administer symptomatic treatment for fever.
• CRS Grade 2: Withhold treatment until event resolves, then resume at next scheduled dose. Recommend hospitalization for a minimum of 24 hours with cardiac telemetry and pulse oximetry, administer symptomatic treatment for fever, supplemental oxygen and IV fluids when indicated. Consider dexamethasone 8 mg IV, consider tocilizumab or equivalent. When resuming treatment, monitor patients from the start of the infusion for 22 to 24 hours in an appropriate healthcare setting.
• CRS Grade 3: Withhold treatment until event resolves, then resume at next scheduled dose. For recurrent Grade 3 events, discontinue permanently. In addition to Grade 2 management, recommend intensive monitoring (ICU care), administer dexamethasone 8 mg IV every 8 hours up to 3 doses, administer vasopressor support and high flow oxygen as needed, recommend tocilizumab or equivalent. Prior to the next dose, administer concomitant medications recommended for Cycle 1. When resuming treatment, monitor patients from the start of the infusion for 22 to 24 hours in an appropriate healthcare setting.
• CRS Grade 4: Permanently discontinue treatment. Patient should receive ICU care, treatment per Grade 3.

NEUROLOGIC TOXICITY INCLUDING ICANS

• Grade 1: Withhold treatment until ICANS resolves, then resume at the next scheduled dose. Manage with supportive care.
• Grade 2: Withhold treatment until ICANS resolves, then resume at the next scheduled dose. Manage with supportive care, dexamethasone 10 mg IV (can repeat every 6 hours), or methylprednisolone 1 mg/kg IV every 12 hours. Monitor neurologic symptoms and consider consultation with neurologist for further evaluation and treatment. Monitor patients for 22 to 24 hours following the next dose.
• Grade 3: Withhold treatment until ICANS resolves, then resume at the next scheduled dose. If there is no improvement to Grade 1 or less within 7 days or Grade 3 toxicity reoccurs within 7 days of reinitiation, permanently discontinue. For recurrent Grade 3 events, permanently discontinue. Manage with supportive care. Recommend intensive monitoring (ICU care), consider mechanical ventilation for airway protection. Dexamethasone or equivalent 10 mg IV every 6 hours or methylprednisolone 1 mg/kg every 12 hours. Consider repeat neuroimaging (CT or MRI) every 2 to 3 days if the patient has persistent Grade 3 neurotoxicity.
• Grade 4: Permanently discontinue. Manage with ICU care, mechanical ventilation, and high dose corticosteroids. Consider repeat imaging (CT or MRI), every 2 to 3 days of persistent Garde 3 neurotoxicity. Treat convulsive status epilepticus per institutional guidelines.

Severity for the events below is based on the US National Cancer Institute Common Terminology Criteria for Adverse Events:

CYTOPENIA

• Grade 3 or Grade 4 Neutropenia: Withhold treatment until recovery to Grade 2 or less, consider administration of granulocyte colony stimulating factor (G-CSF). Permanently discontinue if recovery to Grade 2 or less does not occur within 3 weeks.
• Recurrent Grade 4 Neutropenia: Permanently discontinue.
• Febrile Neutropenia: Withhold treatment until recovery to Grade 2 or less and fever resolves.
• Hemoglobin less than 8 g/dL: Withhold treatment until Hb is 8 g/dL or greater.
• Grade 3 or Grade 4 decreased platelet count: Withhold treatment until recovery to Grade 2 or less and no evidence of bleeding.
• Recurrent Grade 4 decreased platelet count: Permanently discontinue.

INFECTIONS

• All Grades: Withhold treatment in the step-up phase until infection resolves.
• Grade 3: Withhold during the treatment phase until infection improves to Grade 1 or less.
• Grade 4: Permanently discontinue.

OTHER ADVERSE REACTIONS

• Grade 3 or Grade 4: Withhold treatment until recovery to Grade 1 or less, or baseline. Consider discontinuation if adverse reaction does not resolve within 28 days. Consider permanent discontinuation for Grade 4 events.

In all adverse event cases, concomitant medications should be administered before and after the dosage cycles, and patients should be monitored accordingly.

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

US BOXED WARNING(S):
CYTOKINE RELEASE SYNDROME (CRS) and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)

• CRS including serious or life-threatening reactions, can occur in patients receiving this drug. Initiate treatment using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold treatment until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity including ICANS, including serious or life-threatening reactions can occur. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment and treat promptly. Withhold treatment until ICANS resolves or permanently discontinue based on severity.

CONTRAINDICATIONS: None

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

To report suspected adverse reactions, contact AMGEN Inc, or the FDA at www.fda.gov/medwatch

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be administered only by a qualified healthcare professional with appropriate medical support to manage severe adverse reactions.
• Patient should be well hydrated prior to the receiving this drug.
• Administer as an IV infusion over one hour.
• Administer concomitant medications before and after the infusion to avoid the risk of CRS reactions. Read the US FDA-approved patient labeling for details and schedule of the concomitant medications.
• Follow the step-up dosing schedule to reduce the incidence and severity of CRS and other adverse events.

Storage requirements:

• Refrigerate vials and IV solution stabilizer at 2C to 8C (36F to 46F) in the original carton to protect from light until time to use, do not freeze.
• Vials may be kept at room temperature between 20C to 25C (68F to 77F) for up to 24 hours in the original carton to protect from light.

Reconstitution/preparation techniques:

• Read the US FDA-approved patient labeling for further reconstitution, dilution, and administration instructions.

Monitoring:

• Evaluate complete blood counts, liver enzymes and bilirubin prior to each dose, and as clinically indicated.
• Monitor patients for signs and symptoms of CRS, neurologic toxicity, infection, cytopenia, or hypersensitivity.
• Monitor patients from the start of the infusion to 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.

Patient advice:

• Read the Patient Information and Instructions for Use.

Further information

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

Medical Disclaimer