Usual Adult Dose for Hepatocellular Carcinoma

Tremelimumab:
Less than 30 kg: Intravenous infusion of 4 mg/kg over 60 minutes as a single dose
30 kg or more: Intravenous infusion of 300 mg over 60 minutes as a single dose

Durvalumab:
Less than 30 kg: Intravenous infusion of 20 mg/kg over 60 minutes every 4 weeks
30 kg or more: Intravenous infusion of 1500 mg over 60 minutes every 4 weeks

Comments:

• This drug is indicated in combination with durvalumab.
• Administer a single dose of this drug followed by durvalumab after 1 to 2 hours on the same day of cycle 1.
• After the first cycle of combination therapy, administer only durvalumab every 4 weeks until disease progression or unacceptable toxicity occurs.
• Refer to the durvalumab prescribing information for dosing.

Use: Treatment of adult patients with unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab.

Usual Adult Dose for Non-Small Cell Lung Cancer

Tremelimumab:
Less than 30 kg: Intravenous infusion of 1 mg/kg over 60 minutes
30 kg or more: Intravenous infusion of 75 mg over 60 minutes

• Administer on week 0, 3, 6, 9 and 16
• See prescribing information for administration schedule and complete dosing information.

Durvalumab:
Less than 30 kg: Intravenous infusion of 20 mg/kg over 60 minutes
30 kg or more: Intravenous infusion of 1500 mg over 60 minutes

• See prescribing information for dosing schedule and complete dosing information.

Duration of Therapy: Administer durvalumab until disease progression or unacceptable toxicity occurs.

Platinum-Based Chemotherapy:
Refer to prescribing information for dosing information.

Comments:

• Based on the body weight and tumor histology, calculate the appropriate dose.
• Weigh patients prior to each infusion.
• Patients who received less than 4 cycles of platinum-based chemotherapy should receive the remaining cycles (up to a total of 5) of this drug after the platinum-based chemotherapy phase in combination with durvalumab every 4 weeks.
• Start a platinum-based chemotherapy infusion 1 hour after the end of the durvalumab infusion.
• Based on physician judgement, subsequent cycles of durvalumab can be given immediately after this drug, and the duration between the end of the durvalumab infusion and the start of chemotherapy can be reduced to 30 minutes.
• Patients with non-squamous non-small cell lung cancer disease who received pemetrexed and carboplatin/cisplatin, can have optional pemetrexed therapy from week 12 until disease progression or unacceptable toxicity.

Use: For the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) in combination with durvalumab and platinum-based chemotherapy.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosage reductions are not recommended.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

• If severe (Grade 3) immune-mediated adverse reactions occur, withhold treatment.
• Permanently discontinue treatment if recurrent severe (Grade 3) immune-mediated reactions occur that require systemic immunosuppressive treatment or if severity does not reduce within 12 weeks after initiating steroids.
• If life-threatening (Grade 4) immune-mediated adverse reactions occur permanently discontinue treatment.

Refer to manufacturer product information for full details on dose modification and management of adverse reactions.

Immune-Mediated Adverse Reactions:
Pneumonitis:
Grade 2:

• Withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.

Grade 3 or 4:

• Discontinue the drug permanently.

Colitis:
Grade 2:

• Withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.

Grade 3 or 4:

• Discontinue the drug permanently.

Intestinal perforation:
All Grades:

• Discontinue the drug permanently.

Hepatitis with no tumor involvement of the liver:

• If ALT or AST increases to more than 3 and up to 8 times the ULN or total bilirubin increases to more than 1.5 and up to 3 times ULN, withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.
• If ALT or AST increases to more than 8 times ULN or total bilirubin increases to more than 3 times the ULN discontinue the drug permanently.

Hepatitis with tumor involvement of the liver:

• If AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN or AST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN, withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.
• If AST or ALT increases to more than 10 times ULN or total bilirubin increases to more than 3 times ULN discontinue the drug permanently.

Endocrinopathies:
Grade 3 or 4:

• Withhold treatment until clinically stable or permanently discontinue depending on severity.

Nephritis with Renal Dysfunction:
Grade 2 or 3 increased blood creatinine:

• Withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.

Grade 4 increased blood creatinine:

• Discontinue the drug permanently.

Exfoliative Dermatologic Conditions:
Suspected Stevens Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS):

• Withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.

Confirmed Stevens Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS):

• Discontinue the drug permanently.

Myocarditis:
Grade 2, 3, or 4:

• Discontinue the drug permanently.

Neurological Toxicities:
Grade 2:

• Withhold treatment until severity reduces to grade 1 or lower after corticosteroid tapering, or permanently discontinue the therapy if severity does not reduce within 12 weeks after initiating steroids.

Grade 3 or 4:

• Discontinue the drug permanently.

Other Adverse Reactions:
Infusion-related reactions:
Grade 1 or 2:

• Interrupt or slow the rate of infusion.

Grade 3 or 4:

• Discontinue the drug permanently.

Precautions

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 the IV infusion solution through an intravenous line containing a sterile, low-protein-binding 0.2 or 0.22-micron filter.
• After administering this drug, monitor the patient for 60 minutes before administering durvalumab.
• When administered in combination with durvalumab and pemetrexed or platinum-based chemotherapy, this drug is infused first, followed by durvalumab, and then pemetrexed or platinum-based chemotherapy on the day of dosing.
• Administer drugs using separate infusion bags and filters for each infusion.
• Do not administer other drugs simultaneously with this drug or through the same intravenous line.
• Refer to platinum-based chemotherapy and pemetrexed prescribing information for administration information.

Storage requirements:

• IV: Use immediately after reconstitution.
• IV: Refrigerate at 2C to 8C (36F to 46F); in original carton to protect from light.
• Do not freeze or shake.

Diluted drug product:

• Should not be stored for more than 28 hours refrigerated at 36F to 46F(2C to 8C).
• Should not be stored for more than 24 hours at room temperature at up to 86F (30C).

Preparation technique:

• Visually inspect the drug product for particulate matter and discoloration.
• Discard if the solution is cloudy, discolored, or visible particles are observed.
• Do not shake the vial.
• Withdraw and transfer the required volume of drug into an intravenous bag containing 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, and mix the solution by gentle inversion. Do not shake the solution.
• The maximum final concentration should not exceed 10 mg/mL.
• A maximum of 150 mL and 80 mL of diluent should be used to prepare doses of 300 mg and 4 mg/kg, respectively.
• Discard partially used and empty vials of this drug.

Patient advice:

• Read the FDA-approved patient labeling (Medication Guide).
• This drug can cause immune-mediated adverse reactions.
• Contact your healthcare provider immediately if signs or symptoms of severe adverse reactions or infusion-related reactions occur.
• This drug can cause fetal harm; exercise effective contraception during the therapy and for 3 months after the last dose.
• Breastfeeding is not recommended during use of this drug and for 3 months after the last dose.