Usual Adult Dose for Endometrial Carcinoma

Initial dose:

• Dose 1 through Dose 4: 500 mg IV over 30 minutes every 3 weeks

Maintenance dose:

• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1000 mg IV over 30 minutes every 6 weeks

Duration of therapy:

• Until disease progression or unacceptable toxicity

Use: For the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), as determined by an approved test, that has progressed on or following prior treatment with a platinum-containing regimen.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

No dose reductions of this drug are recommended. In general, withhold therapy for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue therapy for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less prednisone equivalent per day within 12 weeks of initiating steroids.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
PNEUMONITIS:

• Grade 2: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 3 or 4 or recurrent Grade 2: Permanently discontinue therapy.

COLITIS:

• Grade 2 or 3: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 4: Permanently discontinue therapy.

HEPATITIS WITH NO TUMOR INVOLVEMENT OF THE LIVER:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) increases to more than 3 and up to 8 times upper limit of normal (ULN) or total bilirubin (TB) increases to more than 1.5 and up to 3 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids

AST or ALT increases to more than 8 x ULN or TB increases to more than 3 x ULN: Permanently discontinue therapy.
HEPATITIS WITH TUMOR INVOLVEMENT OF THE LIVER (if AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue this drug based on recommendations for hepatitis with no liver involvement):

• Baseline AST or ALT is more than 1 and up to 3 x ULN and increases to more than 5 and up to 10 x ULN or baseline AST or ALT is more than 3 and up to 5 x ULN and increases to more than 8 and up to 10 x ULN OR baseline AST or ALT is more than 3 and up to 5 x ULN and increases to more than 8 and up to 10 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• AST or ALT increases to more than 10 x ULN or TB increases to more than 3 x ULN: Permanently discontinue therapy.

ENDOCRINOPATHIES:

• Grade 2, 3, or 4: Withhold therapy if not clinically stable; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids

NEPHRITIS WITH RENAL DYSFUNCTION:

• Grade 2 or 3 increased creatinine: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 4 increased creatinine: Permanently discontinue therapy.

EXFOLIATIVE DERMATOLOGIC CONDITIONS:

• Suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS): Withhold therapy if not clinically stable; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Confirmed SJS, TEN, or DRESS: Permanently discontinue therapy.

MYOCARDITIS:

• Grade 2, 3, or 4: Permanently discontinue therapy.

NEUROLOGICAL TOXICITIES:

• Grade 2: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue therapy if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 3 or 4: Permanently discontinue therapy.

INFUSION-RELATED REACTIONS:

• Grade 1 or 2: Interrupt or slow the rate of infusion.
• Grade 3 or 4: Permanently discontinue therapy.

Precautions

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

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 infusion solution IV over 30 minutes through an IV line using tubing made of polyvinyl chloride or platinum cured silicon; fittings made of polyvinyl chloride or polycarbonate; and a sterile, non-pyrogenic, low-protein binding, 0.2-micron, in-line, or add-on filter.
• Do not administer this drug as an IV push or bolus injection.
• Do not co-administer other drugs through the same infusion line.

Storage requirements:

• Store in original carton until time of preparation to protect from light.
• The prepared dose may be stored at room temperature for no more than 6 hours from the time of preparation until the end of infusion or refrigerated at 2C to 8C (36F to 46F) for no more than 24 hours from time of preparation until end of infusion.
• If refrigerated, allow the diluted solution to come to room temperature prior to administration.
• Discard after 6 hours at room temperature or after 24 hours under refrigeration.
• Do not freeze.

Reconstitution/preparation techniques:

• Visually inspect the solution for particulate matter and discoloration.
• The solution should be clear to slightly opalescent, colorless to yellow.
• Discard the vial if visible particles are observed.
• Do not shake.
• Mix diluted solution by gentle inversion.
• Do not shake.
• Discard any unused portion left in the vial.
• The manufacturer product information should be consulted.

IV compatibility:

• This drug is compatible with 0.9% Sodium Chloride Injection or 5% Dextrose Injection.

Monitoring:

• All patients should be monitored for symptoms and signs of immune-related adverse reactions.
• Clinical chemistries, including liver and renal tests and thyroid function tests, should be evaluated at baseline and periodically during treatment.

Patient advice:

• Read the Patient Information and Instructions for Use.