SEM-ip-LI-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, programmed death-1 inhibitors

• Metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation.
• Locally advanced basal cell carcinoma (BCC) in patients previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.
• Metastatic BCC in patients previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.
• First-line treatment of non-small cell lung cancer (NSCLC) in patients whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) 50%] (but no EGFR, ALK or ROS1 aberrations), and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or is metastatic.

• Programmed death receptor-1 (PD-1) blocking antibody (an IgG4 kappa immunoglobulin) that binds to PD-1 and blocks its interaction with its ligands, PD-L1 and PD-L2, resulting in activation of the immune system and decreased tumor growth.

• Decreased progression of metastatic or locally advanced CSCC or BCC.
• Improved survival in NSCLC.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-life: 19 days.

(response)

ROUTE	ONSET	PEAK	DURATION
IV	within 6 mo	unknown	may persist for 8 mo

Contraindicated in:

• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Allogeneic hematopoietic stem cell transplantation recipients (↑ risk of transplant-related complications)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: MYOCARDITIS, pericarditis, vasculitis.

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), pruritus, rash.

EENT: iritis, uveitis.

Endo: ADRENAL INSUFFICIENCY, hypothyroidism, hyperthyroidism, hypoparathyroidism, hypophysitis, type 1 diabetes.

F and E: hyponatremia, hypophosphatemia.

GI: COLITIS, HEPATITIS, constipation, ↓appetite, diarrhea, nausea, gastritis, pancreatitis.

GU: nephritis.

Hemat: anemia, hemolytic anemia, lymphopenia.

MS: RHABDOMYOLYSIS, pain, myositis.

Neuro: autoimmune neuropathy, Guillain-Barré syndrome, myasthenic syndrome, myelitis , ENCEPHALITIS, MENINGITIS, fatigue.

Resp: PNEUMONITIS.

Misc: INFUSION-RELATED REACTIONS.

Drug-Drug:

• None reported.

• IV (Adults): 350 mg every 3 wk until disease progression or unacceptable toxicity.

• Solution for injection: 50 mg/mL;

• Monitor for signs and symptoms of immune-mediated pneumonitis (new or worsening cough, chest pain, shortness of breath) periodically during therapy. For Grade 2 reactions, hold cemiplimab. For Grade 3 or 4 reactions, permanently discontinue cemiplimab. Systemic corticosteroids have been used for treatment.
• Monitor for signs and symptoms of immune mediated colitis (diarrhea, blood or mucus in stools, severe abdominal pain) periodically during therapy. For Grade 2 or 3 colitis, hold cemiplimab. For Grade 4, discontinue cemiplimab permanently. Treat with systemic corticosteroids.
• Monitor for immune-mediated endocrinopathies (adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, Type 1 diabetes mellitus). May cause primary or secondary adrenal insufficiency. For Grade 2 adrenal insufficiency, start symptomatic treatment, including hormone replacement, as indicated. If symptoms of immune-mediated hypophysitis (headache, photophobia, visual field defects) occur, begin hormone replacement therapy. If symptoms of immune-mediated thyroiditis (hyperthyroidism, may be followed by hypothyroidism) occur, begin hormone replacement or medical management of hyperthyroidism as indicated. If symptoms of hyperglycemia or other signs and symptoms of diabetes occur, begin insulin therapy as indicated.If endocrinopathies of Grades 3 or 4 occur, permanently discontinue cemiplimab.
• Monitor for signs and symptoms of immune-mediated skin reactions (rash, pruritus, blistering, painful sores in mouth, nose, throat, genital area) periodically during therapy. Topical emollients and/or topical corticosteroids may treat mild to moderate non-exfoliative rashes. May cause exfoliative dermatitis (SJS, TEN, DRESS). If SJS, TEN, or DRESS is suspected, hold cemiplimab. If SJS, TEN, or DRESS are confirmed, permanently discontinue cemiplimab.
• Monitor for signs and symptoms of myocarditis (chest pain, irregular heartbeat, shortness of breath, swelling of ankles) during therapy. If Grade 2, 3, or 4 myocarditis occur, discontinue cemiplimab permanently.
• Monitor for signs and symptoms of neurological toxicities (confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs) during therapy. If Grade 2 neurological toxicities occur, hold cemiplimab. If Grades 3 or 4 occur, permanently discontinue cemiplimab.
• Monitor for signs and symptoms of infusion-related reactions (chills or shaking, itching or rash, flushing, shortness of breath, wheezing, dizziness, fever, feeling faint, back or neck pain, facial swelling) during therapy. If Grade 1 or 2 reactions occur, Interrupt of slow rate of infusion. If Grade 3 or 4 reactions occur, Permanently discontinue cemiplimab.

• Verify negative pregnancy test before starting therapy.
  • Patient selection with locally advanced or metastatic NSCLC is based on PD-L1 expression on tumor cells. Information on FDA-approved tests for the detection of PD-L1 expression is available at: http://www.fda.gov/CompanionDiagnostics.
  • Monitor liver and thyroid function tests at baseline and periodically during therapy. If AST or ALT ↑ to 3 and 8 times the upper limit of normal (ULN) or if total bilirubin ↑ to 3 times ULN, hold cemiplimab. If AST or ALT ↑ to >10 times ULN or total bilirubin ↑ to >1.5 and 3 times the ULN, permanently discontinue cemiplimab. Administer systemic corticosteroids to treat. For patients with hepatitis with tumor involvement of the liver, if baseline AST or ALT >1 and 3 times ULN and increases to >5 and 10 times ULN or baseline AST or ALT >3 and 5 times ULN and increases to >8 and 10 times ULN, hold cemiplimab. If AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN, permanently discontinue cemiplimab.
  • Monitor for signs and symptoms of nephritis. If Grade 2 or 3 increased serum creatinine occurs, hold cemiplimab. If Grade 4 increased serum creatinine occurs, permanently discontinue cemiplimab.
  • May cause increased INR, lymphopenia, anemia, hyponatremia, hypophosphatemia, and hypercalcemia.

• Intermittent Infusion: Allow solution to come to room temperature before infusing.
  Diluent: Withdraw 7 mL from cemiplimab vial and dilute with 0.9% NaCl or D5W. Mix by inverting gently; do not shake. Concentration: 1 mg/mL to 20 mg/mL.Solution is clear to slightly opalescent, colorless to pale yellow; may contain trace amounts of translucent to white particles. Do not administer solutions that are cloudy, discolored, or contain other particulate matter. Stable at room temperature for up to 8 hr or 24 hr if refrigerated.
• Rate: Infuse over 30 min through a sterile in-line or add-on 0.2- to 5-micron filter.

• Explain purpose of cemiplimab to patient and family and inform of potential adverse reactions.
• Advise patient to notify heath care professional immediately if signs and symptoms of pneumonitis, liver problems (yellowing of skin or whites of eyes, severe nausea or vomiting, pain on right side of abdomen, drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, feeling less hungry than usual), skin rash, or infusion-related reactions occur.
• Advise patient to notify health care professional if signs and symptoms of hormone gland problems (persistent or unusual headaches, rapid heart beat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deepening voice, very low blood pressure, frequent urinating, nausea or vomiting, abdominal pain, changes in mood or behavior [decreased sex drive, irritability, forgetfulness], kidney problems (decrease in amount of urine, blood in urine, ankle swelling, loss of appetite) or problems in other organs (headache, tiredness or weakness, sleepiness, changes in heartbeat [beating fast, seeming to skip a beat, pounding sensation], hallucinations, severe or persistent muscle pain, severe muscle weakness, bruises or bleeding, changes in eyesight, confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures, swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
• Rep: May be teratogenic. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 4 mo after last dose. Advise patient to notify health care professional promptly if pregnancy is suspected.

• Decreased progression of metastatic or locally advanced CSCC or BCC.
• Improved survival in NSCLC.

Libtayo

• Risk for infection (Adverse Reactions).