General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
sem-ip-li-mab

Trade Name(s)

• Libtayo

Ther. Class.

antineoplastics

Pharm. Class.

monoclonal antibodies

programmed death-1 inhibitors

Indications

• Metastatic or locally advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or curative radiation.
• Locally advanced or metastatic basal cell carcinoma 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 ≥ 50%] (but no epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], or ROS1 aberrations), and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or is metastatic.
• First‐line treatment of NSCLC with no EGFR, ALK, or ROS1 aberrations and that is either locally advanced where patients are not candidates for surgical resection/definitive chemoradiation or metastatic (in combination with platinum-based chemotherapy).

Action

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.

Therapeutic Effect(s):

• Decreased progression of metastatic or locally advanced cutaneous squamous cell carcinoma or basal cell carcinoma.
• Improved survival in NSCLC.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: 19 days

TIME/ACTION PROFILE (response)

Contraindication/Precautions

Contraindicated in:

• OB:  Pregnancy;
• 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.

Adverse Reactions/Side Effects

CV: IMMUNE-MEDIATED MYOCARDITIS, immune-mediated pericarditis, immune-mediated vasculitis

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

EENT: immune-mediated iritis, immune-mediated uveitis

Endo: immune-mediated hypothyroidism, hypoparathyroidism, IMMUNE-MEDIATED ADRENAL INSUFFICIENCY, immune-mediated hyperthyroidism, immune-mediated hypophysitis, immune-mediated type 1 diabetes

F and E: hyponatremia, hypophosphatemia

GI: constipation, diarrhea, nausea, IMMUNE-MEDIATED COLITIS, immune-mediated gastritis, IMMUNE-MEDIATED HEPATITIS, immune-mediated pancreatitis

GU: immune-mediated nephritis

Hemat: anemia, immune-mediated hemolytic anemia, lymphopenia

Metabolic: ↓ appetite

MS: pain, immune-mediated myositis, IMMUNE-MEDIATED RHABDOMYOLYSIS

Neuro: autoimmune neuropathy, IMMUNE-MEDIATED ENCEPHALITIS, immune-mediated Guillain-Barré syndrome, IMMUNE-MEDIATED MENINGITIS, immune-mediated myasthenic syndrome, immune-mediated myelitis, fatigue

Resp: IMMUNE-MEDIATED PNEUMONITIS

Misc: INFUSION-RELATED REACTIONS

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

Locally Advanced/Metastatic Squamous Cell Carcinoma or Locally Advanced/Metastatic Basal Cell Carcinoma

IV (Adults): 350 mg every 3 wk; continue until disease progression, unacceptable toxicity, or up to 24 mo.

Non-Small Cell Lung Cancer

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

Availability

Solution for injection: 50 mg/mL

Assessment

• Monitor for signs/symptoms of immune-mediated pneumonitis (new or worsening cough, chest pain, shortness of breath) periodically during therapy.  If Grade 2 reactions occur,  hold cemiplimab.  If Grade 3 or 4 reactions occur,  permanently discontinue cemiplimab. Systemic corticosteroids have been used for treatment.
• Monitor for signs/symptoms of immune mediated colitis (diarrhea, blood or mucus in stools, severe abdominal pain) periodically during therapy.  If Grade 2 or 3 colitis occurs,  hold cemiplimab.  If Grade 4 colitis occurs,  permanently discontinue cemiplimab. 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.  If Grade ≥2 adrenal insufficiency occurs,  start symptomatic treatment, including hormone replacement, as indicated.  If signs/symptoms of immune-mediated hypophysitis (headache, photophobia, visual field defects) occur, begin hormone replacement therapy.  If signs/symptoms of immune-mediated thyroiditis (hyperthyroidism, may be followed by hypothyroidism) occur,  begin hormone replacement or medical management of hyperthyroidism as indicated.  If signs/symptoms of hyperglycemia or other signs/symptoms of diabetes occur,  begin insulin therapy as indicated. If endocrinopathies of Grades 3 or 4 occur,  permanently discontinue cemiplimab.
• Monitor for signs/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 nonexfoliative 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/symptoms of myocarditis (chest pain, irregular heartbeat, shortness of breath, swelling of ankles) during therapy.  If Grade 2, 3, or 4 myocarditis occur,  permanently discontinue cemiplimab.
• Monitor for signs/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 neurological toxicities occur,  permanently discontinue cemiplimab.
• Monitor for signs/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 or slow rate of infusion.  If Grade 3 or 4 reactions occur,  permanently discontinue cemiplimab.

Lab Test Considerations:

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 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 ↑ to >5 and ≤10 times ULN or baseline AST or ALT >3 and ≤5 times ULN and ↑ to >8 and ≤10 times ULN,  hold cemiplimab.  If AST or ALT ↑ to >10 times ULN or total bilirubin ↑ to >3 times ULN,  permanently discontinue cemiplimab.
• Monitor for signs/symptoms of nephritis.  If Grade 2 or 3 ↑ serum creatinine occurs,  hold cemiplimab.  If Grade 4 ↑ serum creatinine occurs,  permanently discontinue cemiplimab.
• May cause ↑ INR, lymphopenia, anemia, hyponatremia, hypophosphatemia, and hypercalcemia.

Implementation

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy.
• Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
• Advise patient to notify heath care provider immediately if signs/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 provider if signs/symptoms of hormone gland problems (persistent or unusual headaches, rapid HR, ↑ 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 BP, frequent urinating, nausea or vomiting, abdominal pain, changes in mood or behavior [↓ sex drive, irritability, forgetfulness]), kidney problems (↓ in amount of urine, blood in urine, ankle swelling, loss of appetite), or problems in other organs (headache, tiredness or weakness, sleepiness, changes in HR [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).
• Rep:  May cause fetal harm. Advise women of reproductive potential to use effective contraception and avoid breastfeeding during and for >4 mo after last dose. Advise patient to notify health care provider promptly if pregnancy is planned or suspected.

Evaluation/Desired Outcomes

• Decreased progression of metastatic or locally advanced cutaneous squamous cell carcinoma or basal cell carcinoma.
• Improved survival in NSCLC.