cemiplimab (Rx)

>10% (CSCC)

All grades

• Fatigue (34%)
• Rash (31%)
• Diarrhea (25%)
• Musculoskeletal pain (24%)
• Nausea (21%)
• Pruritus (18%)
• Cough (14%)
• Constipation (13%)
• Anemia (11%)
• Arthralgia (11%)
• >10% (BCC) H3
• All grades H4
• Fatigue (49%)
• Musculoskeletal pain (33%)
• Diarrhea (25%)
• Rash (22%)
• Pruritus (20%)
• Upper respiratory tract infection (15%)
• Decreased appetite (14%)
• Anemia (13%)
• Nausea (12%)
• Urinary tract infection (12%)
• Headache (12%)
• Constipation (11%)
• Dyspnea (11%)
• Hypertension (11%)

Grade 3 or 4

• Hyponatremia (3.1%)
• Activated partial thromboplastin time prolonged (2.3%)
• Lymphocyte count decreased (2.3%)
• Hypokalemia (1.5%)

1-10% (CSCC)

All grades

• Hypothyroidism (10%)
• Decreased appetite (10%)
• Vomiting (10%)
• Pneumonitis (≥2%)
• Cellulitis (≥2%)
• Sepsis (≥2%)
• Pneumonia (≥2%)

Grade 3 or 4

• Lymphopenia (9%)
• Anemia (5%)
• Hyponatremia (5%)
• Hypophosphatemia (4%)
• Anemia (4%)
• Musculoskeletal pain (3%)
• Fatigue (3%)
• Hypercalcemia (2%)
• Increased AST (2%)
• Increased INR (2%)
• Rash (1%)
• Arthralgia (1%)

1-10% (BCC)

All grades

• Urinary tract infection (≥1.5%)
• Colitis (≥1.5%)
• Acute kidney injury (≥1.5%)
• Adrenal insufficiency (≥1.5%)
• Anemia (≥1.5%)
• Infected neoplasm (≥1.5%)
• Somnolence (≥1.5%)

Grade 3 or 4

• Hypertension (4.5%)
• Fatigue (3.8%)
• Urinary tract infection (2.3%)
• Musculoskeletal pain (1.5%)
• Decreased appetite (1.5%)
• Headache (1.5%)
• Acute kidney injury (1.5%)
• Cachexia (1.5%)

<1% (Grade 3 or 4)

CSCC

• Vomiting (0.5%)
• Constipation (0.5%)
• Diarrhea (0.5%)

BCC

• Nausea (0.8%)
• Constipation (0.8%)
• Rash (0.8%)
• Anemia (0.8%)

Contraindications

None

Cautions

Based on cemiplimab’s mechanism of action, can cause fetal harm when administered to pregnant women

Severe or life-threatening infusion-related reactions reported; monitor patients for signs and symptoms of infusion-related reactions; common symptoms of infusion-related reaction include nausea, pyrexia, and vomiting; interrupt or slow rate of infusion or permanently discontinue therapy based on severity of reaction

Severe and fatal immune-mediated adverse effects

• The monoclonal antibody binds to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1pathway, thereby removing inhibition of immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions
• Incidence and severity of immune-mediated adverse reactions reported to be similar when administered as a single agent or in combination with chemotherapy
• Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue; immune-mediated adverse reactions can occur at any time after starting PD-1/PD-L1 blocking antibody
• While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies
• Immune-mediated adverse reactions affecting more than one body system can occur simultaneously
• Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies; monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions
• Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment; in cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection; institute medical management promptly, including specialty consultation as appropriate
• Withhold or permanently discontinue therapy depending on severity; in general, if therapy requires interruption or discontinuation, administer systemic corticosteroid therapy (1-2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less
• Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month; consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids
• Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, hypophysitis, hypothyroidism or hyperthyroidism, thyroiditis, type 1 diabetes mellitus, nephritis, and dermatologic reactions reported
• Other immune-mediated adverse reactions involving other systems (eg, neurological, cardiovascular, ocular) were also reported in <1% of patients or were reported with other PD-1/PD-L1 blockers
• Usually manifest during treatment and after discontinuation treatment; immune-mediated adverse reactions affecting more than one body system can occur simultaneously
• Immune-mediated dermatologic reactions, including erythema multiforme and pemphigoid, SJS and TEN reported; all dermatologic reactions were treated with systemic corticosteriods in clinical trial; ~22% recurrence of reactions after re-initiation of therapy
• Evaluate clinical chemistries, including liver tests and thyroid function tests, at baseline and periodically during treatment; institute medical management promptly to include specialty consultation as appropriate

Complications of allogeneic hematopoietic stem cell transplantation (HSCT)

• Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 inhibitor
• Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
• These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
• Closely monitor for evidence of transplant-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1 inhibitor before or after an allogeneic HSCT

Pregnancy

May cause fetal harm when administered to pregnant females

Verify pregnancy status in females of reproductive potential before initiation

Advise women of the potential risk to a fetus

Animal data

• Studies in mice demonstrated PD-1/PD-L1 can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death

Contraception

• Females of reproductive potential: Use effective contraception during treatment and for at least 4 months after last dose

Lactation

There are no data regarding distribution into human milk, or the drug’s effect on breastfed children or on milk production

Advise women not to breastfeed during treatment and for at least 4 months after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monoclonal antibody that targets checkpoint inhibitor PD-1 (programmed death 1) and blocks its interaction with PD-L1 and PD-L2, releasing the PD-1 pathway-mediated inhibition of the immune response, including antitumor immune response, thereby decreasing tumor growth

Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production

Absorption

Peak plasma concentration (steady-state): 171 mcg/mL

Minimum concentration (steady-state): 61 mcg/mL

Steady-state reached: ~4 months

Distribution

Vd: 5.3 L

Elimination

Half-life: 20.3 days (steady-state)

Clearance: 0.29 L/day (after first dose); 0.2 L/day (steady-state)

IV Compatibilities

0.9% NaCl

D5W

IV Preparation

Visually inspect for particulate matter and discoloration; solution should appear clear to slightly opalescent, colorless to pale yellow and may contain trace amounts of translucent-to-white particles

Discard if solution is cloudy, discolored, or contains extraneous particulate matter other than trace amounts of translucent-to-white particles

Do not shake

Withdraw 350 mg (7 mL) from vial and dilute with 0.9% NaCl or D5W to a final concentration between 1-20 mg/mL

Mix diluted solution by gentle inversion; do not shake

Discard unused drug or waste material

IV Administration

Infuse over 30 minutes through an IV line containing a sterile, in-line or add-on 0.2 to 5-micron filter

Storage

Unopened vials

• Refrigerate at 2-8°C (36-46°F) in original carton
• Protect from light
• Do not freeze or shake

Diluted solution

• Store at room temperature up to 25°C (77°F) for no more than 8 hr from time of preparation to end of infusion, OR
• Refrigerate at 2-8°C (36-46°F) for no more than 24 hr from time of preparation to end of infusion
• Allow diluted solution to come to room temperature before administration
• Do not freeze