Cemiplimab-rwlc (Monograph)

Brand name: Libtayo
Drug class: Antineoplastic Agents
- Programmed death receptor-1 antagonist
- PD-1 Inhibitor
Chemical name: Anti-(human programmed cell death protein 1) (human monoclonal REGN2810 heavy chain), disulfide with human monoclonal REGN2810 k-chain immunoglobulin G4 dimer
Molecular formula: C₆₃₈₀H₉₈₀₈N₁₆₈₈O₂₀₀₀S₄₄
CAS number: 1801342-60-8

Medically reviewed by Drugs.com on Aug 16, 2023. Written by ASHP.

Introduction

Antineoplastic agent; fully human anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody.

Uses for Cemiplimab-rwlc

Cutaneous Squamous Cell Carcinoma

Treatment of metastatic or locally advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy.

Cemiplimab-rwlc Dosage and Administration

General

• Monitor blood chemistries and liver and thyroid function tests prior to initiation of and periodically during therapy.

Restricted Distribution

• Available through a limited network of speciality distributors or pharmacies. Consult the Libtayo website ([Web]) for specific ordering and availability information.

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Cemiplimab-rwlc injection concentrate must be diluted prior to administration.

Administer using a sterile, 0.2- to 5-μm inline or add-on filter.

Dilution

Undiluted solution should be clear to slightly opalescent and colorless to pale yellow. Do not use if cloudy or discolored or if particulate matter other than trace amounts of the translucent to white particles are present.

Withdraw 7 mL of cemiplimab-rwlc injection concentrate (containing 50 mg/mL) and dilute in a sufficient volume of 0.9% sodium chloride injection or 5% dextrose injection to a final concentration of 1–20 mg/mL. Mix diluted solution by gentle inversion; do not shake.

Discard any partially used vial.

If the diluted solution was previously refrigerated, bring to room temperature prior to administration.

Rate of Administration

Administer by IV infusion over 30 minutes.

Dosage

Adults

Cutaneous Squamous Cell Carcinoma

IV

350 mg every 3 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Therapy Interruption for Toxicity

Permanently discontinue therapy in patients experiencing persistent grade 2 or 3 immune-mediated adverse effects lasting ≥12 weeks and those requiring a corticosteroid dosage of ≥10 mg of prednisone daily (or equivalent) for ≥12 weeks. (See Warnings/Precautions under Cautions.)

Permanently discontinue therapy if grade 3 or 4 immune-mediated adverse effects recur.

Immune-mediated Pneumonitis

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until recovery to grade 0 or 1. May resume following completion of corticosteroid taper. (See Immune-mediated Pneumonitis under Cautions.)

If grade 3 or 4 immune-mediated pneumonitis occurs, permanently discontinue drug.

Immune-mediated GI Effects

If grade 2 or 3 immune-mediated colitis occurs, interrupt therapy until recovery to grade 0 or 1. May resume following completion of corticosteroid taper. (See Immune-mediated GI Effects under Cautions.)

If grade 4 immune-mediated colitis occurs, permanently discontinue drug.

Immune-mediated Hepatic Effects

For ALT or AST elevations >3 times but ≤10 times the ULN or total bilirubin concentrations exceeding but ≤3 times the ULN, interrupt therapy until recovery to grade 0 or 1. May resume following completion of corticosteroid taper. (See Immune-mediated Hepatic Effects under Cautions.)

For ALT or AST elevations >10 times the ULN or total bilirubin concentrations >3 times the ULN, permanently discontinue drug.

Immune-mediated Endocrine Effects

If grade 2–4 endocrinopathies (e.g., adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, diabetes mellitus) occur, interrupt therapy if clinically necessary. (See Immune-mediated Endocrine Effects under Cautions.)

Other Immune-mediated Adverse Effects

If any other grade 3 immune-mediated adverse effects involving a major organ occur, interrupt therapy until recovery to grade 0 or 1. May resume following completion of corticosteroid taper. (See Other Immune-mediated Effects under Cautions.)

If any other grade 4 immune-mediated adverse effects involving a major organ occur, permanently discontinue drug.

Infusion-related Reactions

If grade 1 or 2 infusion-related reactions occur, interrupt infusion or reduce infusion rate. (See Infusion-related Effects under Cautions.)

If grade 3 or 4 infusion-related reactions occur, permanently discontinue drug.

Special Populations

Hepatic Impairment

No dosage recommendations at this time. (See Special Populations under Pharmacokinetics.)

Renal Impairment

No dosage recommendations at this time. (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No special dosage recommendations at this time. (See Geriatric Use under Cautions.)

Cautions for Cemiplimab-rwlc

Contraindications

• No known contraindications.

Warnings/Precautions

Immune-mediated Pneumonitis

Immune-mediated pneumonitis, sometimes fatal, reported. Onset may occur following discontinuance of therapy.

Monitor patients for manifestations of pneumonitis.

If immune-mediated pneumonitis occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater pneumonitis occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated pneumonitis is inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Immune-mediated GI Effects

Immune-mediated colitis reported. Onset may occur following discontinuance of therapy.

Monitor patients for manifestations of colitis.

If immune-mediated colitis occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater colitis occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated colitis is inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Immune-mediated Hepatic Effects

Immune-mediated hepatitis, sometimes fatal, reported. Onset may occur following discontinuance of therapy.

Monitor patients for manifestations of hepatitis. Evaluate liver function tests prior to initiation of and periodically during therapy.

If immune-mediated hepatitis occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater ALT or AST elevations (>3 times the ULN) or total bilirubin concentrations exceeding the ULN occur, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated hepatitis is inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Immune-mediated Endocrine Effects

Immune-mediated endocrinopathies, including adrenal insufficiency, hypophysitis, thyroid dysfunction (i.e., hypothyroidism, hyperthyroidism), and diabetes mellitus (including ketoacidosis), reported. Onset may occur following discontinuance of therapy.

Monitor patients for manifestations of endocrinopathies. Evaluate thyroid function and blood glucose concentrations prior to initiation of and periodically during therapy.

If immune-mediated endocrinopathies occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) For certain grade 2 or greater endocrinopathies, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If such immune-mediated endocrinopathies are inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy. Administer hormone replacement therapy, including antidiabetic therapy (e.g., insulin), as clinically indicated.

Immune-mediated Renal Effects

Immune-mediated nephritis reported. Onset may occur following discontinuance of therapy.

Monitor patients for changes in renal function. Evaluate S_cr prior to initiation of and periodically during therapy.

If immune-mediated nephritis occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater nephritis occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated nephritis is inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Immune-mediated Dermatologic Effects

Immune-mediated rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and pemphigoid, reported. Onset may occur following discontinuance of therapy.

Monitor patients for dermatologic reactions.

If immune-mediated rash occurs, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater dermatologic reactions occur, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated dermatologic reactions are inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Other Immune-mediated Effects

Other immune-mediated adverse effects, sometimes severe or fatal, reported with anti-PD ligand 1 (anti-PD-L1) and anti-PD-1 antibodies, including cemiplimab-rwlc; ocular inflammatory toxicities (e.g., uveitis, iritis), sometimes associated with retinal detachment, visual impairment, or blindness, also reported. Onset may occur following discontinuance of therapy.

If uveitis occurs in conjunction with other immune-mediated adverse effects, consider possibility of a Vogt-Koyanagi-Harada-like syndrome; in such cases, systemic corticosteroids may be required to reduce the risk of vision loss.

If immune-mediated adverse effects occur, temporarily withhold or discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.) If grade 2 or greater adverse effects occur, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]). Once toxicity has resolved to grade 0 or 1, taper corticosteroid dosage over 1 month. If immune-mediated adverse effects are inadequately controlled by systemic corticosteroid therapy, may consider systemic immunosuppressant therapy.

Infusion-related Effects

Immune-mediated infusion-related reactions reported.

Monitor patients for manifestations of infusion-related reactions. If infusion-related reactions occur, interrupt infusion, reduce infusion rate, or permanently discontinue cemiplimab. (See Therapy Interruption for Toxicity under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. May disrupt maternal immune tolerance to the fetus and increase risk of fetal loss (abortion, stillbirth); also may increase risk of immune-mediated disorders or alter normal immune response of the developing fetus.

Avoid pregnancy during therapy. Confirm pregnancy status prior to initiating therapy. Women of childbearing potential should use an effective method of contraception while receiving cemiplimab and for ≥4 months after the last dose. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Immunogenicity

Potential for immunogenicity. Development of binding antibodies to cemiplimab reported; neutralizing antibodies not detected. Presence of anti-cemiplimab antibodies persisted in 1 of 5 patients who developed these antibodies. Data insufficient to determine clinical importance of these antibodies; however, effects on pharmacokinetics or safety (i.e., infusion-related reactions) of the drug not observed.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether cemiplimab is distributed into human milk. Discontinue nursing during therapy and for ≥4 months after the last dose.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

In clinical studies evaluating cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma, 72% of patients were ≥65 years of age and 37% were ≥75 years of age; no overall differences in safety or efficacy relative to younger adults.

Hepatic Impairment

Systemic exposure not affected by total bilirubin concentrations of 0.02–2.63 mg/dL.

Not studied in patients with moderate or severe hepatic impairment.

Renal Impairment

Systemic exposure not affected by Cl_cr ≥25 mL/minute.

Common Adverse Effects

Metastatic or locally advanced cutaneous squamous cell carcinoma: Fatigue, rash, diarrhea, nausea, musculoskeletal pain, pruritus, cough, headache, constipation, dry skin, vomiting, decreased appetite, lymphopenia, hypophosphatemia, elevated AST concentrations, hyponatremia, increased INR, anemia, hypoalbuminemia, hypercalcemia.

Drug Interactions

No formal drug interaction studies to date.

Cemiplimab-rwlc Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are linear and dose proportional over dosage range of 1–10 mg/kg IV every 2 weeks and at a dosage of 350 mg IV every 3 weeks.

Steady-state concentrations achieved by approximately 4 months.

Special Populations

Systemic exposure not affected by total bilirubin concentrations of 0.02–2.63 mg/dL or Cl_cr ≥25 mL/minute.

Age (27–96 years), gender, body weight (31–156 kg), race, cancer type, and serum albumin concentration (2.2–4.8 g/dL) do not affect systemic exposure to cemiplimab-rwlc.

Distribution

Extent

Not known whether cemiplimab is distributed into milk.

Elimination

Metabolism

Proteolytic degradation.

Half-life

19 days.

Clearance is approximately 34% lower at steady state than following initial dose.

Stability

Storage

Parenteral

Injection

2–8°C in original carton to protect from light. Do not freeze or shake.

Diluted solution may be stored at room temperature (up to 25°C) for ≤8 hours after dilution (including infusion time) or 2–8°C for ≤24 hours after dilution (including infusion time).

Compatibility

Parenteral

Solution Compatibility

Actions

• An IgG₄ immunoglobulin that is highly selective for PD-1, an immune-checkpoint receptor expressed on activated T cells, monocytes, B cells, natural kill (NK) T cells, and dendritic cells.

• Overexpression of PD-1 ligands on surface of tumor cells results in activation of PD-1 and suppression of cytotoxic T-cell activity.

• Blocks interaction between PD-1 and its ligands, resulting in enhanced tumor immune response, including enhanced antitumor immune response.

Advice to Patients

• Importance of reading the manufacturer’s medication guide.

• Risk of immune-mediated pneumonitis. Importance of informing clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.

• Risk of immune-mediated colitis. Importance of informing clinician immediately if diarrhea, severe abdominal pain, or changes in stool occur.

• Risk of immune-mediated hepatitis. Importance of informing clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, abdominal pain [particularly in the right upper quadrant], drowsiness, dark urine, easy bruising or bleeding, lack of appetite) occur.

• Risk of immune-mediated endocrinopathies. Importance of informing clinician immediately if signs and symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or diabetes mellitus occur.

• Risk of immune-mediated nephritis or renal dysfunction. Importance of informing clinician immediately if signs and symptoms of nephritis (e.g., decreased urine output, hematuria, peripheral edema, lack of appetite) occur.

• Risk of immune-mediated rash. Importance of informing clinician immediately if a new rash develops.

• Risk of infusion-related reactions. Importance of informing clinician immediately if signs and symptoms of such reactions (e.g., chills, pruritus, flushing, difficulty breathing, dizziness, fever, feeling of faintness, back or neck pain, angioedema) occur.

• Risk of fetal harm. Necessity of advising women of childbearing potential that they should use an effective method of contraception while receiving the drug and for ≥4 months after the last dose. Importance of women informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.

• Importance of advising women to avoid breast-feeding while receiving the drug and for ≥4 months after the last dose.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., autoimmune disorders, history of solid organ transplantation, hepatic or renal dysfunction, pulmonary disorders, diabetes mellitus).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What type of drug is Libtayo?

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