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Cemiplimab: Drug information

Cemiplimab: Drug information
(For additional information see "Cemiplimab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Libtayo
Brand Names: Canada
  • Libtayo
Pharmacologic Category
  • Antineoplastic Agent, Anti-PD-1 Monoclonal Antibody;
  • Antineoplastic Agent, Immune Checkpoint Inhibitor;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult
Basal cell carcinoma, locally advanced or metastatic

Basal cell carcinoma, locally advanced or metastatic: IV: 350 mg once every 3 weeks until disease progression or unacceptable toxicity.

Cervical cancer, recurrent or metastatic

Cervical cancer, recurrent or metastatic (off-label use): IV: 350 mg once every 3 weeks for up to 96 weeks, with the option to repeat in patients who received 16 treatment cycles and experienced disease progression in the posttreatment follow-up phase; may continue beyond progression if a response consistent with pseudo-progression occurs and in the absence of rapid progression, worsening performance status, or unacceptable toxicity (Tewari 2022).

Cutaneous squamous cell carcinoma, metastatic or locally advanced

Cutaneous squamous cell carcinoma, metastatic or locally advanced: IV: 350 mg once every 3 weeks until disease progression or unacceptable toxicity (Migden 2018; Migden 2020; Rischin 2020).

Non–small cell lung cancer, locally advanced or metastatic

Non–small cell lung cancer, locally advanced or metastatic (first-line treatment): IV: 350 mg once every 3 weeks until disease progression or unacceptable toxicity (Sezer 2021). Note: Select patients for treatment based on PD-L1 expression (on ≥50% of tumor cells).

Dosing: Kidney Impairment: Adult

Renal impairment prior to treatment initiation: Note: Kidney function estimated by Cockcroft-Gault equation.

CrCl ≥21 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, CrCl ≥21 mL/minute had no clinically important effect on cemiplimab pharmacokinetics.

CrCl <21 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

Renal toxicity during treatment:

Immune-mediated nephritis with kidney dysfunction: If cemiplimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper.

Grade 2 or 3 increased serum creatinine: Withhold treatment; resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4 increased serum creatinine: Permanently discontinue cemiplimab.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild or moderate impairment (total bilirubin >1 up to 3 × ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, mild or moderate hepatic impairment had no clinically important effect on cemiplimab pharmacokinetics.

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Hepatotoxicity during treatment:

If cemiplimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Immune-mediated hepatitis without tumor involvement of the liver:

ALT or AST >3 up to 8 × ULN or total bilirubin >1.5 up to 3 × ULN: Withhold treatment; may resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper.

ALT or AST >8 × ULN or total bilirubin >3 × ULN: Permanently discontinue cemiplimab.

Immune-mediated hepatitis with tumor involvement of the liver:

Baseline ALT or AST >1 up to 3 × ULN and increases to >5 up to 10 × ULN or baseline ALT or AST >3 up to 5 × ULN and increases to >8 up to 10 × ULN: Withhold treatment; resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper. If ALT and AST are ≤ ULN at baseline, withhold or permanently discontinue cemiplimab based on recommendations for hepatitis without liver involvement (above).

ALT or AST >10 × ULN or total bilirubin >3 × ULN: Permanently discontinue cemiplimab.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

No dose reduction for cemiplimab is recommended.

Immune-mediated toxicities (general information): Withhold cemiplimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue cemiplimab for life-threatening (grade 4) adverse reactions, recurrent severe (grade 3) adverse reactions, or inability to reduce corticosteroid dose to ≤10 mg/day prednisone (or equivalent) within 12 weeks of corticosteroids. If cemiplimab requires treatment interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to grade 1 or lower, then follow with a corticosteroid taper (continue to taper over at least 1 month). If immune-mediated adverse reaction is not controlled with systemic corticosteroids, consider administration of other systemic immunosuppressants. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.

Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (ASCO [Schneider 2021]). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

Recommended Cemiplimab Dosage Modifications for Adverse Events

Adverse reaction

Severity

Cemiplimab modification

aSJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.

b Refer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

Immune-mediated adverse reactions

Cardiovascular toxicity: Myocarditis

Grade 2, 3, or 4

Permanently discontinue cemiplimab.

Dermatologic toxicity:

Mild or moderate nonexfoliative rash

May be managed with topical emollients and/or topical corticosteroids.

Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSa

Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Confirmed SJS, TEN, or DRESSa

Permanently discontinue cemiplimab.

Endocrinopathies

Grades 3 or 4

Withhold treatment until clinically stable or permanently discontinue cemiplimab depending on the severity.

Adrenal insufficiency, ≥ grade 2

Initiate symptomatic management (including hormone replacement as clinically indicated).

Diabetes, type 1

Initiate insulin as clinically indicated.

Hypophysitis

Withhold or discontinue cemiplimab (depending on the severity). Initiate hormone replacement therapy as clinically indicated.

Hyperthyroidism

Withhold or discontinue cemiplimab (depending on the severity). Initiate medical management as clinically indicated.

Hypothyroidism

Withhold cemiplimab (depending on the severity). Initiate thyroid hormone replacement therapy as clinically indicated.

GI adverse reactions: Colitis

Grade 2 or 3

Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4

Permanently discontinue cemiplimab.

Neurologic toxicities

Grade 2

Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 3 or 4

Permanently discontinue cemiplimab.

Ocular disorders: Vogt-Koyanagi-Harada-like syndrome

May require systemic corticosteroids to reduce the risk of permanent vision loss.

Pulmonary toxicity: Pneumonitis

Grade 2

Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 3 or 4

Permanently discontinue cemiplimab.

Other adverse reactions

Infusion-related reactions

Grade 1 or 2

Interrupt infusion or slow the infusion rate.

Grade 3 or 4

Permanently discontinue cemiplimab.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Libtayo: cemiplimab-rwlc 350 mg/7 mL (7 mL) [contains polysorbate 80]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Libtayo: 250 mg/5 mL (5 mL); 350 mg/7 mL (7 mL) [contains polysorbate 80]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Libtayo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf#page=29

Administration: Adult

IV: Infuse over 30 minutes through a 0.2 to 5 micron inline or add-on filter. Allow solution to reach room temperature prior to infusion. Monitor for infusion reactions (may require infusion rate reduction, infusion interruption, or discontinuation depending on the severity).

Use: Labeled Indications

Basal cell carcinoma, locally advanced or metastatic: Treatment of locally advanced and metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or when a hedgehog pathway inhibitor is not appropriate.

Cutaneous squamous cell carcinoma, metastatic or locally advanced: Treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation.

Non–small cell lung cancer, locally advanced or metastatic: First-line treatment of non–small cell lung cancer in patients whose tumors have high PD-L1 expression (Tumor Proportion Score ≥50%) as determined by an approved test, with no EGFR, ALK, or ROS1 aberrations, and locally advanced (in patients who are not candidates for surgical resection or definitive chemoradiation) or metastatic disease.

Use: Off-Label: Adult

Cervical carcinoma, recurrent or metastatic

Medication Safety Issues
Sound-alike/look-alike issues:

Cemiplimab may be confused with caplacizumab, cenegermin, certolizumab, cetuximab, dostarlimab, nivolumab.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences may be reported for non-FDA approved dosing.

>10%:

Cardiovascular: Hypertension (11%)

Dermatologic: Pruritus (18% to 20%), skin rash (15% to 31%)

Gastrointestinal: Constipation (11% to 13%), decreased appetite (10% to 14%), diarrhea (25%), nausea (12% to 21%)

Genitourinary: Urinary tract infection (12%)

Hematologic & oncologic: Anemia (11% to 15%; grades 3/4: ≤5%)

Nervous system: Fatigue (14% to 49%), headache (12%)

Neuromuscular & skeletal: Arthralgia (11%), musculoskeletal pain (24% to 33%)

Respiratory: Cough (11% to 14%), dyspnea (11%), pneumonia (11%), upper respiratory tract infection (15%)

1% to 10%:

Dermatologic: Cellulitis (grades 3/4: ≥2%), dermatologic disorder (2%; commonly occurred with drug reinitiation), skin infection (grades 3/4: ≥2%)

Endocrine & metabolic: Hypercalcemia (grades 3/4: 1% to 2%), hyperkalemia (grades 3/4: 4%), hypermagnesemia (grades 3/4: 2%), hyperthyroidism (3%), hypoalbuminemia (grades 3/4: 2%), hypocalcemia (grades 3/4: 4%), hypokalemia (grades 3/4: 2%), hyponatremia (grades 3/4: 3% to 6%), hypophosphatemia (grades 3/4: 2% to 4%), hypothyroidism (7% to 10%)

Gastrointestinal: Colitis (2%), vomiting (10%)

Hematologic & oncologic: Increased INR (grades 3/4: 2%), lymphocytopenia (grades 3/4: 2% to 9%), neoplasm (infected: >2%), prolonged partial thromboplastin time (grades 3/4: 2%)

Hepatic: Hepatitis (2%), increased serum alanine aminotransferase (grades 3/4: 3%), increased serum alkaline phosphatase (grades 3/4: 2%), increased serum aspartate aminotransferase (grades 3/4: 2% to 4%), increased serum bilirubin (grades 3/4: 2%)

Immunologic: Antibody development (2%)

Infection: Sepsis (grades 3/4: ≥2%)

Nervous system: Drowsiness (>2%)

Ophthalmic: Visual impairment (>2%)

Renal: Acute kidney injury (>2%), increased serum creatinine (grades 3/4: 1%)

Respiratory: Pneumonitis (3%)

<1%:

Cardiovascular: Myocarditis, pericarditis, vasculitis

Endocrine & metabolic: Adrenocortical insufficiency, hypoparathyroidism, hypophysitis, thyroiditis, type 1 diabetes mellitus (can be severe presenting as diabetic ketoacidosis)

Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase, pancreatitis, stomatitis

Hematologic & oncologic: Aplastic anemia, hemolytic anemia, immune thrombocytopenia, immunological signs and symptoms (hemophagocytic lymphohistiocytosis), lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis]), sarcoidosis

Hypersensitivity: Severe infusion related reaction (grade 3)

Immunologic: Organ transplant rejection (solid)

Infection: Systemic inflammatory response syndrome

Nervous system: Demyelinating disease, encephalitis, Guillain-Barre syndrome, meningitis (including aseptic meningitis), myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve)

Neuromuscular & skeletal: Arthritis, myelitis, myositis, polymyalgia rheumatica, polymyositis, rhabdomyolysis

Ophthalmic: Iritis, ophthalmic inflammation, uveitis

Renal: Nephritis

Frequency not defined:

Cardiovascular: Ischemic stroke

Dermatologic: Maculopapular rash, psoriasis, skin or other tissue necrosis

Gastrointestinal: Proctitis

Nervous system: Complex regional pain syndrome, confusion, lethargy

Neuromuscular & skeletal: Neck pain

Postmarketing:

Dermatologic: Pemphigoid (SITC [Brahmer 2021]), Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (SITC [Brahmer 2021])

Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])

Hematologic & oncologic: Neutropenia (SITC [Brahmer 2021]), pure red cell aplasia (SITC [Brahmer 2021])

Hepatic: Hepatotoxicity (Chalasani 2021)

Immunologic: Sjögren's syndrome (SITC [Brahmer 2021])

Neuromuscular & skeletal: Myalgia (SITC [Brahmer 2021])

Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021])

Miscellaneous: Infusion-related reaction (SITC [Brahmer 2021])

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to cemiplimab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse events (immune-mediated): PD-1/PD-L1 blockers (including cemiplimab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, may occur in any tissue or organ system and may affect more than one organ system simultaneously. Immune-mediated adverse reactions may occur at any time after initiating an anti-PD-L1/PD-1 monoclonal antibody. While immune-mediated adverse reactions generally manifest during treatment, they may also occur following cemiplimab discontinuation. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of anti-PD-1/PD-L1 monoclonal antibodies. If immune-mediated adverse reaction is suspected, initiate appropriate work-up to exclude alternate etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

• Dermatologic toxicity: Cemiplimab may cause immune-mediated rash or dermatitis. Immune-mediated dermatologic adverse reaction is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Grade 2 and 3 events have been reported. Exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have occurred with anti-PD-L1/PD-1 monoclonal antibodies. Depending on the severity, dermatologic adverse reactions may require treatment interruption or permanent discontinuation. Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Dermatologic adverse reactions led to treatment interruption or permanent discontinuation in a small percentage of patients. Immune-mediated dermatologic adverse reactions resolved in over two-thirds of patients, although nearly one-half of patients experienced recurrence of dermatologic toxicity upon reinitiation of cemiplimab.

• Endocrinopathies: Cemiplimab is associated with immune-mediated endocrinopathies.

– Adrenal insufficiency: Cemiplimab may cause primary or secondary adrenal insufficiency; grade 3 events have been reported. Adrenal insufficiency did not require treatment interruption or discontinuation; however, depending on the severity, withhold cemiplimab. Systemic corticosteroids were required in all patients with adrenal insufficiency; two-thirds of those patients remained on corticosteroids.

– Diabetes mellitus: Cemiplimab has been associated with type 1 diabetes mellitus (which may present with diabetic ketoacidosis) in a small percentage of patients, including grade 4 events, although treatment discontinuation was not required.

Hypophysitis: Cemiplimab may rarely cause immune-mediated hypophysitis (including rare grade 2 and 3 events). Hypophysitis may present with acute mass effect-associated symptoms such as headache, photophobia, or visual field defects. Hypophysitis may cause hypopituitarism. Systemic corticosteroids were required in two-thirds of patients.

Thyroid disorders: Cemiplimab may cause immune-mediated thyroid disorders. Hyperthyroidism occurred in a small percentage of patients, including grade 2 events. Discontinuation due to hyperthyroidism was not required, although treatment interruption was required in a small number of patients. Systemic corticosteroids were rarely required. Hyperthyroidism resolved in half of patients. Some patients requiring treatment interruption for hyperthyroidism reinitiated cemiplimab (after symptom improvement) and did not experience recurrence. Hypothyroidism has also occurred, including grade 2 events. Hypothyroidism may follow hyperthyroidism. Initiate hormone replacement for hypothyroidism as clinically indicated. Discontinuation due to hypothyroidism was rarely required, although treatment interruption was required in a small number of patients; systemic corticosteroids were not required in any patient with hypothyroidism. Hypothyroidism resolved in a small number of patients, although the majority of patients with hypothyroidism required long-term thyroid hormone replacement therapy. In patients who reinitiated cemiplimab after it was withheld for hypothyroidism (following symptom improvement), ongoing hormone replacement therapy was required. Thyroiditis occurred rarely, including grade 2 events; systemic corticosteroids were not required, although thyroiditis did not resolve. Increases or decreases in blood thyroid stimulating hormone have been observed.

• GI adverse reactions: Cemiplimab may cause immune-mediated colitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. The primary component of immune-mediated colitis was diarrhea. Immune-mediated colitis occurred in a small percentage of patients, including grade 2 and 3 events. Colitis led to permanent discontinuation or treatment interruption in a small number of patients. Systemic corticosteroids were required in all patients with colitis. Colitis resolved in over one-third of patients. Some patients requiring treatment interruption for colitis reinitiated cemiplimab, and colitis recurred in a majority of these patients. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis who received anti-PD-L1/PD-1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatitis: Cemiplimab may cause immune-mediated hepatitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Immune-mediated hepatitis occurred in a small percentage of patients, including grade 2 and higher events (some fatal). Hepatitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with hepatitis; some patients required additional immunosuppression (with mycophenolate). Hepatitis resolved in one-half of patients. Recurrence was not observed in patients who reinitiated cemiplimab (following symptom improvement).

• Infusion reactions: Severe infusion-related reactions (grade 3) have occurred (rarely) in patients receiving cemiplimab. Common symptoms of infusion reactions included nausea, fever, rash, and dyspnea.

• Nephrotoxicity: Cemiplimab may cause immune-mediated nephritis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Grade 2, 3, and fatal events have occurred in a small number of patients. Nephritis led to treatment interruption or permanent discontinuation rarely. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in almost all patients. Some patients requiring treatment interruption for nephritis reinitiated cemiplimab after symptom improvement, and none experienced recurrence.

• Ocular disorders: Ocular events, including uveitis, iritis, and other ocular inflammatory toxicities have been reported; some cases may be associated with retinal detachment. Various grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.

• Pneumonitis: Cemiplimab may cause immune-mediated pneumonitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. In patients who received other anti-PD-L1/PD-1 monoclonal antibodies, the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Grade 2 to 4 events have been observed. Pneumonitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in over half of patients. Of the patients who reinitiated cemiplimab (following symptom improvement), some experienced recurrence of pneumonitis.

• Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported rarely with cemiplimab or with other anti-PD-L1/PD-1 monoclonal antibodies (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitis, myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), and solid organ transplant rejection.

Disease-related concerns:

• Hematopoietic stem cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and HSCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HSCT.

• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Select patients for first-line treatment of locally advanced (unresectable) or metastatic non–small cell lung cancer based on PD-L1 expression (≥50%) on tumor cells. Information on approved tests for detection of PD-L1 expression may be found at http://www.fda.gov/companiondiagnostics.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Ketoconazole (Systemic): Immune Checkpoint Inhibitors may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy

Reproductive Considerations

Evaluate pregnancy status prior to therapy. Patients who could become pregnant should use effective contraception during therapy and for at least 4 months after the last cemiplimab dose.

Pregnancy Considerations

Cemiplimab is a recombinant human immunoglobulin (IgG4) monoclonal antibody; human IgG4 is known to cross the placenta. Based on the mechanism of action and information from animal reproduction studies, use of cemiplimab during pregnancy may cause fetal harm.

Breastfeeding Considerations

It is not known if cemiplimab is present in breast milk.

Due to the potential for adverse events in the breastfed infant, the manufacturer does not recommended breastfeeding during therapy or for at least 4 months after the last cemiplimab dose.

Monitoring Parameters

PD-L1 expression (for first-line treatment of metastatic or locally advanced nonsmall cell lung cancer). Evaluate serum chemistries, hepatic function tests, serum creatinine, and thyroid function tests (at baseline and periodically during treatment). Monitor blood glucose (for hyperglycemia). Evaluate pregnancy status (prior to therapy in patients who could become pregnant). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, dermatologic toxicity, diabetes mellitus, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), hepatitis, hypophysitis, ocular disorders, pneumonitis, thyroid disorders, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Additional suggested monitoring (ASCO [Schneider 2021): Prior to therapy: CBC with differential; creatine kinase; comprehensive clinical assessment including performance status, weight, body mass index, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms. During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections; screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks); CBC with differential; creatine kinase; monitor bone mineral density (with long-term therapy).

Mechanism of Action

Cemiplimab is a recombinant human IgG4 monoclonal antibody that inhibits programmed death-1 (PD-1) activity by binding to PD-1 and blocking the interactions with the ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of immune response, including anti-tumor response. PD-1 ligand upregulation may occur in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Blocking PD-1 activity has resulted in decreased tumor growth.

Pharmacokinetics

Distribution: Vd: 5.3 L.

Half-life elimination: ~20 days.

Excretion: Clearance: First dose: 0.29 L/day; steady state: 0.2 L/day.

Pricing: US

Solution (Libtayo Intravenous)

350 mg/7 mL (per mL): $1,647.37

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Libtayo (AT, BR, CZ, DE, DK, EE, FR, GB, HR, HU, IN, KR, LT, LV, NL, NO, PT, SK)


For country abbreviations used in Lexicomp (show table)
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  2. Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. doi:10.1136/jitc-2021-002435 [PubMed 34172516]
  3. Centers for Disease Control and Prevention (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. [PubMed 6423951]
  4. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice parameters committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]
  5. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  6. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  7. Isik B, Alexander MP, Manohar S, et al. Biomarkers, clinical features and rechallenge for immune checkpoint inhibitor renal immune-related adverse events. Kidney International Reports (2021). doi: https://doi.org/10.1016/j.ekir.2021.01.013
  8. Libtayo (cemiplimab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; February 2021.
  9. Libtayo (cemiplimab) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; March 2022.
  10. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  11. Migden MR, Khushalani NI, Chang ALS, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020;21(2):294-305. doi:10.1016/S1470-2045(19)30728-4 [PubMed 31952975]
  12. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341-351. doi:10.1056/NEJMoa1805131 [PubMed 29863979]
  13. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124 [PubMed 33144515]
  14. Rischin D, Migden MR, Lim AM, et al. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing. J Immunother Cancer. 2020;8(1):e000775. doi:10.1136/jitc-2020-000775 [PubMed 32554615]
  15. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440 [PubMed 34724392]
  16. Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2 [PubMed 33581821]
  17. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8960):1312-1313. [PubMed 7746084]
  18. Tewari KS, Monk BJ, Vergote I, et al; Investigators for GOG protocol 3016 and ENGOT protocol En-Cx9. Survival with cemiplimab in recurrent cervical cancer. N Engl J Med. 2022;386(6):544-555. doi:10.1056/NEJMoa2112187 [PubMed 35139273]
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