Cemiplimab, a fully human anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1, 3, 6
Cutaneous Squamous Cell Carcinoma
Cemiplimab-rwlc is used for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy.1, 2
The current indication for cemiplimab-rwlc is based principally on the combined results of an open-label, multicenter, nonrandomized, phase 1 study (Study 1423) and an open-label, multicenter, nonrandomized, multicohort phase 2 study (Study 1540) in 108 adults with metastatic or locally advanced cutaneous squamous cell carcinoma who were not candidates for curative surgery or radiation therapy.1, 2 In these studies, patients received cemiplimab-rwlc 3 mg/kg administered as an IV infusion every 2 weeks for up to 48 or 96 weeks.1, 2 Treatment was continued for the specified duration or until the occurrence of unacceptable toxicity or disease progression.1 The primary measures of efficacy were objective response rate and duration of response as evaluated by an independent central review committee.1 Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) in patients without externally visible target lesions or by a composite end point that included radiographic assessment according to RECIST and digital medical images according to World Health Organization (WHO) criteria in patients with externally visible target lesions.1, 2
The median age of patients in the combined analysis of Study 1423 and Study 1540 was 71 years (range: 38-96 years); 97% were white, 85% were male, 50% had received at least one prior systemic therapy, 96% had previously undergone surgery, and 79% had received prior radiation therapy.1 All patients enrolled in the studies had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1 Most patients (69%) had metastatic cutaneous squamous cell carcinoma and 31% had locally advanced disease.1 Among patients with metastatic cutaneous squamous cell carcinoma, 69% had distant metastases and 31% had nodal metastases only.1 These studies excluded patients with active autoimmune disease that required systemic therapy in the past 5 years; those who had received a solid organ transplant; those who had received prior therapy with other anti-programmed-death 1 (anti-PD-1) or anti-PD ligand 1 (anti-PD-L1) antibodies or other immune-checkpoint inhibitors; those with an ECOG performance status of 2 or greater; and those with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.1
At a median follow-up of 8.9 months, the objective response rate was 47.2%;1 complete responses were achieved in 3.7% of patients.1 In the cohort of patients with metastatic cutaneous squamous cell carcinoma at a median follow-up of 8.1 months, the objective response rate was 46.7%; complete responses were achieved in 5.3% of patients.1, 2 In the cohort of patients with locally advanced cutaneous squamous cell carcinoma at a median follow-up 10.2 months, the objective response rate was 48.5%; there were no complete responses.1 At the time of analysis, the overall median duration of response had not been reached; however, 60 or 63% of patients with metastatic or locally advanced cutaneous squamous cell carcinoma, respectively, had durable responses of 6 months or more.1
Because immune-mediated adverse effects may occur in any organ system or tissue, the manufacturer states that blood chemistries and liver and thyroid function tests should be assessed prior to initiation of cemiplimab therapy and periodically during therapy.1
Cemiplimab-rwlc can only be obtained through a limited network of speciality distributors or pharmacies.4 Clinicians may contact the manufacturer (Regeneron) at 877-542-8296 or consult the Libtayo® website ([Web]) for specific ordering and availability information.4
Cemiplimab-rwlc is administered by IV infusion over 30 minutes.1
Unopened vials of cemiplimab-rwlc injection concentrate should be stored at 2-8°C in the original carton to protect the drug from light, and should not be frozen or shaken.1
Cemiplimab-rwlc injection concentrate must be diluted prior to administration.1 Prior to administration, cemiplimab-rwlc injection concentrate should be inspected visually for particulate matter and discoloration.1 The undiluted solution should be clear to slightly opalescent and colorless to pale yellow; the solution should not be used if it is cloudy or discolored or if foreign particles other than translucent to white particles are present.1 Cemiplimab-rwlc is diluted by adding 7 mL of cemiplimab-rwlc injection concentrate (containing 50 mg/mL) to an appropriate volume of 0.9% sodium chloride or 5% dextrose injection to a final concentration of 1-20 mg/mL.1 The diluted solution should be mixed by gentle inversion and should not be shaken.1 Cemiplimab-rwlc should be administered through a sterile, 0.2- to 5-µm inline or add-on filter.1
Diluted solutions of the drug are stable for up to 8 hours after dilution (including infusion time) when stored at room temperature (up to 25°C) or up to 24 hours after dilution (including infusion time) when stored under refrigeration (2-8°C); diluted solutions of the drug should be brought to room temperature prior to administration.1 Diluted solutions of the drug should not be frozen.1
Cemiplimab-rwlc injection concentrate is intended for single use only; any unused portion in the vial should be discarded.1
Cutaneous Squamous Cell Carcinoma
For the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma, the recommended adult dosage of cemiplimab-rwlc is 350 mg administered every 3 weeks.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Therapy Interruption for Toxicity
If immune-mediated adverse effects occur, temporary or permanent discontinuance of cemiplimab may be required based on the severity of the reaction.1
Cemiplimab should be permanently discontinued in patients experiencing recurrent grade 3 or 4 immune-mediated adverse effects or persistent grade 2 or 3 immune-mediated adverse effects lasting 12 weeks or longer, and in those requiring a corticosteroid dosage of 10 mg or more of prednisone daily (or equivalent) for 12 weeks or longer.1
If grade 2 immune-mediated pneumonitis occurs, cemiplimab therapy should be interrupted.1 Once the toxicity has resolved to grade 0 or 1, cemiplimab therapy may be resumed following completion of the corticosteroid taper.1 (See Immune-mediated Pneumonitis under Cautions: Warnings/Precautions.)
If grade 3 or 4 immune-mediated pneumonitis occurs, cemiplimab therapy should be permanently discontinued.1
If grade 2 or 3 immune-mediated colitis occurs, cemiplimab therapy should be interrupted.1 Once the toxicity has resolved to grade 0 or 1, cemiplimab therapy may be resumed following completion of the corticosteroid taper.1 (See Immune-mediated GI Effects under Cautions: Warnings/Precautions.)
If grade 4 immune-mediated colitis occurs, cemiplimab therapy should be permanently discontinued.1
Immune-mediated Hepatic Effects
For serum aminotransferase (ALT or AST) elevations exceeding 3 times but not more than 10 times the upper limit of normal (ULN) or total bilirubin concentrations exceeding the ULN but not more than 3 times the ULN, cemiplimab therapy should be interrupted.1 Once the toxicity has resolved to grade 0 or 1, cemiplimab therapy may be resumed following completion of the corticosteroid taper.1 (See Immune-mediated Hepatic Effects under Cautions: Warnings/Precautions.)
For ALT or AST elevations exceeding 10 times the ULN or total bilirubin concentrations exceeding 3 times the ULN, cemiplimab therapy should be permanently discontinued.1
Immune-mediated Endocrine Effects
If grade 2-4 endocrinopathies (e.g., adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, diabetes mellitus) occur, cemiplimab therapy should be interrupted if clinically necessary.1 (See Immune-mediated Endocrine Effects under Cautions: Warnings/Precautions.)
Other Immune-mediated Adverse Effects
If any other grade 3 immune-mediated adverse effects involving a major organ occur, cemiplimab therapy should be interrupted.1 Once the toxicity has resolved to grade 0 or 1, cemiplimab therapy may be resumed following completion of the corticosteroid taper.1 (See Other Immune-mediated Effects under Cautions: Warnings/Precautions.)
If any other grade 4 immune-mediated adverse effects involving a major organ occur, cemiplimab therapy should be permanently discontinued.1
If grade 1 or 2 infusion-related reactions occur, the infusion should be interrupted or the infusion rate should be reduced.1 (See Infusion-related Effects under Cautions: Warnings/Precautions.)
If grade 3 or 4 infusion-related reactions occur, cemiplimab therapy should be permanently discontinued.1
The manufacturer makes no special population dosage recommendations at this time.1 (See Specific Populations under Cautions: Warnings/Precautions.)
The manufacturer states there are no known contraindications to the use of cemiplimab.1
Immune-mediated pneumonitis, sometimes fatal, has occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-programmed-death 1 (anti-PD-1) and anti-PD ligand 1 (anti-PD-L1) antibodies, but also may occur following discontinuance of the drug.1
In clinical trials, immune-mediated pneumonitis occurred in 2.4% of 534 patients receiving cemiplimab-rwlc and was fatal in 0.2% of patients.1 Grade 2 or 3 immune-mediated pneumonitis was reported in 2% of patients.1 Cemiplimab-rwlc was permanently discontinued because of immune-mediated pneumonitis in 1.3% of patients receiving the drug.1 All patients experiencing immune-mediated pneumonitis received systemic corticosteroid therapy and 85% received high-dose corticosteroid therapy (40 mg or more of prednisone daily [or equivalent]).1 Immune-mediated pneumonitis resolved in 62% of patients.1
Patients receiving cemiplimab should be monitored for manifestations of pneumonitis.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated pneumonitis occurs during therapy with the drug.1 (See Immune-mediated Pneumonitis under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) In patients who develop grade 2 or greater pneumonitis, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once symptoms improve to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated pneumonitis inadequately controlled with systemic corticosteroid therapy.1
Immune-mediated colitis has occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
In clinical trials, grade 2 or 3 immune-mediated colitis occurred in 0.9% of 534 patients receiving cemiplimab-rwlc.1 Cemiplimab-rwlc was permanently discontinued because of immune-mediated colitis in 0.2% of patients.1 All patients experiencing immune-mediated colitis received systemic corticosteroid therapy and 60% received high-dose corticosteroid therapy (40 mg or more of prednisone daily [or equivalent]).1 Immune-mediated colitis resolved in 80% of patients.1
Patients receiving cemiplimab should be monitored for manifestations of colitis.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated colitis occurs during therapy with the drug.1 (See Immune-mediated GI Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) In patients who develop grade 2 or greater colitis, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once symptoms improve to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated colitis inadequately controlled with systemic corticosteroid therapy.1
Immune-mediated Hepatic Effects
Immune-mediated hepatitis, sometimes fatal, has occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
In clinical trials, immune-mediated hepatitis occurred in 2.1% of 534 patients receiving cemiplimab-rwlc and was fatal in 0.2% of patients.1 Grade 3 or 4 immune-mediated hepatitis was reported in 1.9% of patients.1 Cemiplimab-rwlc was permanently discontinued because of immune-mediated hepatitis in 0.9% of patients receiving the drug.1 All patients experiencing immune-mediated hepatitis received systemic corticosteroid therapy and 91% received high-dose corticosteroid therapy (40 mg or more of prednisone daily [or equivalent]).1 Immune-mediated hepatitis resolved in 64% of patients.1
Patients receiving cemiplimab should be monitored for manifestations of hepatitis.1 Liver function tests should be assessed prior to initiation of cemiplimab therapy and periodically during therapy.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated hepatitis occurs during therapy with the drug.1 (See Immune-mediated Hepatic Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) If serum aminotransferase (ALT or AST) elevations exceeding 3 times the upper limit of normal (ULN) (i.e., grade 2 or greater) or total bilirubin concentrations exceeding the ULN occur, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once the toxicity improves to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated hepatitis inadequately controlled with systemic corticosteroid therapy.1
Immune-mediated Endocrine Effects
Immune-mediated endocrinopathies, such as adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid dysfunction (i.e., hypothyroidism, hyperthyroidism), and diabetes mellitus (including ketoacidosis), have occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated endocrinopathies occur during therapy with the drug.1 (See Immune-mediated Endocrine Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) Certain grade 2 or greater endocrinopathies may require initiation of systemic corticosteroid therapy (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once the toxicity improves to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing certain immune-mediated endocrinopathies inadequately controlled with systemic corticosteroid therapy.1 Hormone replacement therapy, including antidiabetic therapy (e.g., insulin), also should be administered as clinically indicated.1
In clinical trials, grade 2 or 3 immune-mediated adrenal insufficiency occurred in 0.4% of 534 patients receiving cemiplimab-rwlc.1
Patients receiving cemiplimab should be monitored for signs and symptoms of adrenal insufficiency.1
In clinical trials, grade 3 immune-mediated hypophysitis occurred in 1 of 534 patients (0.2%) receiving cemiplimab-rwlc.1
Patients receiving cemiplimab should be monitored for manifestations of hypophysitis.1
In clinical trials, immune-mediated hypothyroidism occurred in 6% of 534 patients receiving cemiplimab-rwlc therapy and was grade 3 in 0.2% of patients.1 None of the patients experiencing immune-mediated hypothyroidism were able to discontinue thyroid hormone replacement therapy.1
In clinical trials, immune-mediated hyperthyroidism occurred in 1.5% of 534 patients receiving cemiplimab-rwlc and was grade 2 or 3 in 0.6% of patients.1 Immune-mediated hyperthyroidism resolved in 38% of patients.1
Patients receiving cemiplimab should be monitored for manifestations of thyroid dysfunction.1 Thyroid function should be evaluated prior to initiation of cemiplimab therapy and periodically during therapy.1
In clinical trials, grade 3 or 4 immune-mediated type 1 diabetes mellitus and ketoacidosis occurred in 0.7% of 534 patients receiving cemiplimab-rwlc.1 Cemiplimab-rwlc was permanently discontinued because of immune-mediated type 1 diabetes mellitus in 0.2% of patients receiving the drug.1
Patients should be monitored for manifestations of diabetes mellitus.1 Blood glucose concentrations should be assessed prior to initiation of cemiplimab therapy and periodically during therapy.1
Immune-mediated nephritis has occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
In clinical trials, grade 2 or 3 immune-mediated nephritis occurred in 0.6% of 534 patients receiving cemiplimab-rwlc.1 Cemiplimab-rwlc was permanently discontinued because of immune-mediated nephritis in 0.2% of patients receiving the drug.1 All patients experiencing immune-mediated nephritis received systemic corticosteroid therapy and 67% received high-dose corticosteroid therapy (40 mg or more of prednisone daily [or equivalent]).1 Complete resolution of immune-mediated nephritis occurred in all patients.1
Patients receiving cemiplimab should be monitored for changes in renal function.1 Serum creatinine should be assessed prior to initiation of cemiplimab therapy and periodically during therapy.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated nephritis occurs.1 (See Other Immune-mediated Adverse Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) If grade 2 or greater nephritis occurs, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once the toxicity improves to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated nephritis inadequately controlled with systemic corticosteroid therapy.1
Immune-mediated Dermatologic Effects
Immune-mediated dermatologic reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and pemphigoid, have occurred in patients receiving cemiplimab therapy.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
In clinical trials, grade 2 or 3 immune-mediated dermatologic reactions, including erythema multiforme and pemphigoid, occurred in 1.7% of 534 patients receiving cemiplimab-rwlc.1 Stevens-Johnson syndrome and toxic epidermal necrolysis also have occurred in patients receiving anti-PD-1 and anti-PD-L1 antibodies, including cemiplimab-rwlc.1 All patients experiencing immune-mediated dermatologic reactions received systemic corticosteroid therapy and 89% received high-dose corticosteroid therapy (40 mg or more of prednisone daily [or equivalent]).1 Immune-mediated dermatologic reactions resolved in 33% of patients.1 Following reinitiation of cemiplimab-rwlc, immune-mediated dermatologic reactions recurred in approximately 22% of patients.1
Patients receiving cemiplimab should be monitored for dermatologic reactions.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated dermatologic reactions occur.1 (See Other Immune-mediated Adverse Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) If grade 2 or greater dermatologic reactions occur, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once the toxicity improves to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated dermatologic reactions inadequately controlled with systemic corticosteroid therapy.1
Other immune-mediated adverse effects, sometimes severe or fatal, including meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitides, pancreatitis (including elevations in serum amylase and lipase concentrations), gastritis, duodenitis, myositis, rhabomyolysis and associated sequelae (e.g., renal failure), arthritis, polymyalgia rheumatica, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis, sarcoidosis, and immune thrombocytopenic purpura, were observed in less than 1% of 534 patients receiving cemiplimab-rwlc in clinical trials or have been reported in patients receiving other anti-PD-1 or anti-PD-L1 antibodies.1 Immune-mediated rejection of solid organ transplants also was reported in patients who received cemiplimab.1 Immune-mediated adverse effects generally occur during therapy with anti-PD-1 and anti-PD-L1 antibodies, but also may occur following discontinuance of the drug.1
Ocular inflammatory toxicity (e.g., uveitis, iritis), sometimes associated with retinal detachment, visual impairment, or blindness, also has been reported rarely in patients receiving cemiplimab-rwlc in clinical trials.1 If uveitis occurs in conjunction with other immune-mediated adverse effects, a Vogt-Koyanagi-Harada-like syndrome should be considered.1 Systemic corticosteroid therapy may be required to reduce the risk of permanent vision loss.1
Patients receiving cemiplimab should be monitored for immune-mediated adverse effects.1 Temporary interruption or discontinuance of cemiplimab may be necessary if immune-mediated adverse effects occur.1 (See Other Immune-mediated Adverse Effects under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.) If grade 2 or greater adverse effects occur, systemic corticosteroid therapy should be initiated (1-2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage over 1 month once the toxicity improves to grade 0 or 1.1 Systemic immunosuppressive therapy may be considered in patients experiencing immune-mediated adverse effects inadequately controlled with systemic corticosteroid therapy.1
Severe infusion-related reactions have occurred in 0.2% of patients receiving cemiplimab-rwlc.1
Patients receiving cemiplimab should be monitored for manifestations of infusion-related reactions.1 In patients experiencing infusion-related reactions, interruption of the infusion, reduction in the infusion rate, or permanent discontinuance of the drug may be necessary.1 (See Infusion-related Reactions under Dosage: Therapy Interruption for Toxicity, in Dosage and Administration.)
Fetal/Neonatal Morbidity and Mortality
Cemiplimab may cause fetal harm if administered to pregnant women.1 Blockade of signaling of the PD-1 and PD-L1 pathway in animals has been shown to disrupt maternal immune tolerance to the fetus and has been associated with increased fetal loss and immune-mediated disorders.1 Therefore, inhibition of this pathway by cemiplimab may increase the risk of fetal loss (e.g., abortion, stillbirth).1 Human immunoglobulin G4 (IgG4) has been shown to cross the placenta; therefore, fetal exposure to cemiplimab may occur and increase the risk of immune-mediated disorders or alter normal immune response of the developing fetus.1
Pregnancy should be avoided during cemiplimab therapy.1 The manufacturer recommends confirmation of pregnancy status prior to initiation of cemiplimab.1 Women of childbearing potential should be advised to use an effective method of contraception while receiving cemiplimab and for at least 4 months after the last dose.1 If cemiplimab is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard.1
There is a potential for immunogenicity with cemiplimab therapy.1 Development of anti-cemiplimab antibodies was detected by electrochemiluminescence (ECL) in 5 of 398 patients (1.3%) receiving cemiplimab-rwlc.1, 3 Among the 5 patients who tested positive for antibody formation during treatment, one patient had persistently positive test results and none of the patients had evidence of neutralizing antibodies to the drug.1, 3 Data are insufficient to determine the clinical importance of such anti-drug antibodies; however, no effects of antibody formation on pharmacokinetics or safety (i.e., infusion-related reactions) of the drug were observed.1, 3
Cemiplimab may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)
It is not known whether cemiplimab is distributed into human milk.1 Because many drugs are distributed into human milk and because of the potential for serious adverse reactions to cemiplimab in nursing infants, women should be advised to discontinue nursing during cemiplimab therapy and for at least 4 months after the last dose.1 The effects of the drug on nursing infants or on milk production are unknown.1
Safety and efficacy of cemiplimab have not been established in pediatric patients.1
In clinical trials evaluating cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma, 72% of patients were 65 years of age or older and 37% were 75 years of age or older.1 No overall differences in safety or efficacy were observed between geriatric patients and younger adults.1
Systemic exposure of cemiplimab-rwlc was unaffected following administration of the drug in individuals with total bilirubin concentrations of 0.02-2.63 mg/dL.1 Cemiplimab has not been studied in patients with moderate or severe hepatic impairment.1
Systemic exposure of cemiplimab-rwlc was unaffected following administration of the drug in individuals with creatinine clearance of 25 mL/minute or greater.1
Adverse effects reported in 10% or more of patients receiving cemiplimab-rwlc for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma include fatigue,1, 2 rash,1, 2 diarrhea,1, 2 nausea,1, 2 musculoskeletal pain,1 pruritus,1, 2 cough,2 headache,2 constipation,1, 2 dry skin,2 vomiting,2 and decreased appetite.1, 2 Grade 3 or 4 laboratory abnormalities reported in 1% or more of patients receiving cemiplimab-rwlc for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma include lymphopenia,1 hypophosphatemia,1 elevated concentrations of aspartate aminotransferase (AST),1 hyponatremia,1 increased international normalized ratio (INR),1 anemia,1, 2 hypoalbuminemia,1 and hypercalcemia.1
Cemiplimab, a fully human anti-programmed-death receptor-1 (anti-PD-1) monoclonal antibody, is an antineoplastic agent.1, 6 The drug is an IgG4 immunoglobulin.1
Cemiplimab is highly selective for PD-1, an immune-checkpoint receptor expressed on activated T cells, monocytes, B cells, natural killer (NK) T cells, and dendritic cells.1, 2, 3, 5, 6, 7, 8, 9 Overexpression of PD-1 ligands on the surface of tumor cells results in activation of PD-1 and suppression of cytotoxic T-cell activity.1, 7, 10, 11, 12 Cemiplimab blocks the interaction between PD-1 and its ligands, resulting in enhanced immune response, including enhanced antitumor immune response.1, 3 The drug also has been shown to reduce tumor growth in syngeneic mouse tumor models.1
Cemiplimab-rwlc exhibits linear and dose-proportional pharmacokinetics over the dosage range of 1-10 mg/kg IV every 2 weeks and at a dosage of 350 mg IV every 3 weeks.1 Following repeated doses of cemiplimab-rwlc 350 mg IV every 3 weeks, steady-state concentrations are reached by approximately 4 months.1 Clearance of cemiplimab-rwlc is approximately 34% lower at steady state than following the initial dose.1 The elimination half-life of cemiplimab-rwlc is 19 days.1
Systemic exposure to cemiplimab-rwlc does not appear to be affected by age (range: 27-96 years), gender, body weight (range: 31-156 kg), race, cancer type, or serum albumin concentration (2.2-4.8 g/dL).1
Importance of advising patients to read the manufacturer's medication guide.1
Risk of immune-mediated pneumonitis.1 Importance of informing clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.1
Risk of immune-mediated colitis.1 Importance of informing clinician immediately if diarrhea, severe abdominal pain, or changes in stool occur.1
Risk of immune-mediated hepatitis.1 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.1
Risk of immune-mediated endocrine effects.1 Importance of informing clinician immediately if signs and symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or diabetes mellitus occur.1
Risk of immune-mediated nephritis or renal dysfunction.1 Importance of informing clinician immediately if signs and symptoms of nephritis (e.g., decreased urine output, hematuria, peripheral edema, lack of appetite) occur.1
Risk of immune-mediated rash.1 Importance of informing clinician immediately if a new rash develops.1
Risk of infusion-related reactions.1 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.1
Risk of fetal harm.1 Necessity of advising women of childbearing potential that they should use an effective method of contraception while receiving the drug and for at least 4 months after the last dose.1 Importance of women informing clinicians if they are or plan to become pregnant.1 If pregnancy occurs, advise pregnant women of potential risk to the fetus.1
Importance of advising women to avoid breast-feeding while receiving cemiplimab therapy and for at least 4 months after the last dose.1
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).1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Cemiplimab-rwlc can only be obtained through a limited network of speciality distributors or specialty pharmacies.4 (See Restricted Distribution under Dosage and Administration: General.)
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 26, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Regeneron Pharmaceuticals, Inc. Libtayo® (cemiplimab-rwlc) injection for intravenous use prescribing information. Tarrytown, NY; 2019 Mar.
2. Migden MR, Rischin D, Schmults CD et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med . 2018; 379:341-351. [PubMed 29863979]
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 761097Orig1s000: Multi-discipline review. From FDA website. [Web]
4. Regeneron Pharmaceuticals, Inc., and sanofi-aventis U.S. LLC. Libtayo® Surround product acquisition. Libtayo® Surround patient access and reimbursement support program website. 2018 Sep. Accessed 2019 April 10. [Web]
5. Markham A, Duggan S. Cemiplimab: First Global Approval. Drugs . 2018; 78:1841-1846. [PubMed 30456447]
6. Falchook GS, Leidner R, Stankevich E et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer . 2016; 4:70. [PubMed 27879972]
7. Davies M. New modalities of cancer treatment for NSCLC: focus on immunotherapy. Cancer Manag Res . 2014; 6:63-75. [PubMedCentral][PubMed 24520205]
8. Poole RM. Pembrolizumab: first global approval. Drugs . 2014; 74:1973-81. [PubMed 25331768]
9. Deeks ED. Nivolumab: a review of its use in patients with malignant melanoma. Drugs . 2014; 74:1233-9. [PubMed 25022950]
10. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 125554Orig1s000: Summary review. From FDA website. [Web]
11. Lu J, Lee-Gabel L, Nadeau MC et al. Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J Oncol Pharm Pract . 2014; :. [PubMed 24917416]
12. Luke JJ, Ott P. PD-1 pathway inhibitors: The next generation of immunotherapy for advanced melanoma. Oncotarget . 2015; :. [PubMedCentral][PubMed 25682878]