Cemiplimab is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in adult patients who are not candidates for curative surgery or radiation, for locally advanced or metastatic basal cell carcinoma in adult patients who were previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate, and for locally advanced or metastatic non-small cell lung cancer as monotherapy in patients whose tumors have high PD-L1 expression, and in combination with platinum-based chemotherapy regardless of PD-L1 status. Immune-mediated adverse reactions including colitis, pneumonitis, hepatitis, endocrinopathies, and nephritis have been reported with cemiplimab therapy; treatment with high-dose corticosteroids may be necessary in patients who develop immune-mediated toxicity.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Minimal
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Cemiplimab (50 mg/mL vial) is available as a clear to slightly opalescent, colorless to pale yellow solution that may contain trace amounts of translucent to white particles.
-Discard the vial if the solution is cloudy, discolored, or contains particulate matter other than the trace amounts of particles.
-Do not shake the vial.
Dilution:
-Withdraw the required amount/volume of drug from the vial and dilute in 0.9% Sodium chloride injection or 5% Dextrose injection to a final concentration between 1 and 20 mg/mL; mix by gentle inversion and do not shake.
-Discard any unused drug left in the vial.
-Storage following dilution: Store at room temperature (up to 25 degrees C or 77 degrees F) for up to 8 hours or refrigerated (2 to 8 degrees C; 36 to 46 degrees F) for up to 10 days from the time of dilution. Do not freeze.
Intravenous (IV) Infusion:
-If refrigerated, allow the diluted solution to warm to room temperature prior to administration.
-Administer the diluted solution IV over 30 minutes through a sterile, in-line or add-on 0.2-micron to 5-micron filter.
Immune-mediated reactions have been reported with programmed death-receptor 1/PD-ligand 1 (PD1/PD-L1) inhibitors, including cemiplimab; some cases were severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity. Immune reactions may occur in any organ system or tissue during therapy or after therapy is discontinued. Monitor patients for signs and symptoms of immune-mediated reactions. Obtain liver function tests, serum creatinine, and thyroid function tests prior to and periodically during therapy. Initiate appropriate workup to exclude alternative etiologies, particularly infectious etiologies. If an immune-mediated reaction is confirmed, begin medical management promptly; obtain a specialty consultation as appropriate. If cemiplimab is held or discontinued, administer systemic corticosteroid therapy (i.e., 1 to 2 mg/kg per day of prednisone or equivalent) until the toxicity improves to grade 1 or less. When the toxicity improves to grade 1 or less, begin a steroid taper over at least 1 month. If the immune-mediated toxicity is not improved with systemic corticosteroids, consider administering other systemic immunosuppressants.
Immune-mediated neurotoxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, and autoimmune neuropathy; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Immune-mediated pneumonitis occurred in 2.6% (grade 3 or 4, 0.9%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Fatal pneumonitis occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Cough including upper airway cough syndrome (12% or less) and dyspnea including exertional dyspnea (14% or less; grade 3 or 4, 2.2% or less) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy. Fatal acute respiratory distress syndrome (ARDS) occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial.
Immune-mediated musculoskeletal toxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, and polymyalgia rheumatica; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Fatigue occurred in 14% to 50% (grade 3 or 4, 1.1% to 4.3%) of patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials. The term fatigue included asthenia and malaise.
Immune-mediated colitis occurred in 2% (grade 3, 0.8%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Additionally, fatal cachexia worsening due to colitis occurred in 0.7% of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary. Consider repeating the infectious workup to exclude alternative etiologies in cemiplimab-treated patients who have corticosteroid-refractory immune-mediated colitis.
Diarrhea including enterocolitis (11% to 33%; grade 3 or 4, 1.1% to 4.3%), abdominal pain (12% or less; grade 3 or 4, 1.4% or less), nausea (13% to 25%; grade 3 or 4, 0.7% or less), constipation (12% to 14%; grade 3 or 4, 0.3% to 0.7%), vomiting including hematemesis (12% or less; grade 3 or 4, 0.6% or less), and decreased appetite/anorexia (11% to 17%; grade 3 or 4, 0.6% to 1.4%) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy.
Immune-mediated gastrointestinal toxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included gastritis, duodenitis, and stomatitis; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Immune-mediated cardiotoxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included myocarditis, pericarditis, and vasculitis; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Immune-mediated ocular toxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included uveitis, iritis, and other ocular inflammation toxicity; some cases were associated with retinal detachment. Visual impairment including vision loss/blindness may occur. Grade 3 or 4 visual impairment occurred in more than 2% of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a diagnosis of Vogt-Koyanagi-Harada syndrome. Patients may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.
Immune-mediated hepatitis occurred in 2.4% (grade 3 or 4, 1.9%, fatal, less than 0.1%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Fatal hepatitis occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. Monitor hepatic function (e.g., liver function tests, bilirubin) during therapy. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Elevated hepatic enzymes including grade 3 or 4 increased ALT (3% or less), AST (3.9% or less), and alkaline phosphatase (2.4% or less) levels and hyperbilirubinemia (2.1% or less) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy. Liver function abnormalities occurred in 10% (grade 3 or 4, 1.4%) of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. The term liver function abnormalities included increased ALT, AST, alkaline phosphatase, gamma-glutamyltransferase, and bilirubin levels.
Grade 3 immune-mediated primary or secondary adrenal/adrenocortical insufficiency occurred in 0.5% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with hormone replacement/endocrine therapy or systemic corticosteroids may be necessary.
Immune-mediated hyperthyroidism occurred in 3% (grade 3, less than 0.1%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Decreased blood thyroid stimulating hormone level was also reported. Monitor thyroid function tests during therapy. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with endocrine therapy/antithyroid agents or systemic corticosteroids may be necessary.
Grade 4 immune-mediated diabetes mellitus occurred in 1 patient (less than 0.1%) who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Patients may present with diabetic ketoacidosis. Grade 3 or 4 hyperglycemia was reported in 4% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. Monitor patients for signs and symptoms of diabetes including blood glucose levels during therapy. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with insulin may be necessary.
Immune-mediated interstitial nephritis was reported in 0.7% (grade 3, less than 0.1%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281); additionally, less than 0.1% of patients had a fatal outcome. Monitor renal function during therapy. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Nephrotoxicity including grade 3 or 4 increased serum creatinine level (2% or less) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy. Acute kidney injury occurred in 14% of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. The term acute kidney injury included increased serum creatinine level, renal failure or renal impairment, decreased glomerular filtration rate, and toxic nephropathy.
Immune-related dermatologic reactions including rash or dermatitis occurred in 1.9% (grade 3, 0.9%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Exfoliative dermatitis including Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN) has occurred with PD1/PD-L1-blocking antibodies. Mild to moderate non-exfoliative rashes may respond to topical emollients and/or topical corticosteroids. Treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary to treat exfoliative rashes. Rash was reported in 13% to 34% (grade 3 or 4, 0.7% to 1.7%) of patients who received cemiplimab as monotherapy or in combination with platinum-based chemotherapy. The term rash included maculopapular rash, atopic dermatitis, contact dermatitis, autoimmune/immune-mediated dermatitis, eczema, bullous rash/dermatitis, erythematous rash or erythema, acneiform rash/dermatitis, psoriasis, blister, pemphigoid, urticaria, exfoliative rash, and lichen planus/lichen planus-like eruption.
Pruritus (22% or less; grade 3 or 4, 0.3% or less) and actinic keratosis (10% or less) occurred in patients who received cemiplimab as monotherapy in clinical trials. Alopecia occurred in 37% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial.
Severe or life-threatening infusion-related reactions occurred in 0.2% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Reaction symptoms included nausea, fever, and vomiting. Monitor patients for signs and symptoms of infusion reactions. Hold, slow the rate of, or permanently discontinue cemiplimab depending on toxicity severity.
Musculoskeletal pain occurred in 26% to 36% (grade 3 or 4, 0.6% to 2.9%) of patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials. The term musculoskeletal pain included arthralgia, back pain, myalgia, polyarthritis, pain in extremity, neck pain, non-cardiac chest pain/musculoskeletal chest pain, arthritis, musculoskeletal stiffness, bone pain, and spinal pain.
Anemia (15% or less; grade 3 or 4, 0.7% to 10%) and lymphopenia (grade 3 or 4, 2.9% to 7%) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials. Grade 3 or 4 neutropenia (10%), leukopenia (6%), and thrombocytopenia (4.7%) were reported in patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial.
Immune-mediated hematologic toxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), and immune thrombocytopenic purpura; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Grade 3 or 4 hypocalcemia (3.9% or less), hyponatremia (2.9% to 6%), hypokalemia (1.5% to 2.3%), and hypophosphatemia (2.4% to 4.1%) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials.
Grade 3 or 4 hypermagnesemia (2.4% or less), hyperkalemia (4.2% or less), hypernatremia (1% or less), and hypercalcemia (1.2% to 2%) occurred in patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials.
Infection including upper respiratory tract infection (22% or less; grade 3 or 4, 1.1% or less), pneumonia (11% or less; grade 3 or 4, 5% or less), skin infection (11% or less; grade 3 or 4, 4.5% or less), and urinary tract infection including cystitis and urosepsis (13% or less; grade 3 or 4, 2.2% or less) occurred in patients who received cemiplimab as monotherapy in clinical trials. Fatal infection was reported in 2.2% of patients with advanced cutaneous squamous cell carcinoma who received single-agent cemiplimab (n = 358) in a clinical trial. Additionally, fatal pneumonia occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. The term upper respiratory tract infection included pharyngitis, laryngitis, nasopharyngitis, rhinitis, sinusitis, and influenza-like illness/influenza.
Hypertension including hypertensive crisis (17% or less; grade 3 or 4, 9% or less) occurred in 17% (grade 3 or 4, 9% or less) of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial.
Anti-cemiplimab antibody formation occurred in 2% of patients who received cemiplimab during a treatment period ranging from 8 to 19 months in 5 clinical trials. There was no evidence of altered pharmacokinetic parameters in patients who developed anti-cemiplimab antibodies.
Headache including migraine (13% or less; grade 3 or 4, 1.4%) and dizziness including vertigo (12% or less; grade 3 or 4, 0.3% or less) occurred in patients who received cemiplimab as monotherapy in clinical trials. Peripheral neuropathy occurred in 11% of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) and 23% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy in 2 clinical trials. The term peripheral neuropathy included paresthesias, dysesthesia, hypoesthesia, burning sensation, neuralgia, polyneuropathy, and toxic neuropathy.
Prolonged bleeding time including grade 3 or 4 increased INR occurred in 2.9% of patients with advanced cutaneous squamous cell carcinoma who received single-agent cemiplimab (n = 358) in a clinical trial. Additionally, grade 3 or 4 prolonged activated partial thromboplastin time occurred in 1.9% of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial.
Immune-mediated pancreatitis including increased serum amylase (hyperamylasemia) and lipase levels occurred in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or other PD-1/PD-L1 blocking antibodies; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Insomnia occurred in 11% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial.
Weight loss occurred in 11% (grade 3 or 4, 1.3%) of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial.
Grade 3 or 4 hypoalbuminemia occurred in 1% to 1.8% of patients who received cemiplimab as monotherapy or in combination with platinum chemotherapy in clinical trials.
Immune-mediated hypophysitis was reported in 0.5% (grade 3, 0.2%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with hormone replacement/endocrine therapy or systemic corticosteroids may be necessary.
Immune-mediated hypothyroidism occurred in 7% (grade 3, less than 0.1%) of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Increased blood thyroid stimulating hormone level was also reported. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with hormone replacement/endocrine therapy or systemic corticosteroids may be necessary.
Immune-mediated thyroiditis occurred in 0.6% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281). Thyroiditis can present with or without endocrinopathy. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with hormone replacement/endocrine therapy or systemic corticosteroids may be necessary.
Immune-mediated hypoparathyroidism was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or with other PD-1/PD-L1 blocking antibodies. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with hormone replacement/endocrine therapy or systemic corticosteroids may be necessary.
Other immune-mediated toxicity that was reported in less than 1% of patients who received cemiplimab as a single agent in a pooled safety analysis (n = 1,281) or that occurred with the use of other PD-1/PD-L1 blocking antibodies included systemic inflammatory response syndrome, sarcoidosis, and solid organ transplant rejection and other transplant rejection including corneal graft rejection; cases may be severe or fatal. Hold or permanently discontinue cemiplimab depending on toxicity severity; treatment with systemic corticosteroids or other systemic immunosuppressants may be necessary.
Fatal mesenteric artery thrombosis/mesenteric thrombosis occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. Ischemic stroke resulting in permanent therapy discontinuation occurred in 2 or more patients with locally advanced or metastatic NSCLC who received single-agent cemiplimab (n = 355) in a randomized trial.
Bleeding occurred in 18% (grade 3 or 4, 0.7%) of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. Fatal bleeding occurred in 0.3% of patients with locally advanced or metastatic non-small cell lung cancer who received cemiplimab in combination with platinum-based chemotherapy (n = 312) in a randomized trial. The term bleeding included tumor hemorrhage, hematuria, epistaxis, ocular hemorrhage, hemoptysis, intracranial bleeding, hemorrhagic diathesis, postmenopausal hemorrhage, rectal/GI bleeding, skin or wound hemorrhage, skin neoplasm bleeding, ulcer hemorrhage, and vaginal bleeding.
Edema occurred in 10% (grade 3 or 4, 0.7%) of patients with advanced basal cell carcinoma who received single-agent cemiplimab (n = 138) in a clinical trial. The term edema included peripheral edema, peripheral swelling, and face swelling.
Immune-mediated reactions, which may be severe or fatal, can occur in patients treated with drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), thus removing inhibition of the immune response, such as cemiplimab. These immune-mediated reactions can occur in any organ system or tissue and can also affect more than one body system simultaneously. Although usually occurring during treatment with PD-1/PD-L1 inhibitors, immune-mediated reactions can occur at any time after starting therapy including after discontinuation of therapy. Because early identification and management is critical to safe usage of PD-1/PD-L1 inhibitors, closely monitor patients for signs and symptoms that may be clinical manifestations of underlying immune-mediated reactions. Initiate an appropriate workup to exclude alternative etiologies including infection in cases of suspected immune-mediated reaction. Begin medical management promptly, including specialty consultation as appropriate. An interruption or discontinuation of cemiplimab therapy may be necessary, depending on the severity of the reaction. In general, if an interruption or discontinuation of therapy is necessary, administer systemic corticosteroids (1 to 2 mg/kg per day of prednisone or equivalent); upon improvement to grade 1 or less, begin a steroid taper over at least 1 month. Consider additional systemic immunosuppression in patients whose symptoms are not controlled with corticosteroid therapy.
Immune-mediated pneumonitis has been reported with cemiplimab therapy; some cases were fatal. The incidence of pneumonitis with other PD-1/PD-L1 inhibitors is higher in patients who have received prior thoracic radiation therapy. Monitor patients for signs and symptoms of pneumonitis (e.g., new or worsening cough, chest pain, shortness of breath). If confirmed, cemiplimab therapy may need to be interrupted or discontinued; treatment with systemic corticosteroids may be necessary.
Immune-mediated colitis has been reported with cemiplimab therapy. Additionally, cytomegalovirus (CMV) viral infection/reactivation has been reported in patients with steroid-refractory immune-mediated colitis. Use cemiplimab with caution in patients with pre-existing inflammatory bowel disease such as ulcerative colitis or Crohn's disease. Monitor patients for symptoms of colitis (e.g., diarrhea, severe abdominal pain). Cemiplimab therapy may need to be interrupted or discontinued depending on severity; treatment with systemic corticosteroids may be necessary. In patients with steroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
Immune-mediated hepatitis has been reported with cemiplimab therapy. Monitor hepatic function at baseline and periodically during treatment. Cemiplimab therapy may need to be interrupted or discontinued depending on the severity of hepatitis and if there is tumor involvement of the liver; treatment with systemic corticosteroids may also be necessary.
Use cemiplimab with caution in patients who have previously had an organ transplant or who have autoimmune disease such as systemic lupus erythematosus (SLE). Immune-mediated organ transplant rejection has been reported with PD-1/PD-L1 inhibitor therapy.
Primary or secondary adrenal insufficiency and immune-mediated hypophysitis can occur in patients treated with cemiplimab. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects; hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement therapy for grade 2 or higher adrenal insufficiency and for hypophysitis as clinically indicated. Cemiplimab therapy may need to be interrupted or discontinued depending on severity; treatment with systemic corticosteroids may also be necessary.
Cemiplimab can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy; hypothyroidism can follow hyperthyroidism. Evaluate thyroid function at baseline and monitor periodically during treatment. Begin hormone replacement for hypothyroidism or medical management of hyperthyroidism as clinically indicated. Cemiplimab therapy may need to be interrupted or discontinued depending on severity; treatment with systemic corticosteroids may also be necessary.
Type 1 diabetes mellitus, which can present with diabetic ketoacidosis, has been reported with cemiplimab therapy. Monitor patients for hyperglycemia and other signs and symptoms of diabetes. Withhold cemiplimab therapy for cases of severe hyperglycemia until blood sugar control is achieved; administer insulin as clinically indicated.
Immune-mediated nephritis has been reported with cemiplimab therapy; renal failure may occur. Monitor renal function at baseline and periodically during treatment. Cemiplimab therapy may need to be interrupted or discontinued depending on the severity of renal impairment; treatment with systemic corticosteroids may also be necessary.
Immune-mediated serious rash, including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) has occurred in patients treated with PD-1/PD-L1 inhibitors. Monitor patients for suspected severe skin reactions and exclude other causes. Topical emollients and/or topical corticosteroids may be adequate to treat mild-to-moderate non-exfoliative rashes. Cemiplimab therapy may need to be interrupted or discontinued depending on the severity of rash; treatment with systemic corticosteroids may also be necessary.
Severe infusion-related reactions have occurred with cemiplimab. Monitor patients for signs and symptoms of infusion reactions including fever, chills, wheezing, pruritus, rash, and flushing. Interrupt or slow the rate of infusion for mild or moderate infusion related reactions (grade 1 or 2); stop the infusion and permanently discontinue cemiplimab for severe or life-threatening infusion-related reactions (grade 3 or 4).
Immune-mediated neurotoxicity has been reported with cemiplimab or other PD-1/PD-L1 inhibitors. Use cemiplimab with caution in patients who have a history of neurological disease such as myasthenia gravis or Guillain-Barre syndrome. Cemiplimab may need to be interrupted or discontinued depending on the severity of the neurotoxicity; treatment with systemic corticosteroids may also be necessary.
Fatal and other serious complications including hyperacute, acute, and chronic graft-versus-host-disease, sinusoidal obstruction syndrome (SOS) previously termed veno-occlusive disease (VOD) after reduced intensity conditioning, and a steroid-requiring febrile syndrome (without an identified infectious cause) have been reported in patients who receive an allogeneic stem cell transplant (SCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Therefore, perform a risk/benefit analysis prior to starting treatment with a PD-1/PD-L1 blocking antibody, such as cemiplimab, in patients who may receive or who have a history of undergoing an allogeneic SCT. Monitor patients closely for evidence of transplant-related complications and intervene promptly. Complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic SCT.
Based on its mechanism of action, cemiplimab may cause fetal harm if administered during pregnancy by increasing the risk of immune-mediated rejection of the developing fetus; increasing the risk of developing immune-related disorders or altering the normal immune response in the fetus is also possible. Human IgG4 immunoglobulins are known to cross the placenta; therefore, there may be drug exposure to the developing fetus. If cemiplimab is used during pregnancy or if a woman becomes pregnant while receiving it, the patient should be apprised of the potential hazard to the fetus. The programmed death receptor-1 (PD-1)/PD-1 ligand (PDL-1) pathway helps to preserve pregnancy by maintaining maternal tolerance to the fetus. Inhibiting PD-1/PDL-1 binding and signaling led to an increase in fetal loss in murine models. Potential risks for blocking the PD-1/PDL-1 pathway include an increased incidence of abortion or stillbirths.
Counsel patients about the reproductive risk and contraception requirements during cemiplimab therapy. Pregnancy testing should be performed prior to starting cemiplimab in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 4 months after cemiplimab therapy. Women who become pregnant while receiving cemiplimab should be apprised of the potential hazard to the fetus.
It is not known if cemiplimab is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because of a potential for adverse reactions in nursing infants from cemiplimab, women should discontinue breast-feeding during cemiplimab therapy and for at least 4 months after the last dose.
For the treatment of squamous cell skin carcinoma:
-for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation:
Intravenous dosage:
Adults: 350 mg IV repeated every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. The objective response rates (ORR) were 50.8% (median follow-up, 18.5 months) and 42.9% (median follow-up, 17.3 months) in patients with metastatic cutaneous squamous cell carcinoma (CSCC) who received weight-based (group 1, n = 59; 3 mg/kg IV every 2 weeks) and flat-dose (group 3, n = 56; 350 mg IV every 3 weeks) cemiplimab, respectively, in a nonrandomized, multicohort, phase 2 study (Study 1540); the complete response (CR) rates were 20.3% and 16.1%, respectively. At a median follow-up of 15.5 months, the ORR was 44.9% (CR rate, 12.8%) in patients with locally advanced CSCC who received cemiplimab 3 mg/kg IV every 2 weeks (group 2, n = 78) in this trial. The median duration of response was not reached in any cohort. The estimated median progression-free survival time was 18.4 months and the median overall survival time had not been reached in patients with advanced CSCC who received cemiplimab (n = 193). Most patients in this trial had a primary CSCC site at the head or neck (67.9%) and had not received prior systemic therapy (66.3%).
For the treatment of basal cell carcinoma (BCC):
-for the treatment of locally advanced or metastatic BCC in patients who have previously received a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate:
Intravenous dosage:
Adults: 350 mg IV repeated every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. At a median follow-up time of 8.4 months, the confirmed objective response rate (ORR) was 24% (complete response (CR) rate, 2%) in patients with metastatic BCC (n = 54) who received cemiplimab in a nonrandomized, phase 2 study (Study 1620). At a median follow-up of 15 months, the ORR (per an independent central review) was 31% (CR, 6%) in patients with locally advanced BCC (n = 84) who received cemiplimab in Study 1620. At follow-up, the median durations of response were 16.7 (range, 4.8 to more than 25.8) months in patients with metastatic BCC and not reached (range, 2 to 21 months) in patients with locally advanced BCC. In patients with locally advanced BCC, the estimated median progression-free survival time was 19 months and the median overall survival time had not been reached.
For the treatment of non-small cell lung cancer (NSCLC):
-for the first-line treatment of locally advanced or metastatic NSCLC in patients whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS], 50% or more) with no EGFR, ALK or ROS1 aberrations. Patients with locally advanced NSCLC should not be candidates for surgical resection or definitive chemoradiation:
NOTE: Patients should be selected based on PD-L1 expression on tumor cells. Information on FDA-approved tests for the detection of PD-L1 expression is available at www.fda.gov/CompanionDiagnostics.
Intravenous dosage:
Adults: 350 mg IV every 3 weeks until disease progression or unacceptable toxicity. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. First-line treatment with cemiplimab significantly improved median overall survival (22.1 months vs. 14.3 months) and progression-free survival (6.2 months vs. 5.6 months) compared with investigator's choice of chemotherapy in a multicenter, randomized, open-label clinical trial (Study 1624) in patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC who had tumors with high PD-L1 expression and no EGFR, ALK, or ROS1 aberrations. The overall response rate was 37% for a median duration of 21 months in patients treated with cemiplimab compared with 21% for a median duration of 6 months in those who received chemotherapy, with a complete response in 3% vs. 1% of patients, respectively.
-for the first-line treatment of locally advanced or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations, in combination with carboplatin and paclitaxel. Patients with locally advanced NSCLC should not be candidates for surgical resection or definitive chemoradiation:
Intravenous dosage:
Adults: 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with paclitaxel (200 mg/m2 IV) and carboplatin (AUC 5 or 6 IV) every 3 weeks for 4 cycles. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. In a randomized, multicenter, double-blind clinical trial (EMPOWER-Lung 3), treatment with cemiplimab in combination with platinum-based chemotherapy improved median overall survival (21.9 months vs. 13 months) and median progression-free survival (PFS) (8.2 months vs. 5 months) compared with placebo plus chemotherapy in patients with locally advanced or metastatic NSCLC without EGFR, ALK, or ROS1 aberrations. The overall response rate was also significantly improved in the cemiplimab arm (43% vs. 23%; complete response, 2.6% vs. 0%) for a median duration of 15.6 months and 7.3 months, respectively.
-for the first-line treatment of locally advanced or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations, in combination with cisplatin and paclitaxel. Patients with locally advanced NSCLC should not be candidates for surgical resection or definitive chemoradiation:
Intravenous dosage:
Adults: 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with cisplatin (75 mg/m2 IV) and paclitaxel (200 mg/m2 IV) every 3 weeks for 4 cycles. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. In a randomized, multicenter, double-blind clinical trial (EMPOWER-Lung 3), treatment with cemiplimab in combination with platinum-based chemotherapy improved median overall survival (21.9 months vs. 13 months) and median progression-free survival (PFS) (8.2 months vs. 5 months) compared with placebo plus chemotherapy in patients with locally advanced or metastatic NSCLC without EGFR, ALK, or ROS1 aberrations. The overall response rate was also significantly improved in the cemiplimab arm (43% vs. 23%; complete response, 2.6% vs. 0%) for a median duration of 15.6 months and 7.3 months, respectively.
-for the first-line treatment of locally advanced or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations, in combination with carboplatin and pemetrexed. Patients with locally advanced NSCLC should not be candidates for surgical resection or definitive chemoradiation:
Intravenous dosage:
Adults: 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with carboplatin (AUC 5 or 6 IV) and pemetrexed (500 mg/m2 IV) every 3 weeks for 4 cycles; maintenance pemetrexed should continue until disease progression or unacceptable toxicity. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. In a randomized, multicenter, double-blind clinical trial (EMPOWER-Lung 3), treatment with cemiplimab in combination with platinum-based chemotherapy improved median overall survival (21.9 months vs. 13 months) and median progression-free survival (PFS) (8.2 months vs. 5 months) compared with placebo plus chemotherapy in patients with locally advanced or metastatic NSCLC without EGFR, ALK, or ROS1 aberrations. The overall response rate was also significantly improved in the cemiplimab arm (43% vs. 23%; complete response, 2.6% vs. 0%) for a median duration of 15.6 months and 7.3 months, respectively.
-for the first-line treatment of locally advanced or metastatic NSCLC with no EGFR, ALK or ROS1 aberrations, in combination with cisplatin and pemetrexed. Patients with locally advanced NSCLC should not be candidates for surgical resection or definitive chemoradiation:
Intravenous dosage:
Adults: 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Administer in combination with cisplatin (75 mg/m2 IV) and pemetrexed (500 mg/m2 IV) every 3 weeks for 4 cycles; maintenance pemetrexed should continue until disease progression or unacceptable toxicity. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. In a randomized, multicenter, double-blind clinical trial (EMPOWER-Lung 3), treatment with cemiplimab in combination with platinum-based chemotherapy improved median overall survival (21.9 months vs. 13 months) and median progression-free survival (PFS) (8.2 months vs. 5 months) compared with placebo plus chemotherapy in patients with locally advanced or metastatic NSCLC without EGFR, ALK, or ROS1 aberrations. The overall response rate was also significantly improved in the cemiplimab arm (43% vs. 23%; complete response, 2.6% vs. 0%) for a median duration of 15.6 months and 7.3 months, respectively.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Immune-Mediated Reactions
NOTE: Corticosteroid therapy consists of prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less. Consider starting other systemic immunosuppressants if toxicity is not controlled by corticosteroids. Permanently discontinue cemiplimab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids.
Colitis
Grade 2 or 3 toxicity: Hold cemiplimab and administer corticosteroids. Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper.
Grade 4 toxicity: Permanently discontinue cemiplimab and administer corticosteroids.
Endocrinopathies (including Type 1 diabetes, Hypophysitis, Hypothyroidism, Hyperthyroidism, and Adrenal Insufficiency)
Grade 3 or 4 toxicity: Hold cemiplimab until the patient is clinically stable; administer appropriate treatment (e.g., hormone replacement therapy, corticosteroids, insulin). Permanently discontinue cemiplimab for severe toxicity.
Exfoliative Skin Reactions
Suspected Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS): Hold cemiplimab and administer corticosteroids as applicable.
Confirmed SJS, TEN, or DRESS: Permanently discontinue cemiplimab and administer corticosteroids.
Infusion-Related Reactions
Grade 1 or 2 toxicity: Hold cemiplimab or slow the infusion rate.
Grade 3 or 4 toxicity: Permanently discontinue cemiplimab.
Myocarditis
Grade 2, 3, or 4 toxicity: Permanently discontinue cemiplimab and administer corticosteroids.
Neurologic Toxicity
Grade 2 toxicity: Hold cemiplimab and administer corticosteroids. Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper.
Grade 3 or 4 toxicity: Permanently discontinue cemiplimab and administer corticosteroids.
Pneumonitis
Grade 2 toxicity: Hold cemiplimab and administer corticosteroids. Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper.
Grade 3 or 4 toxicity: Permanently discontinue cemiplimab and administer corticosteroids.
Other Immune-Mediated Adverse Reactions
Grade 3 toxicity: Hold cemiplimab and administer corticosteroids. Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper.
Recurrent grade 3 toxicity that requires treatment with systemic immunosuppressants: Permanently discontinue cemiplimab.
Grade 4 toxicity: Permanently discontinue cemiplimab and administer corticosteroids.
Maximum Dosage Limits:
-Adults
350 mg IV every 3 weeks.
-Geriatric
350 mg IV every 3 weeks.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Treatment-Related Immune-Mediated Hepatitis
No Tumor Involvement of the Liver
AST or ALT level of more than 3 to 8 times the ULN or a total bilirubin level of more than 1.5 to 3 times the ULN: Hold cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue cemiplimab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids.
AST or ALT level more than 8 times the ULN or a total bilirubin level more than 3-times the ULN: Permanently discontinue cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).
Tumor Involvement of the Liver
Baseline AST or ALT level at the ULN or less: Hold or permanently discontinue cemiplimab based on recommendations for hepatitis with no tumor involvement of the liver.
Baseline AST or ALT level of more than 1 to 3 times the ULN
AST or ALT level of more than 5 to 10 times the ULN: Hold cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue cemiplimab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids.
Baseline AST or ALT level of more than 3 to 5 times the ULN
AST or ALT level of more than 8 to 10 times the ULN: Hold cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue cemiplimab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids.
Any Baseline AST or ALT level
AST or ALT level more than 10 times the ULN or a total bilirubin level to more than 3 times the ULN: Permanently discontinue cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).
Patients with Renal Impairment Dosing
Treatment-Related Immune-Mediated Nephritis with Renal Dysfunction
Grade 2 or 3 increased serum creatinine (SCr) level: Hold cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue cemiplimab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids.
Grade 4 increased SCr level: Permanently discontinue cemiplimab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).
*non-FDA-approved indication
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Cemiplimab is a recombinant human immunoglobulin G4 monoclonal antibody that binds to the programmed death receptor-1 (PD-1) found on T-cells and blocks the interaction of PD ligand-1 (PD-L1) and PD-L2 with PD-1 on the tumor cell. Blocking the PD-1/PD-L1 pathway improves the anti-tumor immune response by reducing immunosuppressive signals between immune cells and tumor cells and causes inhibition of T-cell proliferation and cytokine production. In mice models, cemiplimab inhibited PD-1 activity resulting in decreased tumor growth.
Cemiplimab is administered intravenously. It has a steady-state volume of distribution of 5.9 L (coefficient of variation (CV), 29%), steady-state clearance of 0.22 L/day (CV, 44%), and elimination half-life of 22 days (CV, 42%).
-Route-Specific Pharmacokinetics
Intravenous Route
The median steady-state concentrations ranged between a Cmin of 59 mcg/mL (CV, 47%) and a Cmax of 171 mcg/mL (CV, 27%) in patients who received cemiplimab 350 mg IV every 3 weeks. The median steady-state cemiplimab exposure was reached after 4 months of treatment. The pharmacokinetics of cemiplimab was linear and increased proportionally in the dose range of 1 to 10 mg/kg IV every 2 weeks. In patients with cutaneous squamous cell carcinoma, the steady-state exposure is comparable with cemiplimab 350 mg IV every 3 weeks and 3 mg/kg IV every 2 weeks dosing.
-Special Populations
Hepatic Impairment
Hepatic function (total bilirubin level greater than 1 to 3 times the ULN) has no clinically significant impact on the exposure of cemiplimab. Cemiplimab has not been evaluated in patients with severe hepatic impairment.
Renal Impairment
Renal function (creatinine clearance, 21 mL/min or higher) has no clinically significant impact on the exposure of cemiplimab.
Geriatric
Age (range, 27 to 96 years) has no clinically significant impact on the exposure of cemiplimab.
Gender Differences
Gender has no clinically significant impact on the exposure of cemiplimab.
Ethnic Differences
Race (Asian, Black, White) has no clinically significant impact on the exposure of cemiplimab.
Obesity
Weight (range, 31 to 172 kg) has no clinically significant impact on the exposure of cemiplimab.
Other
Tumor Type
The type of cancer has no clinically significant impact on the exposure of cemiplimab.
Hypoalbuminemia
Albumin level (range, 20 to 93 g/L) has no clinically significant impact on the exposure of cemiplimab.