Cemiplimab – Uses, Dosage, Side Effects, Interaction

Cemiplimab is a programmed death receptor-1 blocking antibody used to treat cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer.

Cemiplimab is a fully human monoclonal antibody that works against programmed death receptor-1 (PD-1), which is a negative regulator of T-cell function. By blocking PD-1, cemiplimab works to enhance T cell-mediated antitumor responses. Cemiplimab is a monoclonal antibody medication for the treatment of squamous cell skin cancer. Cemiplimab belongs to a class of drugs that binds to the programmed death receptor-1 (PD-1), blocking the PD-1/PD-L1 pathway.

Cemiplimab was first approved by the FDA on September 28, 2018, as the first FDA-approved treatment for advanced cutaneous squamous cell carcinoma (CSCC). It was later approved to be used in basal cell carcinoma and non-small non-small cell lung cancer.[rx] Cemiplimab was also approved by the European Commission on June 28, 2019.[rx] In October 2022, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended cemiplimab be granted marketing authorization for the treatment of cervical cancer.[rx]

Mechanism of action

T cells mediate antitumor activity following activation by antigen receptor signaling and CD28 costimulatory signaling.[rx,rx] T cell proliferation and activation are regulated by a number of T cell immune regulatory checkpoints, including programmed death-1 (PD-1).[rx] PD-1 is an inhibitory co-receptor that is predominantly expressed on the surface of T cells to block T cell activation.[rx,rx,rx] Its ligands, PD-L1, and PD-L2, bind to PD-1 to activate downstream signaling cascades that ultimately result in the inhibition of T cell function such as T cell proliferation, cytokine production, and cytotoxicity.[rx,rx] PD-1 receptor signaling pathway serves to maintain tolerance and regulate any ineffective or harmful immune responses; however, PD-1 signaling can also attenuate immune responses in cases where such protection is needed, such as autoimmune disorders and malignancy.[rx]

PD-L1 and PD-L2 are expressed on antigen-presenting cells (APCs) as well as on some types of tumor cells 2,8 as part of an adaptive immune response by tumors.[rx,rx] PD-1 is also upregulated in some cancers, impeding T cell-mediated antitumor activity.6 Cemiplimab is a human PD-1-blocking antibody that binds to PD-1 and blocks its interaction with its ligands. By disinhibiting PD-1-mediated suppression of T cell activity, cemiplimab works to potentiate T cell cytotoxicity against tumors.[rx]

Indications

  • Locally advanced or metastatic cutaneous squamous cell carcinoma (mCSCC) in patients who are not candidates for curative surgery or curative radiation.
  • Locally advanced basal cell carcinoma (laBCC) in previously treated patients with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.
  • Metastatic basal cell carcinoma (mBCC) in patients who were previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for mBCC may be contingent upon verification and description of clinical benefit.[rx,rx]
  • Locally advanced non-small cell lung cancer (NSCLC) in combination with platinum‐based chemotherapy for the first‐line treatment of adults with no EGFR, ALK, or ROS1 aberrations, who are not candidates for surgical resection or definitive chemoradiation. It is also indicated to treat metastatic NSCLC in combination with platinum‐based chemotherapy as first-line treatment in adults.[rx]
  • Locally advanced or metastatic NSCLC as monotherapy for the first-line treatment of adults whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Patients with locally advanced NSCLC must not be candidates for surgical resection or definitive chemoradiation.[rx]
  • Locally Advanced Basal Cell Carcinoma
  • Locally Advanced Cutaneous Squamous Cell Carcinoma
  • Locally Advanced Non-Small Cell Lung Cancer
  • Metastatic Non-Small Cell Lung Cancer
  • Metastatic cutaneous squamous cell carcinoma
  • Metastatic Basal cell carcinoma

Use in Cancer

Cemiplimab-rwlc is approved to treat:

  • Basal cell carcinoma (a type of skin cancer). It is used in patients whose cancer cannot be removed by surgery or has spread after treatment with hedgehog pathway inhibitor therapy or if hedgehog pathway inhibitor therapy cannot be used.
  • Cutaneous squamous cell carcinoma (a type of skin cancer) has spread or cannot be treated with surgery or radiation therapy.
  • Non-small cell lung cancer. It is used in adults whose cancer has not spread outside the chest and cannot be treated with surgery or chemotherapy and radiation therapy or has spread to other parts of the body. It is used:
    • Alone is the first treatment when cancer has the PD-L1 protein but does not have a mutation in the EGFR, ALK, or ROS1 gene.
    • Platinum chemotherapy is the first treatment when cancer does not have a mutation in the EGFR, ALK, or ROS1 gene.

The use for metastatic BCC is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that cemiplimab-rwlc provides a clinical benefit in these patients.

Cemiplimab-rwlc is also being studied in the treatment of other types of cancer.

Contraindications

  • myasthenia gravis, a skeletal muscle disorder
  • a type of inflammation of the lung called interstitial pneumonitis
  • inflammation of the large intestine
  • liver inflammation resulting from an abnormal immune response
  • kidney inflammation
  • pregnancy
  • a patient who is producing milk and breastfeeding

Dosage

Strengths: rwlc 350 mg/7 mL

Squamous Cell Carcinoma

  • 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity

Basal Cell Carcinoma

  • 350 mg IV over 30 minutes every 3 weeks until disease progression or unacceptable toxicity
  • For locally advanced basal cell carcinoma (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate
  • For metastatic BCC (mBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate

Dose Adjustments

No dose reduction for this drug is recommended:

  • In general, withhold therapy for severe (Grade 3) immune-mediated adverse reactions.
  • Permanently discontinue therapy for life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressives, or inability to reduce corticosteroid to 10 mg or less prednisone equivalent per day within 12 weeks of initiation.

PNEUMONITIS:

  • Grade 2: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • Grade 3 or 4: Permanently discontinue therapy.

COLITIS:

  • Grade 2 or 3: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation
  • Grade 4: Permanently discontinue therapy.

HEPATITIS (WITH NO TUMOR INVOLVEMENT OF THE LIVER):

  • If AST or ALT increases to more than 3 and up to 8 times the upper limit of normal (ULN) OR total bilirubin increases more than 1.5 and up to 3 x ULN: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • If AST or ALT increases to more than 8 x ULN OR total bilirubin increases to more than 3 x ULN: Permanently discontinue therapy.

HEPATITIS (WITH TUMOR INVOLVEMENT OF THE LIVER):

  • Baseline AST or ALT is more than 1 and up to 3 x ULN and increases to more than 5 and up to 10 x ULN OR baseline AST or ALT is more than 3 and up to 5 x ULN and increases to more than 8 and up to 10 times ULN: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • AST or ALT increases to more than 10 x ULN OR total bilirubin increases to more than 3 x ULN: Permanently discontinue therapy.

ENDOCRINOPATHIES:

  • Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity.

NEPHRITIS WITH RENAL DYSFUNCTION:

  • Grade 2 or 3 increased blood creatinine: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • Grade 4 increased blood creatinine: Permanently discontinue therapy.

EXFOLIATIVE DERMATOLOGIC CONDITIONS:

  • Suspected SJS, TEN, or DRESS: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • Confirmed SJS, TEN, or DRESS: Permanently discontinue therapy.
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MYOCARDITIS:

  • Grade 2, 3, or 4: Permanently discontinue therapy.

NEUROLOGICAL TOXICITIES:

  • Grade 2: Withhold therapy; resume if resolved to Grade 1 or less after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiation.
  • Grade 3 or 4: Permanently discontinue therapy.

INFUSION-RELATED REACTIONS:

  • Grade 1 or 2: Interrupt or slow the rate of infusion.
  • Grade 3 or 4: Permanently discontinue therapy.

Side Effects

The Most Common

  • constipation
  • cough; irregular heartbeat; chest pain; or shortness of breath
  • diarrhea; stools that are black, tarry, sticky, or have blood or mucus; or abdominal pain or tenderness
  • yellow eyes or skin; severe nausea or vomiting; dark urine; loss of appetite; unusual bleeding or bruising; or pain or discomfort in right upper stomach area
  • rash; blistering skin; itching; swollen lymph nodes; or painful sores or ulcers in mouth or nose, throat, or genital area
  • decreased urine amount; swelling in your ankles; blood in urine; loss of appetite
  • headache, feeling more hungry or thirsty than usual; increased sweating; extreme tiredness; frequent urination; nausea; vomiting; or weight changes
  • double vision, blurry vision, eye sensitivity to light, eye pain, or changes in vision
  • feeling cold; deepening of voice or hoarseness; hair loss; irritability; dizziness or fainting; fast heartbeat; forgetfulness; or changes in sexual desire
  • confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, or tingling or numbness of arms or legs
  • muscle pain or weakness or muscle cramps

More Common

  • new or worsening cough, shortness of breath;
  • chest pain, fast or irregular heartbeats;
  • swollen glands;
  • a seizure;
  • severe headache, confusion, hallucinations, eye pain or redness, vision problems (your eyes may be more sensitive to light);
  • severe muscle pain or weakness, neck stiffness;
  • severe stomach pain, nausea, vomiting, diarrhea, bloody or tarry stools;
  • unusual bruising;
  • transplant rejection–mouth sores, stomach pain, feeling sick or uneasy, rash, pain or swelling near your transplanted organ;
  • kidney problems–swelling in your ankles, blood in your urine, little or no urination;
  • liver problems–right-sided upper stomach pain, loss of appetite, drowsiness, easy bruising or bleeding, dark urine, jaundice (yellowing of the skin or eyes);
  • signs of a hormonal disorder–frequent or unusual headaches, dizziness, feeling very tired, mood or behavior changes, hoarse or deepened voice, increased hunger or thirst, increased urination, constipation, hair loss, sweating, feeling cold, weight gain, or weight loss.
  • tiredness;
  • muscle or bone pain;
  • rash, itching; or
  • nausea, diarrhea.

Rare

  • slow or fast heartbeat
  • sneezing
  • sore throat
  • stiff neck or back
  • thickening of bronchial secretions
  • trouble breathing
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • Blistering, peeling, or loosening of the skin
  • difficulty in moving
  • joint or muscle pain
  • muscle aches, cramps, or stiffness
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • sores, ulcers, or white spots in the mouth or on the lips
  • swollen glands
  • swollen joints

Drug Interaction

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Pregnancy and Lactation

US FDA pregnancy category Not Assigned

Pregnancy

Based on its mechanism of action, this drug can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD1/PD-L1 pathway can lead to an increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, this drug has the potential to be transmitted from the mother to the developing fetus.

Lactation

Because of the potential for serious adverse reactions in breastfed children, women should not breastfeed during therapy and for at least 4 months after the last dose. Because this drug is a large protein molecule, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant’s GI tract. The manufacturer recommends that breastfeeding be discontinued during therapy and for 4 months after.

How should this medicine be used?

Cemiplimab-rwlc injection comes as a solution (liquid) to inject intravenously (into a vein) over 30 minutes by a doctor or nurse in a medical facility or infusion center. It is usually given every 3 weeks.

Your doctor may need to slow down your infusion or interrupt or stop your treatment if you experience certain side effects. Tell your doctor immediately if you experience any of the following symptoms during or after your infusion: chills or shaking fever, itching, rash, feeling faint, flushing, nausea, back or neck pain, shortness of breath, dizziness, wheezing, or face swelling.

Your doctor may delay, or stop your treatment with cemiplimab-rwlc injection depending on your response to the medication and any side effects that you experience. Talk to your doctor about how you are feeling during and after your treatment.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with cemiplimab-rwic injection each time you receive a dose. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.

What special precautions should I follow?

Before receiving a cemiplimab-rwlc injection,

  • tell your doctor and pharmacist if you are allergic to cemiplimab-rwlc injection, any other medications, or any of the ingredients in cemiplimab-rwlc injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) or has ever had an organ transplant. Also, tell your doctor if you have or have ever had diabetes, Crohn’s disease (a condition in which the body attacks the lining of the digestive tract, causing pain, diarrhea, weight loss, and fever), ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum), lupus (a disease in which the body attacks many of its own organs), a nervous system disease such as myasthenia gravis (a disorder of the nervous system that causes muscle weakness), a lung disease or breathing problems, or thyroid, liver or kidney disease.
  • tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while you are receiving the cemiplimab-rwlc injection. You will need to have a pregnancy test before you begin receiving this medication. Use effective birth control during your treatment with cemiplimab-rwlc injection and for 4 months after your final dose. If you become pregnant while receiving a cemiplimab-rwlc injection, call your doctor. The cemiplimab-rwlc injection may harm the fetus.
  • tell your doctor if you are breastfeeding. Your doctor will tell you not to breastfeed during your treatment with cemiplimab-rwlc injection and for 4 months after your final dose.

References