Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
cemiplimab
Cemiplimab is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor on T-cells, blocking interaction with PD-L1 and PD-L2 and countering PD-1 mediated immune response inhibition.
Cemiplimab exhibits linear and dose proportional pharmacokinetics in the dose range of 1 to 10 mg/kg q2 weekly and 350 mg q3 weekly. Steady state exposure is reached after approximately 4 months of treatment.
Cemiplimab is metabolized by proteolysis without formation of active metabolites.
| Half-life |
22 days (at steady state) |
- Cutaneous squamous cell carcinoma (CSCC)
- Basal cell carcinoma
- Non-small cell lung cancer
- Cervical cancer
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
Extravasation Potential: None
The following adverse effects include those reported in ≥ 5 patients from the pivotal phase II study in metastatic CSCC. It also includes severe or life-threatening adverse effects from other sources or post-marketing.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Myocarditis (<1%) | E D | |||
| Dermatological | Rash, pruritus (15%) (including SJS, TEN; may be severe) | E | |||
| Gastrointestinal | Anorexia, weight loss (14%) | E | |||
| Constipation (15%) | E | ||||
| Diarrhea (27%) (including colitis; may be severe) | E | ||||
| Mucositis (may be severe) | E | ||||
| Nausea, vomiting (17%) | E | ||||
| General | Fatigue (24%) | E | |||
| Hematological | Immune thrombocytopenic purpura (rare) | E D | |||
| Myelosuppression (9%) (including anemia; 2% severe) | E | ||||
| Hepatobiliary | ↑ LFTs (9%) (including hepatitis; may be severe) | E D | |||
| Hypersensitivity | Infusion related reaction (3%) | I | |||
| Immune | Immune-mediated reactions - solid organ transplant rejection (rare) | D L | |||
| Other - Sjogren's syndrome (rare) | E D | ||||
| Metabolic / Endocrine | Adrenal insufficiency (<1%) | E D | |||
| Diabetes mellitus (<1%) (new onset) | E D | ||||
| Hyperthyroidism (2%) (< 1% severe) | E D | ||||
| Hypophysitis (<1%) | E D | ||||
| Hypothyroidism (9%) | E D | ||||
| Nervous System | Headache (14%) | E | |||
| Meningitis (<1%) | E | ||||
| Myasthenia (rare) | E D | ||||
| Myositis (rare) | E D | ||||
| Neurotoxicity (<1%) | E D | ||||
| Renal | Nephritis (<1%) | E D | |||
| Respiratory | Cough (14%) | E | |||
| Pneumonitis (9%) (3% severe) | E D | ||||
| Vascular | Vasculitis (rare) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for cemiplimab include diarrhea, fatigue, nausea, vomiting, constipation, rash, pruritus, anorexia, weight loss, cough, and headache.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.
Presentation of immune-mediated reactions may be different compared to other anti-cancer agents and early diagnosis and appropriate management is critical.
Immune-mediated reactions, including pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, neuropathies and rash, have been reported and may be severe or fatal.
Immune-related pneumonitis, including fatal cases, has been reported. The median time to onset was 2 months and the median duration of pneumonitis was 1 month.
Immune-related diarrhea or colitis has been observed. The median time to onset was 4 months and the median duration was 2 months.
Severe or fatal cases of immune-related hepatitis have been observed in patients treated with cemiplimab. Two percent of patients experienced > Grade 3 immune-related hepatitis. The median time to onset was 3 months and the median duration of hepatitis was 2 months.
Immune-related endocrinopathies, including thyroid disorders, hypophysitis, adrenal insufficiency and type 1 diabetes mellitus, have occurred. Thyroid disorders can occur at any time during the treatment. For hypothyroidism, the median time to onset and duration were 4 months and 8 months, respectively. For hyperthyroidism, the median time to onset and duration were 2 months and 2 months, respectively. The median time to onset and duration for adrenal insufficiency were 12 months and 5 months, respectively.
Severe or fatal immune-related skin adverse reactions, including rash, erythema multiforme, pemphigoid, and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been observed. The median time to onset was 1 month and the median duration was 3 months.
Immune-related nephritis has been rarely reported with a median time to onset of 2 months and a median duration of nephritis of 1 month.
Immune-related nervous system disorders occurred rarely, including paraneoplastic encephalomyelitis, Guillain-Barre syndrome, encephalitis, chronic inflammatory demyelinating polyradiculoneuropathy and central nervous system inflammation.
Cases of severe or fatal immune-related adverse reactions have been reported in patients with prior treatment with idelalisib.
Cases of solid organ transplant rejection have been reported during postmarketing surveillance. Cemiplimab may increase the risk of organ rejection; consider the benefit versus the risk of treatment.
Graft-versus-host -disease has been reported in patients who received other PD-1/PD-L1 inhibits associated with allogeneic hematopoietic stem cell transplant.
Infusion-related reactions occurred in 7% of patients, including 1 patient with Grade 3 infusion-related reaction.
Refer to protocol by which patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Some treatment indications require a validated test to determine PD-L1 tumour status . Refer to the product monograph for details.
Premedication (prophylaxis for infusion reactions):
- Routine pre-medication is not recommended. No premedication was given for the first dose of cemiplimab during clinical trials.
- May consider premedication in patients who experienced a grade 1-2 infusion reaction (Migden et al). Refer to Management of Infusion-related Reactions table.
OR
(in patients with a low body weight at the discretion of the treating healthcare professional)
Intravenous: 3 mg/kg Every 2 weeks*
*Dosing based on NDFP funding criteria
Combination therapy
Various dosing and schedules are used depending on the indication. Refer to the product monograph or related regimen monographs for details.
Dose reductions are not recommended for cemiplimab. Doses may be delayed or discontinued based on toxicity.
Healthcare professionals should also consult the most recent cemiplimab product monograph for additional information.
Summary of Principles of Management of Immune-related Adverse Effects (irAEs):
- Immune-related adverse effects (irAEs) are different in their presentation, onset and duration compared to conventional chemotherapy. Patient and provider education is essential.
- Initial irAEs presentation can occur months after completion of treatment and affect multiple organs.
- Dose escalation or reduction is not recommended.
- If no other cause can be identified (such as infection), any new symptom should be considered immune-related and prompt treatment initiated.
- Organ-specific system-based toxicity management is recommended.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.
Management of Infusion-related Reactions:
| Grade | Management | Re-challenge* |
| 1 |
|
Consider premedication (at least 30 min prior to infusion) with:
|
|
2 |
|
Consider premedication (at least 30 min prior to infusion) with:
|
|
3 or 4 |
|
Permanently discontinue (do not re-challenge) |
*Based on Migden et al.
No formal studies in patients with hepatic impairment have been conducted.
Based on population pharmacokinetic analysis:
|
Hepatic Impairment |
Cemiplimab Dose |
|
Mild (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 x ULN and any AST) OR Moderate (bilirubin >1.5 to 3 x ULN and any AST) |
No dosage adjustment is required |
|
Severe (bilirubin >3 x ULN and any AST) |
No data |
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for management of immune-related hepatic toxicities.
No formal studies in patients with renal impairment have been conducted.
Based on population pharmacokinetic analysis:
| Creatinine Clearance (mL/min) | Cemiplimab Dose |
| > 15 | No dose adjustment |
| < 15 | No data |
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for management of immune-related renal toxicities.
No dose adjustment required. No overall differences in efficacy were observed between patients ≥ 65 years of age and younger patients. Trends towards a higher frequency of serious adverse events and discontinuations were observed in patients 65 years and older compared to younger patients.
Safety and efficacy in children have not been established.
- Undiluted solution should be clear to slightly opalescent, colourless to pale yellow; discard if cloudy, discoloured or contains extraneous particulate matter other than trace amounts of translucent-to-white particles.
- Dilute in 0.9% Normal Saline or 5% Dextrose to a final concentration between 1 to 20mg/mL. Mix by gentle inversion; do not shake.
- Infuse over 30 minutes using a sterile, 0.2 to 5 micron in-line or add-on filter.
- Do not co-administer with other drugs through the same infusion line.
- When administered in combination with chemotherapy agents, infuse the chemotherapy first, followed by cemiplimab on the same day. Use separate infusion bags and filters for each infusion.
- Store vials at 2-8 °C; do not freeze. Protect from light.
- Patients who have a hypersensitivity to this drug or any of its components
- Cemiplimab may cause serious immune-related reactions affecting multiple organ systems. Use with caution and monitor closely in patients with pre-existing conditions such as colitis, hepatic or renal impairment, respiratory or endocrine disorders, such as hypo or hyperthyroidism or diabetes mellitus.
- Patients experiencing fatigue should exercise caution when driving or operating machinery.
Other Drug Properties:
-
Carcinogenicity:
Unknown
-
Fetotoxicity:
Probable
-
Genotoxicity:
Unknown
-
Teratogenicity:
Unknown
Cemiplimab is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 4 months after the last dose.
Animal reproduction studies have not been conducted.
-
Excretion into breast milk:
Unknown
Breastfeeding is not recommended during treatment and for at least 4 months after the last dose.
-
Fertility effects:
Unknown
No clinical data on fertility are available; no effects on fertility or in the male and female reproductive organs were observed in animal studies.
No drug interaction studies have been conducted.
Use of systemic corticosteroids or immunosuppressants should be avoided prior to starting cemiplimab due to the potential interference with efficacy. They can be used after initiating cemiplimab to treat immune-mediated reactions .
Acetaminophen may affect the response to immune checkpoint inhibitors. Further clinical studies are needed to determine the exact mechanism and the appropriate clinical management (Bessede et al, 2022).
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline and as clinically indicated |
Liver function tests |
Baseline, before each dose and as clinically indicated; frequent with severe toxicity |
Renal function tests |
Baseline, before each dose and as clinically indicated; frequent with severe toxicity |
Blood glucose |
Baseline, before each dose and as clinically indicated; frequent with severe toxicity |
Thyroid function tests |
Baseline, before each dose and as clinically indicated |
Clinical toxicity assessment for infusion-related reactions, immune-related reactions, including GI, endocrine, skin, neurologic, cardiac, respiratory, ocular and musculoskeletal effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Cemiplimab - Metastatic or Locally Advanced Cutaneous Squamous Cell Carcinoma
Bessede A, Marabelle A, Guegan JP, et al. Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. Ann Oncol 2022;33(9):909-15.
Migden MR, Khushalani K, Chang ALS, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020 Feb;21(2):294-305.
Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 2018;379:341-51.
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Antiemesis: Version 2.2020, 2020.
Prescribing information: Libtayo (cemiplimab). Regeneron Pharmaceuticals, Inc. June 2020.
Product information: Libtayo (cemiplimab). Regeneron Ireland DAC. May 20, 2020.
Product monograph: Libtayo (cemiplimab). Sanofi-Aventis Canada Inc. August 15, 2023.
December 2023 Modified Pharmacokinetics, Indications, Adverse effects, Dosage in hepatic and renal impairment, Dosage in the elderly, Pregnancy/lactation, and Monitoring sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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