Cemiplimab

The PD-1 antibody cemiplimab belongs to the pharmacological class of immuno-oncologics and is used to treat metastatic and locally advanced cutaneous squamous cell carcinoma that is no longer eligible for curative surgery or radiotherapy. Cemiplimab is directed against the immune checkpoint receptor PD-1 and boosts the T-cell response.

Cutaneous squamous cell carcinoma is the second most common neoplasm of the skin in the white population after basal cell carcinoma. The incidence is increasing, which is due to the ageing population on the one hand and increasing chronic UV exposure in the last 2-3 generations on the other. Consequently, cSCC occurs most frequently on sun-exposed areas such as the face, scalp and back of the hands (Rettig EM et al. 2015). Surgical removal of the tumor can lead to a cure in around 95 percent of patients. The standard treatment for cSCC is complete tunmorresection, preferably using microscopically controlled surgery (Hempel C et al. 2025). Radiotherapeutic procedures are an alternative. Systemic therapy is necessary for locally advanced carcinomas and metastatic cSCC. Since June 2019, the monoclonal PD-1 (programmed cell death) antibody cemiplimab has been approved as a monotherapeutic agent for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are no longer eligible for curative surgery or curative radiotherapy.

The antibody is currently also used in numerous other tumor entities such as non-small cell lung cancer, melanoma, colorectal cancer, prostate cancer, cervical cancer, multiple myeloma and Hodgkin's and non-Hodgkin's lymphoma.

Cemiplimab exhibits linear and dose-proportional kinetics at dosing regimens of 1 mg/kg to 10 mg/kg every 2 weeks and 350 mg every 3 weeks, indicating saturation of the target-mediated pathway. Similar exposures to cemiplimab were observed at doses of 350 mg every 3 weeks and 3 mg/kg every 2 weeks, respectively. At 350 mg every 3 weeks, the mean steady-state concentration of cemiplimab ranged from a Cmax of 168 mg/l to a Ctrough of 61 mg/l. Steady-state exposure is reached after approximately 4 months of treatment.

Absorption: Due to the intravenous application of cemiplimab, the antibody is completely bioavailable.

Distribution: Cemiplimab is predominantly distributed in the vascular system and has a volume of distribution at steady state of 5.2 liters.

Biotransformation: It can be assumed that cemiplimab is degraded to small peptides and single amino acids.

Elimination: At doses of 1 mg/kg to 10 mg/kg every two weeks, cemiplimab is eliminated linearly. After the first dose, the clearance of cemiplimab is approximately 0.33 L/day. Total clearance appears to decrease over time by approximately 35%, resulting in a steady-state clearance of 0.21 l/day. The decrease in clearance is not considered clinically relevant.

The half-life between doses at steady state is 19.4 days.

Cemiplimab is administered as an intravenous infusion over a period of 30 minutes using a sterile, pyrogen-free in-line or add-on filter (0.2 μm to 5 μm pore size) with low protein binding.

Cutaneous squamous cell carcinoma is the second most common neoplasm of the skin in the white population after basal cell carcinoma. The incidence is increasing, which is due to the ageing population on the one hand and increasing chronic UV exposure in the last 2-3 generations on the other. Consequently, cSCC occurs most frequently on sun-exposed areas such as the face, scalp and back of the hands (Rettig EM et al. 2015). Surgical removal of the tumor can lead to a cure in about 95 percent of patients. The standard treatment for cSCC is complete tunmorresection, preferably using microscopically controlled surgery (Hempel C et al. 2025). Radiotherapeutic procedures are an alternative. Systemic therapy is necessary for locally advanced carcinomas and metastatic cSCC.

Since June 2019, the monoclonal PD-1 (programmed cell death) antibody cemiplimab has been approved as a monotherapeutic agent for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are no longer eligible for curative surgery or curative radiotherapy.

The antibody is currently also used in numerous other tumor entities such as non-small cell lung cancer, melanoma, colorectal cancer, prostate cancer, cervical cancer, multiple myeloma and Hodgkin's and non-Hodgkin's lymphoma.

The recommended dose is 350 mg cemiplimab every 3 weeks and should be administered as an intravenous infusion over a period of 30 minutes. Treatment may be continued until disease progression or unacceptable toxicity occurs. Further detailed guidelines on the treatment of immune-mediated adverse reactions can be found in the Information for healthcare professionals.

Severe and fatal immune-mediated adverse reactions that can affect any organ system have been observed during the use of cemiplimab. Most of these immune-mediated reactions occur during treatment with cemiplimab, but may also occur after discontinuation.

Immune-mediated side effects should be treated by adjusting cemiplimab treatment, with hormone replacement therapy (if clinically indicated) and with corticosteroids. Depending on the severity of the side effect, treatment with cemiplimab may need to be temporarily interrupted or permanently discontinued.

During the use of cemiplimab, very frequent (≥ 1/10) cases of:

diarrhea

pruritus

fatigue

Immune-mediated adverse reactions occurred in 20.1% of patients treated with cemiplimab in clinical trials, which led to permanent discontinuation of cemiplimab in 4.4% of patients.

The most common immune-mediated side effects were:

• Hypothyroidism (7.1%)
• pneumonitis (3.7%)
• immune-mediated adverse reactions of the skin (2.0%)
• hyperthyroidism (1.9%)
• Hepatitis (1.9%)

Immune-related colitis (grade 3) - single observation

Furthermore, severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been described in connection with cemiplimab treatment. Exacerbation of psoriasis has been reported with cemiplkimab therapy (Hempel C et al. 2025)

No pharmacokinetic studies have been conducted to detect drug-drug interactions with cemiplimab. Due to potential adverse effects on the pharmacodynamic activity and efficacy of cemiplimab, systemic use of corticosteroids or immunosuppressive agents should be avoided prior to initiation of therapy with cemiplimab, except for physiologic doses of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent). However, after starting therapy with cemiplimab, systemic corticosteroids or other immunosuppressants can be used to treat immune-mediated side effects.

Cemiplimab must not be used in cases of known hypersensitivity to the active substance.

^Libtayo®

Cemiplimab is the third available PD-1 antibody after pembrolizumab and nivolumab. However, its indication differs from that of the other two.

• Hempel C et al. (2025) Clinical and histopathological features of advanced cutaneous squamous cell carcinoma with varying responses to cemiplimab. J Dtsch Dermatol Ges 23:30-37.
• Meliante PG et al. (2023) Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives. Curr Issues Mol Biol 45:9215-9233.
• Botticelli A et al.(2021) Anti-PD-1 and Anti-PD-L1 in Head and Neck Cancer: A Network Meta-Analysis. Front. Immunol 12:705096.
• Devaraja K et al. (2023) Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review. Vaccines 11:634.
• Gambichler T et al. (2021) Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma. Curr Oncol 28:3316-3322.
• Rettig EM et al.(2015) Epidemiology of Head and Neck Cancer. Surg Oncol Clin N Am 24:379-396.