What is cemiplimab?
Cemiplimab (also called cemiplimab-rwlc; trade name Libtayo®; Regeneron Pharmaceuticals Inc., New York, USA) is a monoclonal antibody used for patients with advanced cutaneous squamous cell carcinoma (SCC).
Cemiplimab was approved by the US Food and Drug Administration (FDA) for patients with metastatic cutaneous SCC or locally advanced cutaneous SCC who are not candidates for curative surgery or curative radiation.
Cemiplimab was evaluated by the FDA under priority review, which is reserved for medicines that represent significant improvements in safety or efficacy in treating serious conditions.
Cemiplimab is the first and only treatment specifically approved and available for advanced cutaneous SCC in the US. Regeneron and Sanofi-Aventis (New Jersey, USA) will market cemiplimab jointly in the US. Cemiplimab belongs to a class of agents known as immune checkpoint inhibitors, that work by strengthening the body’s immune response to tumours.
In April 2018, the European Medicines Agency (EMA) accepted for review the marketing authorization application for cemiplimab for the treatment of patients with metastatic cutaneous SCC or with locally advanced SCC who are not candidates for surgery.
The EMA review process is anticipated to be complete by the first half of 2019. There are currently no EMA-approved treatments for advanced cutaneous SCC. Regulatory applications in additional countries are also currently being considered for submission.
Cemiplimab is currently unavailable in New Zealand.
Clinical trial evidence for cemiplimab
Pivotal advanced cutaneous SCC clinical program results
The FDA approval of cemiplimab was based on a combined analysis of data from an open-label, multicentre, non-randomised Phase II trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced cutaneous SCC expansion cohorts from a multicentre, open-label, non-randomised Phase I trial (Study 1423). Together, these trials represented the largest prospective data set in advanced cutaneous SCC.
The major efficacy outcome measures for EMPOWER-CSCC-1 and the two cutaneous SCC expansion cohorts were confirmed objective response rate (ORR) as assessed by an independent central review (ICR) and ICR-assessed duration of response.
For patients with metastatic cutaneous SCC without externally visible target lesions, ORR was determined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). For patients with externally visible target lesions (locally advanced and metastatic cutaneous SCC), ORR was determined by a composite endpoint that integrated ICR assessments of radiological data (RECIST 1.1) and digital medical photography (World Health Organisation criteria).
The efficacy analysis was conducted when all patients had the opportunity for at least 6 months of follow-up.
Patients received cemiplimab 3 mg/kg intravenously every 2 weeks for up to 48 weeks in Study 1423 or up to 96 weeks in Study 1540. Treatment continued until progression of the disease, unacceptable toxicity, or completion of planned treatment. Tumour response assessments were performed every 8 weeks.
Both studies excluded patients with:
- Autoimmune disease that required systemic therapy with immunosuppressant agents within 5 years
- A history of solid organ transplant
- Prior treatment with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking antibodies or other immune checkpoint inhibitor therapies
- Infection with HIV
- Hepatitis B or hepatitis C
- An Eastern Cooperative Oncology Group performance status ≥ 2.
Combined efficacy results (n = 108) from EMPOWER-CSCC-1 and the two advanced cutaneous SCC expansion cohorts from the Phase 1 trial are summarised in the table below:
| Efficacy Endpoints* | Metastatic CSCC (n =75) | Locally Advanced CSCC (n=33) | Combined CSCC (n=108) |
| Confirmed objective response (ORR) | |||
| ORR (95% confidence interval [CI]) | 47% (35, 59) |
49% (31,67) |
47% (38, 57) |
| Complete response rate† | 5% | 0% | 4% |
| Partial response rate | 41% | 49% | 44% |
| Duration of response (DOR) | |||
| Range in months | 3–15+ | 1–13+ | 1–15+ |
| Patients with DOR > 6 months, n (%) | 21 (60%) | 10 (63%) | 31 (61%) |
* Median duration of follow-up: metastatic CSCC: 8.1 months; locally advanced CSCC: 10.2 months; combined CSCC: 8.9 months
†Includes patients with complete healing of prior cutaneous involvement; locally advanced CSCC patients in EMPOWER-CSCC-1 required biopsy to confirm complete response.
Adverse events
For the combined safety analysis (n = 163) of EMPOWER-CSCC-1 and the two advanced cutaneous SCC expansion cohorts, the most common adverse events reported were:
- Fatigue (29%)
- Rash (25%)
- Diarrhoea (22%).
In 5% of patients, cemiplimab was discontinued permanently due to the following adverse events:
- Pneumonitis
- Autoimmune myocarditis
- Hepatitis
- Aseptic meningitis
- Complex regional pain syndrome
- A cough
- Muscular weakness.
Serious adverse reactions occurred in 28% of patients. SAEs that occurred in at least 2% of patients were:
- Cellulitis
- Sepsis
- Pneumonia
- Pneumonitis
- Urinary tract infection.
Adverse reactions that occured in less than 10% of patients with advanced cutaneous SCC receiving cemiplimab in Study 1423 and Study 1540 include:
- Rash
- Pruritus
- Diarrhoea
- Nausea
- Constipation
- Fatigue
- Musculoskeletal pain
- Decreased appetite.
Laboratory test abnormalities
The Grade 3 and 4 laboratory test abnormalities that worsened from baseline in fewer than 1% of patients with advanced cutaneous SCC who received cemiplimab in Study 1423 and Study 1540 are listed below.
Chemistry
Abnormalities included:
- Increased aspartate transanimase (3%)
- Increased international normalised ratio (2%)
- Hypoalbuminaemia (1%).
Haematology
Abnormalities included:
- Lymphopenia (7%)
- Anaemia (2%).
Electrolytes
Abnormalities included:
- Hypophosphataemia (4%)
- Hyponatraemia (3%)
- Hypercalcaemia (1%).
Cemiplimab – future potential
- Cemiplimab is an important new immunotherapy option for physicians to help address a significant unmet need in patients with advanced cutaneous SCC who are no longer candidates for curative surgery or radiation.
- The safety profile of cemiplimab observed in the trials was consistent with that of other approved anti-PD-1 agents.
- Results of clinical trials concluded that cemiplimab induced a response in approximately half the patients with advanced cutaneous SCC.
- Cemiplimab is currently being studied in Phase III trials for various indications, including metastatic non-small cell lung cancer (NSCLC), advanced NSCLC, cervical cancer, and basal cell carcinoma.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).