Author: Anoma Ranaweera, Medical Writer, Auckland, New Zealand. DermNet Editor in Chief: Adjunct A/Prof Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. November 2018.
In September 2018, the FDA (Food and Drug Administration) approved cemiplimab-rwlc (LIBTAYO®, Regeneron Pharmaceuticals Inc. NY, USA) for patients with metastatic cutaneous squamous cell carcinoma (SCC) or locally advanced cutaneous SCC who were 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 United States. Regeneron and Sanofi-Aventis (New Jersey, USA) will market Libtayo® jointly in the USA. Cemiplimab belongs to a class of agents known as immune checkpoint inhibitors, which 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 being considered for submission later in 2018.
Cemiplimab is currently unavailable in New Zealand.
The FDA approval of cemiplimab was based on a combined analysis of data from an open-label, multicentre, non-randomised Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced cutaneous SCC expansion cohorts from a multicentre, open-label, non-randomised Phase 1 trial (Study 1423). Together, the 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 (DOR).
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 radiologic data (RECIST 1.1) and digital medical photography (WHO criteria).
The efficacy analysis was conducted when all patients had the opportunity for at least six 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; history of solid organ transplant; prior treatment with anti–PD-1/PD-L1 blocking antibodies or other immune checkpoint inhibitor therapy; infection with HIV, hepatitis B or hepatitis C; or ECOG performance score (PS) ≥ 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:
For the combined safety analysis (n=163) of EMPOWER-CSCC-1 and the two advanced cutaneous SCC expansion cohorts, the most common adverse reactions reported were:
In 5% of patients cemiplimab was discontinued permanently due to the following adverse effects:
Serious adverse reactions (SAEs) occurred in 28% of patients. SAEs that occurred in at least 2% of patients were:
Adverse reactions in less than 10% of patients with advanced cutaneous SCC receiving cemiplimab in study 1423 and study 1540 include:
The grade 3 and 4 laboratory abnormalities that worsened from baseline in fewer than 1% of patients with advanced cutaneous SCC receiving cemiplimab in study 1423 and study 1540 are listed here.
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