An immune checkpoint inhibitor already approved for advanced cancers is set to become a new standard of care in the adjuvant setting for high-risk cutaneous squamous cell carcinoma (CSCC) across Europe.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a favorable opinion for Libtayo (cemiplimab, Regeneron Pharmaceuticals) as adjuvant treatment for adults with CSCC at high risk for recurrence after surgery and radiation. 

The recommendation follows compelling results from the global phase 3 C-POST trial, in which Libtayo reduced the risk for disease recurrence or death by 68% compared with placebo. 

CSCC is a nonmelanoma skin cancer that ranks among the most common cancers globally. In the European Union, nonmelanoma skin cancer incidence overall is projected to rise by 40% by 2040. Although surgery often successfully treats it, many patients present with high-risk disease that behaves more aggressively, leading to greater recurrence and progression risks.

The active substance of Libtayo is cemiplimab, a fully human monoclonal antibody that targets the immune checkpoint receptor PD-1 on T cells. Through PD-1 binding, it blocks cancer cells from exploiting the PD-1 pathway to suppress T-cell activation.

Significant Reduction in Recurrence

C-POST enrolled 415 participants, who were then randomly assigned to receive either cemiplimab (n = 209) or placebo (n = 206) for up to 48 weeks. 

Participants faced high recurrence risk due to nodal characteristics such as extracapsular extension or three or more involved lymph nodes, and/or non-nodal characteristics including in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with one or more additional poor prognostic factors.

The treatment protocol involved administration of cemiplimab 350 mg intravenously every 3 weeks for the initial 12 weeks, followed by 700 mg every 6 weeks for the remaining 36 weeks, or placebo. 

At a median follow-up of 24 months, cemiplimab reduced the risk for disease recurrence or death by 68% compared with placebo, which was the primary endpoint. Estimated 24-month disease-free survival reached 87.1% with cemiplimab compared with 64.1% for placebo. Benefits extended across all patterns of recurrence. Locoregional recurrence occurred in 4% of cemiplimab-treated patients vs 17% of placebo recipients, while distant recurrence affected 5% vs 13%, respectively. Disease-free survival events totaled 24 in the cemiplimab arm compared with 65 in the placebo group. 

Safety Profile

The safety profile was consistent with established data for cemiplimab monotherapy in advanced cancers. While adverse events occurred at similar overall rates in both treatment arms (91% with cemiplimab vs 89% with placebo), grade 3 or higher events were more frequent with active treatment (24% vs 14%). 

The most reported adverse events with cemiplimab included fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism, and maculopapular rash. Hypertension was the only grade 3 or higher adverse event occurring in more than 2% of patients in the cemiplimab arm. Adverse events led to permanent treatment discontinuation in 10% of patients receiving cemiplimab compared with 2% of those receiving placebo. Two patients in each treatment arm experienced fatal adverse events.

The positive opinion from the CHMP is an intermediary step because this medicine is under additional monitoring. A final decision on the marketing application from the European Commission is expected in the coming months. This follows an approval for the same indication by the US Food and Drug Administration earlier this month. 

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics, which will be published on the European Medicines Agency’s website in all official EU languages after a decision on this change to the marketing authorization has been granted by the European Commission.