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    This open-label multicenter study evaluated the human monoclonal antibody, cemiplimab, for treatment of advanced cutaneous squamous-cell carcinoma. Cemiplimab is a high-affinity monoclonal antibody directed against programmed death 1 (PD-1).

    Study design

    Investigators reported findings from a phase 1 trial and partial results from a phase 2 trial. All participants were ineligible for surgery because of a high risk of complications or had disease recurrence after their first 2 surgeries. Each patient received intravenous cemiplimab (3 mg/kg of body weight) every 2 weeks. Drug response was evaluated every 8 weeks.

    The phase 1 study assessed outcomes of cemiplimab treatment for an expansion cohort with either locally advanced or metastatic cutaneous squamous-cell carcinoma (n=26). The primary endpoint was safety and side-effect profiles, with treatment lasting up to 48 weeks.

    Phase 2 was a nonrandomized, global, pivotal study examining patients with metastatic disease (n=59). Response rate was the primary endpoint and the treatment duration lasted up to 96 weeks or until patient exhibited unacceptable toxic effects or disease progression. Secondary end points for both trials included response duration, progression-free survival, overall survival and toxic effects.


    Results from the phase 1 study showed 50% of patients had a response to cemiplimab and 65% achieved durable disease control. The median time to response was 2.3 months.

    In the phase 2 study, the response rate and durable rate of control were nearly the same as those in phase 1 (47% and 61%, respectively). Four patients exhibited a complete response while 24 had a partial one. Response exceeded 6 months in 57% of patients, and 82% continued to have a response at the time of data cutoff. At 12 months, probability of overall survival (81%) was higher than the estimated probability of progression-free survival (53%).

    Adverse events occurred in at least 15% of patients with metastatic disease, and included diarrhea, fatigue, nausea and rash. Treatment was discontinued in 7% of patients due to an adverse event.


    The full phase 2 results are needed to clarify the clinical role of cemiplimab in this disease. This study involved immunocompetent patients, so the effect of this therapy in immunocompromised patients, who make up an important proportion of patients suffering from life-threatening disease, remains uncertain.

    Clinical significance

    The high mutation burden of cutaneous squamous-carcinoma appears to make this cancer sensitive to effector T-cells in the context of the immune checkpoint blockade produced by cemiplimab. With further study, cemiplimab may become the first approved systemic treatment for cutaneous squamous cell carcinoma. These immune checkpoint inhibitors will likely become an important class of treatments of hypermutated cancers.