While the vast majority of patients with cutaneous squamous cell carcinoma (CSCC) are cured with surgery, approximately 5% develop advanced disease. Currently there are no systemic therapies approved for treatment of advanced CSCC, and most patients receive palliative care. Because CSCC occurs commonly in immunosuppressed patients and is associated with a high tumor mutation burden, there is strong rationale for immunotherapy in these patients. Cemiplimab is a highly potent new PD-1 inhibitor. In the dose escalation portion of a phase I/II trial, cemiplimab induced durable responses in patients with advanced CSCC. Results from the dose expansion and phase II portions of this trial were presented during the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting in June and simultaneously published in The New England Journal of Medicine.
For both the phase I and phase II portions of the trial, patients received cemiplimab intravenously at a dose of 3mg/kg every 2 weeks. In the phase I dose expansion cohort, 13 of 26 patients (50%) responded to treatment. In the phase II trial population, which comprised of 59 patients with metastatic disease, the objective response rate (ORR) assessed by independent central review was 47.5%. This included 24 (40.7%) complete responses and 4 (6.8%) partial responses. The ORR was 57.7% in patients who were treatment-naïve and 39.4% in previously treated patients. The median duration of response has not yet been reached, though 57% of responders had a response lasting 6 months or longer, and 82% remain in response and continuing cemiplimab treatment at a median follow-up of 7.9 months. The median progression free survival (PFS) and overall survival (OS) had not been reached at the time of data cutoff. The estimated probability of PFS at 12 months was 53% and for OS was 81%.
Grade ≥3 adverse events (AEs) occurred in 42% of patients in the phase II portion of the study. The most common AEs of any grade occurring in ≥15% of patients include diarrhea (27%), fatigue (24%), nausea (17%), constipation (15%), and rash (15%). Four patients (7%) discontinued treatment due to AEs.
The investigators concluded that cemiplimab has substantial activity in advanced CSCC, with durable responses and a tolerable safety profile. The United States Food and Drug Administration has granted priority review status to cemiplimab for CSCC, and a decision is expected by October 2018.