Programmed death 1 (PD-1) inhibition with the novel human anti-PD1 monoclonal antibody cemiplimab (REGN2810, Regeneron and Sanofi) in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma (CSCC) resulted in a response in approximately half of the patients.¹Migden MR, et al. N Engl J Med. 2018; DOI: 10.1056/NEJMoa1805131^,2Sanofi (2018, April 30) [Press release] retrieved from http://www.news.sanofi.us/2018-04-30-FDA-to-Conduct-Priority-Review-of-Cemiplimab-as-a-Potential-Treatment-for-Advanced-Cutaneous-Squamous-Cell-Carcinoma

Advanced CSCC has the highest mortality among non-melanoma skin cancer. It is the second most common cancer of the skin in the Chinese and Japanese population, with an annual incidence in Asians ranging from 1.3 (Malay) to 2.6 (Chinese) per 100,000.³Kim GK, et al. J Clin Aesthet Dermatol. 2009; 2(8): 39–42. There are no approved systemic therapies for the treatment of advanced CSCC.

"This cancer may be responsive to immune therapy, because the mutation burden of the tumour is high and the disease risk is strongly associated with immunosuppression," wrote the authors in the New England Journal of Medicine.

The pooled analysis includes two studies; a metastatic-disease cohort with cemiplimab from the pivotal Phase II EMPOWER-CSCC 1 trial (NCT02760498) and an expansion cohort of patients with locally advanced or metastatic CSCC from a Phase I study (NCT02383212) with cemiplimab in solid malignancies. In both trials, patients were treated every 2 weeks with an intravenous dose of cemiplimab (3 mg/kg) and assessed for responses every 8 weeks. The primary endpoint in the Phase II EMPOWER-CSCC 1 trial was the response rate by an independent central review.

Results

In the Phase 1 expansion cohort study in patients with locally advanced or metastatic CSCC, cemiplimab was associated with a response in 50% (13/26) of patients (95% CI, 30-70). In the Phase 2 metastatic-disease cohort, responses were reported in 47% (28/59) of patients (95% CI, 34-61). At a median follow-up of 7.9 months, the duration of response (DoR) among the 28 responders in the Phase 2 cohort exceeded 6 months in 57% (16/28) of patients. At the time of data cutoff, 82% of responders continued cemiplimab with ongoing responses.

Safety

The safety profile was comparable with the toxicities reported in other studies with immune-checkpoint inhibitors. Common adverse events (AEs) in ≥15% of patients in the Phase II metastatic-disease cohort were diarrhoea, fatigue, nausea, constipation, and rash. AEs led to discontinuation in 7% of the patients.

References

1. Migden MR, et al. N Engl J Med. 2018; DOI: 10.1056/NEJMoa1805131.
2. Sanofi (2018, April 30) [Press release] retrieved from http://www.news.sanofi.us/2018-04-30-FDA-to-Conduct-Priority-Review-of-Cemiplimab-as-a-Potential-Treatment-for-Advanced-Cutaneous-Squamous-Cell-Carcinoma.
3. Kim GK, et al. J Clin Aesthet Dermatol. 2009; 2(8): 39–42.