PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
AuthorMigden, Michael R.
Schmults, Chrysalyne D.
Lewis, Karl D.
Chung, Christine H.
Lim, Annette M.
Chang, Anne Lynn S.
Thai, Alesha A.
Dunn, Lara A.
Hughes, Brett G.M.
Khushalani, Nikhil I.
Babiker, Hani M.
Johnson, Melissa L.
Owonikoko, Taofeek K.
Papadopoulos, Kyriakos P.
Yancopoulos, George D.
Fury, Matthew G.
AffiliationUniv Arizona, Ctr Canc
MetadataShow full item record
PublisherMASSACHUSETTS MEDICAL SOC
CitationN Engl J Med 2018;379:341-51. DOI: 10.1056/NEJMoa1805131
JournalNEW ENGLAND JOURNAL OF MEDICINE
RightsCopyright © 2018 Massachusetts Medical Society
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBACKGROUND No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. CONCLUSIONS Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors.
Note6 month embargo; published online: 26 July 2018
VersionFinal published version
SponsorsRegeneron Pharmaceuticals; Sanofi