Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma
Neil D. Gross, David M. Miller, Nikhil I. Khushalani, Vasu Divi, Emily S. Ruiz, Evan J. Lipson, Friedegund Meier, Yungpo B. Su, Paul Swiecicki, Jennifer Atlas, J.L. Geiger, Axel Hauschild, Jennifer H. Choe, Brett Hughes, Dirk Schadendorf, Vishal Patel, Jade Homsi, Janis M. Taube, Annette M. Lim, Renata Ferrarotto, Howard L. Kaufman, Frank Seebach, Israel Lowy, Suk‐Young Yoo, Melissa Mathias, Keilah Fenech, Hyunsil Han, Matthew G. Fury, Danny Rischin
Abstract
BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).