Michael R Migden1, Danny Rischin1, Chrysalyne D Schmults1, Alexander Guminski1, Axel Hauschild1, Karl D Lewis1, Christine H Chung1, Leonel Hernandez-Aya1, Annette M Lim1, Anne Lynn S Chang1, Guilherme Rabinowits1, Alesha A Thai1, Lara A Dunn1, Brett G M Hughes1, Nikhil I Khushalani1, Badri Modi1, Dirk Schadendorf1, Bo Gao1, Frank Seebach1, Siyu Li1, Jingjin Li1, Melissa Mathias1, Jocelyn Booth1, Kosalai Mohan1, Elizabeth Stankevich1, Hani M Babiker1, Irene Brana1, Marta Gil-Martin1, Jade Homsi1, Melissa L Johnson1, Victor Moreno1, Jiaxin Niu1, Taofeek K Owonikoko1, Kyriakos P Papadopoulos1, George D Yancopoulos1, Israel Lowy1, Matthew G Fury1. 1. From the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston (M.R.M.), and South Texas Accelerated Research Therapeutics (START), San Antonio (K.P.P.) - both in Texas; the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (D.R., A.A.T.), the Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, VIC (A.G.), the Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA (A.M.L.), and Royal Brisbane and Women's Hospital and University of Queensland, Brisbane (B.G.M.H.) - all in Australia; the Department of Dermatology, Brigham and Women's Hospital (C.D.S.), the Department of Dermatology, Harvard Medical School (C.D.S.), and the Department of Medical Oncology, Dana-Farber Cancer Institute (G.R.) - all in Boston; Schleswig-Holstein University Hospital, Kiel (A.H.), and University Hospital Essen, Essen and German Cancer Consortium, Essen (D.S.) - both in Germany; University of Colorado Denver, School of Medicine, Aurora (K.D.L.); the Departments of Head and Neck-Endocrine Oncology (C.H.C.) and Cutaneous Oncology (N.I.K.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis (L.H.-A.); the Department of Dermatology, Stanford University School of Medicine, Redwood City (A.L.S.C.), and the Division of Dermatology, City of Hope, Duarte (B.M.) - both in California; the Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York (L.A.D.), and Regeneron Pharmaceuticals, Tarrytown (F.S., M.M., K.M., G.D.Y., I.L., M.G.F.) - both in New York; Regeneron Pharmaceuticals, Basking Ridge, NJ (B.G., S.L., J.L., J.B., E.S.); University of Arizona Cancer Center, Tucson (H.M.B.), and Banner MD Anderson Cancer (J.H.) and the Department of Medical Oncology, Banner MD Anderson Cancer Center (J.N.), Gilbert - all in Arizona; Medical Oncology Department, Vall D'Hebron University Hospital (I.B.), and Institut Català D'Oncologia, Oncobell Program (IDIBELL), L'Hospitalet de Llobregat (M.G.-M.), Barcelona, and START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid (V.M.) - all in Spain; Sarah Cannon Research Institute, Nashville (M.L.J.); and the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta (T.K.O.).
Abstract
BACKGROUND: 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. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
BACKGROUND: 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. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
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