TY - JOUR
T1 - Cemiplimab in locally advanced cutaneous squamous cell carcinoma
T2 - results from an open-label, phase 2, single-arm trial
AU - Migden, Michael R.
AU - Khushalani, Nikhil I.
AU - Chang, Anne Lynn S.
AU - Lewis, Karl D.
AU - Schmults, Chrysalyne D.
AU - Hernandez-Aya, Leonel
AU - Meier, Friedegund
AU - Schadendorf, Dirk
AU - Guminski, Alexander
AU - Hauschild, Axel
AU - Wong, Deborah J.
AU - Daniels, Gregory A.
AU - Berking, Carola
AU - Jankovic, Vladimir
AU - Stankevich, Elizabeth
AU - Booth, Jocelyn
AU - Li, Siyu
AU - Weinreich, David M.
AU - Yancopoulos, George D.
AU - Lowy, Israel
AU - Fury, Matthew G.
AU - Rischin, Danny
N1 - Funding Information:
This study was funded by Regeneron Pharmaceuticals and Sanofi. We thank the patients, their families, all other investigators, and all investigational site members involved in this study. We also thank Q 2 Solutions EA Genomics, Morrisville, NC, USA, for doing the tumour mutational burden analysis. Nikita Mehta and Robert Charnas from the study sponsors reviewed and provided editorial comments on the manuscript. Medical writing and editorial support under the direction of the authors was provided by Emmanuel Ogunnowo of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals and Sanofi according to Good Publication Practice guidelines. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.
Funding Information:
MRM has received honoraria from Regeneron Pharmaceuticals, Sanofi, Novartis, Genentech, Eli Lilly, and Sun Pharma. NIK has received grants from Regeneron Pharmaceuticals; grants and advisory board fees from Bristol-Myers Squibb and HUYA Bioscience International; advisory board fees from EMD Serono, Regeneron Pharmaceuticals, Genentech, AstraZeneca (data safety monitoring committee), Merck, Array BioPharma, and Immunocore; grants from Merck, Novartis, GlaxoSmithKline, Cellgene, and Amgen; honorarium from Sanofi; and common stock ownership of Bellicum Pharmaceuticals, Mazor Robotics, Amarin, and Transenetrix. ALSC has received fees for being an expert panel member at Regeneron Pharmaceuticals and Merck. KDL has fulfilled consulting and advisory roles at Array BioPharma, Merck, Roche, and Regeneron Pharmaceuticals; received honoraria from Incyte and Array BioPharma, and research funding from Roche, Merck, Incyte, Array BioPharma, Nektar, Iovance Biotherapeutics, and Bristol-Myers Squibb. CDS is a steering committee member for Castle Biosciences; a steering committee member and consultant for Regeneron Pharmaceuticals; a consultant for Sanofi; has received research funding from Castle Biosciences, Regeneron Pharmaceuticals, Novartis, Genentech, and Merck; and is a chair for the National Comprehensive Cancer Network. LH-A has fulfilled consulting and advisory roles at Massive Bio; speakers' bureau roles at Sanofi and Regeneron Pharmaceuticals, and received travel, accommodations, and expenses from Regeneron Pharmaceuticals, Sanofi, and Bristol-Myers Squibb; and research funding from Bristol-Myers Squibb, Regeneron Pharmaceuticals, Immunocore, Merck Sharp & Dohme, Polynoma, Corvus Pharmaceuticals, Roche, Merck Serono, Amgen, MedImmune, and Takeda. DS has received fees for consulting or advisory roles, honoraria, and travel, accommodation and expenses from Roche/Genentech and Merck Serono; fees for consulting or advisory roles, honoraria, speaker's bureau, research funding, and travel, accommodation, and expenses from Novartis and Bristol-Myers Squibb; fees for consulting or advisory roles, honoraria, speaker's bureau from Merck Sharp & Dohme, Incyte and Pierre Fabre; fees for consulting or advisory roles, honoraria, speaker's bureau, and travel, accommodation and expenses from Amgen; fees for consulting or advisory roles and honoraria from Immunocore and 4SC; fees for consulting or advisory roles from Mologen, Sanofi, and Regeneron Pharmaceuticals; speaker's bureau fees from Roche; travel, accommodation, and expenses from Merck; and honoraria from Sysmex, Grünenthal Group, Agenus, Array BioPharma, AstraZeneca, LEO Pharma, Pfizer, Philogen, Regeneron Pharmaceuticals, and Mologen. AG has received personal fees (advisory board and travel support) from Bristol-Myers Squibb, Sun Pharma, and Merck, and advisory boards fees from Eisai, Sanofi, Pfizer, and Roche. AH has received institutional grants, speaker's honoraria, and consultancy fees from Amgen, Bristol-Myers Squibb, MSD/Merck, Pierre Fabre, Provectus, Sanofi Genzyme, Roche, Regeneron Pharmaceuticals, and Novartis, institutional grants and consultancy fees from Merck Serono and Philogen, and consultancy fees from Sun Pharma and OncoSec. DJW has received institutional research grant funding from Regeneron Pharmaceuticals, grants and personal fees from Bristol-Myers Squibb and Genentech, and grants from ARMO BioSciences, Merck Sharp & Dohme, Kura Oncology, AstraZeneca, and Regeneron Pharmaceuticals. GAD has received speaker fees from Regeneron Pharmaceuticals. CB has received an institutional research grant from Regeneron Pharmaceuticals; grants, personal fees, and non-financial support for consulting, lectures, and clinical trials from Amgen, Bristol-Myers Squibb, MSD, Novartis, and Roche; personal fees and non-financial support for consulting from Pierre Fabre, Sanofi Aventis, and Merck; a grant for a clinical trial from Array and personal fees (safety monitoring board) from Miltenyi. VJ, ES, JB, SL, DMW, IL, and MGF are employees and shareholders of Regeneron Pharmaceuticals. GDY is an employee, shareholder of, and member of Board of Directors at Regeneron Pharmaceuticals. DR has received an institutional research grant and funding from Regeneron Pharmaceuticals, Merck, Roche, GlaxoSmithKline, and Bristol-Myers Squibb, and uncompensated advisory board participation for Merck, Regeneron Pharmaceuticals, GlaxoSmithKline, Amgen, and Bristol-Myers Squibb; and travel support from Merck. FM declares no competing interests.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/2
Y1 - 2020/2
N2 - Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma. Methods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498. Findings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1–15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32–55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3–4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia. Interpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care. Funding: Regeneron Pharmaceuticals and Sanofi.
AB - Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma. Methods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498. Findings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1–15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32–55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3–4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia. Interpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care. Funding: Regeneron Pharmaceuticals and Sanofi.
UR - http://www.scopus.com/inward/record.url?scp=85078679193&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(19)30728-4
DO - 10.1016/S1470-2045(19)30728-4
M3 - Article
C2 - 31952975
AN - SCOPUS:85078679193
VL - 21
SP - 294
EP - 305
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 2
ER -