Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.,The Lancet Oncology

当前位置： X-MOL 学术 › Lancet Oncol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.
The Lancet Oncology ( IF 41.6 ) Pub Date : 2020-01-14 , DOI: 10.1016/s1470-2045(19)30728-4
Michael R Migden ₁ , Nikhil I Khushalani ₂ , Anne Lynn S Chang ₃ , Karl D Lewis ₄ , Chrysalyne D Schmults ₅ , Leonel Hernandez-Aya ₆ , Friedegund Meier ₇ , Dirk Schadendorf ₈ , Alexander Guminski ₉ , Axel Hauschild ₁₀ , Deborah J Wong ₁₁ , Gregory A Daniels ₁₂ , Carola Berking ₁₃ , Vladimir Jankovic ₁₄ , Elizabeth Stankevich ₁₅ , Jocelyn Booth ₁₅ , Siyu Li ₁₅ , David M Weinreich ₁₄ , George D Yancopoulos ₁₄ , Israel Lowy ₁₄ , Matthew G Fury ₁₄ , Danny Rischin ₁₆

Affiliation

Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Department of Dermatology, Stanford University School of Medicine, Redwood City, CA, USA.
University of Colorado Denver, School of Medicine, Aurora, CO, USA.
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Department of Dermatology, University Hospital Dresden, Dresden, Germany.
University Hospital Essen, Essen and German Cancer Consortium, Essen, Germany.
Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia.
Schleswig-Holstein University Hospital, Kiel, Germany.
UCLA Department of Medicine, Los Angeles, CA, USA.
Division of Hematology and Oncology, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
Department of Dermatology and Allergy, Munich University Hospital (LMU), Munich, Germany.
Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Regeneron Pharmaceuticals, Basking Ridge, NJ, USA.
Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC, Australia.

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.

中文翻译：

塞米普利单抗治疗局部晚期皮肤鳞状细胞癌：来自开放标签的2期单臂试验的结果。

背景技术西米普利单抗在转移性皮肤鳞状细胞癌患者中显示出显着的抗肿瘤活性。常规系统疗法治疗局部晚期皮肤鳞状细胞癌的患者预后较差。我们目前对塞米普利单抗在局部晚期皮肤鳞状细胞癌患者中的安全性和抗肿瘤活性进行初步分析。方法该关键的开放标签，第2期，单臂试验在25个门诊诊所进行，主要在澳大利亚，德国和美国的学术医学中心进行。符合条件的患者（年龄≥18岁，经组织学证实为局部晚期皮肤鳞状细胞癌且东部合作肿瘤小组的工作状态为0-1），每2周静脉注射塞米普利单抗3 mg / kg，每2周一次，持续96周。每8周进行一次肿瘤测量。主要终点是客观反应，根据对放射线扫描的《实体肿瘤1.1版》中的反应评估标准和WHO摄影医学标准进行的独立中央评审，确定为完全或部分反应患者的比例。数据截止日期为2018年10月10日，当时完全入组的人群达到了初步分析的预定时间点。根据意向治疗原则进行分析。安全性分析包括所有接受至少一剂西米普利单抗的患者。该研究已在ClinicalTrials.gov上注册，编号为NCT02760498。结果在2016年6月14日至2018年4月25日之间，有78例患者接受了西米普利单抗治疗。数据截止时研究随访的中位时间为9·3个月（IQR 5·1-15·7）。在78位患者中，有34位（44％； 95％CI 32-55）观察到客观反应。总体反应最好的是十例（13％）的患者，其中完全缓解者为24（31％）的部分反应。在78位患者中，有34位（44％）发生了3-4级紧急治疗事件；最常见的是高血压（6％（8％））和肺炎（4％（5％））。78名患者中有23名（29％）出现了严重的治疗紧急不良事件。据报道，吸入性肺炎发作后发生了一次与治疗有关的死亡。解释在没有被广泛接受的治疗标准的局部晚期皮肤鳞状细胞癌患者中，西米普利单抗显示出抗肿瘤活性和可接受的安全性。

更新日期：2020-01-31

点击分享查看原文

点击收藏

阅读更多本刊新发论文