西妥昔单抗治疗转移性皮肤鳞状细胞癌的 2 期研究：固定剂量、体重为基础剂量的长期结局的初步分析。
Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing.
机构信息
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
出版信息
J Immunother Cancer. 2020 Jun;8(1). doi: 10.1136/jitc-2020-000775.
BACKGROUND
Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).
METHODS
The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.
RESULTS
For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).
CONCLUSION
In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.
TRIAL REGISTRATION NUMBER
Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498.
背景
程序性死亡受体-1（PD-1）的高亲和力、强效人源化 IgG4 单克隆抗体 cemiplimab 在一项 1 期晚期皮肤鳞状细胞癌（CSCC）扩展队列（NCT02383212）和关键 2 期研究（NCT02760498）中显示出抗肿瘤活性。在此，我们报告了关键性 2 期研究中转移性 CSCC（mCSCC）患者静脉内固定剂量 cemiplimab 350mg，每 3 周（Q3W）（第 3 组）的主要分析，并在第 1 组的主要分析后提供更长时间的更新，第 1 组为基于体重的 cemiplimab 3mg/kg，每 2 周（Q2W）静脉内给药（第 1 组）（NCT02760498）。
方法
每组的主要目的是独立中心审查（ICR）的客观缓解率（ORR）。次要终点包括研究者评估（INV）的 ORR、ICR 和 INV 的缓解持续时间（DOR）以及安全性和耐受性。
结果
对于第 3 组（n=56）和第 1 组（n=59），中位随访时间分别为 8.1 个月（范围，0.6 至 14.1）和 16.5 个月（范围，1.1 至 26.6）。第 3 组 ICR 的 ORR 为 41.1%（95%可信区间，28.1%至 55.0%），第 1 组为 49.2%（95%可信区间，35.9%至 62.5%），两组联合为 45.2%（95%可信区间，35.9%至 54.8%）。根据 ICR，第 3 组应答患者的 DOR 估计值在 8 个月时为 95.0%（95%可信区间，69.5%至 99.3%），在 12 个月时为 88.9%（95%可信区间，69.3%至 96.3%）。根据 INV，第 3 组的 ORR 为 51.8%（95%可信区间，38.0%至 65.3%），第 1 组为 49.2%（95%可信区间，35.9%至 62.5%），两组联合为 50.4%（95%可信区间，41.0%至 59.9%）。无论归因如何，最常见的不良反应是疲劳（27.0%）和腹泻（23.5%）。
结论
在转移性 CSCC 患者中，静脉内 cemiplimab 350mg，每 3 周给药一次，可产生显著的抗肿瘤活性，具有持久的缓解和可接受的安全性特征。静脉内 cemiplimab 3mg/kg，每 2 周给药一次的随访数据显示，应答持续时间长。
临床试验注册号
Clinicaltrials.gov，NCT02760498。注册于 2016 年 5 月 3 日，https://clinicaltrials.gov/ct2/show/NCT02760498。
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