一项关于 cemiplimab 在晚期鳞状细胞皮肤癌患者中的2期开放标签研究（EMPOWER-CSCC-1）：第1、2、3组的最终长期分析及固定剂量治疗组6的主要分析

A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

影响因子:11.8

分区:医学1区 Top / 皮肤病学1区

发表日期:2025 Jan

作者: Brett G M Hughes, Alexander Guminski, Samantha Bowyer, Michael R Migden, Chrysalyne D Schmults, Nikhil I Khushalani, Anne Lynn S Chang, Jean-Jacques Grob, Karl D Lewis, George Ansstas, Fiona Day, Rahul Ladwa, Brian N Stein, Eva Muñoz Couselo, Friedegund Meier, Axel Hauschild, Dirk Schadendorf, Nicole Basset-Seguin, Badri Modi, Sophie Dalac-Rat, Lara A Dunn, Lukas Flatz, Laurent Mortier, Sarah Guégan, Lucie M Heinzerling, Janice M Mehnert, Sabiha Trabelsi, Ainara Soria-Rivas, Alexander J Stratigos, Claas Ulrich, Deborah J Wong, Marie Beylot-Barry, Paolo Bossi, Cristina Bugés Sánchez, Sunandana Chandra, Caroline Robert, Jeffery S Russell, Ann W Silk, Jocelyn Booth, Suk-Young Yoo, Frank Seebach, Israel Lowy, Matthew G Fury, Danny Rischin

DOI: 10.1016/j.jaad.2024.06.108

摘要

在2期EMPOWER-CSCC-1研究（NCT02760498）中，cemiplimab表现出抗转移性鳞状细胞皮肤癌（mCSCC）和局部晚期鳞状细胞癌（laCSCC）的抗肿瘤活性。本研究报告了基于体重的cemiplimab在mCSCC和laCSCC中的最终分析（第1、2组）、固定剂量cemiplimab在mCSCC中的分析（第3组）以及固定剂量cemiplimab在mCSCC/laCSCC中的主要分析（第6组）。患者每2周静脉注射cemiplimab（3 mg/kg，适用于第1、2组）或每3周一次静脉注射（350 mg，适用于第3、第6组）。主要终点为客观反应率（ORR）。反应持续时间（DOR）和无进展生存期（PFS）根据协议和事后敏感性分析进行报告，仅包括协议要求的影像评估期间。在42.5个月的随访中，第1-3组（n=193）的ORR为47.2%，12个月的估计DOR为88.3%，中位PFS为26.0个月；第6组（n=165）在8.7个月时的ORR为44.8%，中位DOR和中位PFS尚未达到。严重治疗相关不良事件（Grade ≥3）发生率：第1-3组为31.1%，第6组为34.5%。本研究为非随机、非生存期主要终点的研究，提供了关于晚期CSCC中抗程序性细胞死亡-1治疗的最长远的疗效和安全性前瞻性数据。

Abstract

In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC).To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (groups 1 and 2), fixed-dose cemiplimab in mCSCC (group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (group 6).Patients received cemiplimab (3 mg/kg intravenously every 2 weeks [groups 1 and 2]) or cemiplimab (350 mg intravenously [groups 3 and 6]) every 3 weeks. The primary end point was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments.At 42.5 months, ORR for groups 1-3 (n = 193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for group 6 (n = 165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were groups 1-3: 31.1% and group 6: 34.5%.Nonrandomized study, nonsurvival primary end point.EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.