文章 :

帕博利珠单抗与伏立诺他联合治疗复发性和/或转移性鳞状细胞癌患者的疗效：一项2期篮式临床试验

Efficacy of pembrolizumab and vorinostat combination in patients with recurrent and/or metastatic squamous cell carcinomas: a phase 2 basket trial

原文发布日期：2025-06-30

英文摘要：

Immune checkpoint inhibitors improve the treatment of many solid tumors and have shown encouraging results in advanced squamous cell carcinoma (SCC), yet only a minority of patients respond to immune checkpoint inhibitor monotherapy. We conducted the PEVOsq trial, an open-label, nonrandomized, multicenter, basket phase 2 trial to evaluate the combination of pembrolizumab and vorinostat in recurrent/metastatic SCC of various origins. The primary endpoint was the objective response rate (ORR) in each tumor cohort during treatment as per the investigators’ assessment. Secondary endpoints included safety and antitumor activity evaluation in terms of centrally confirmed ORR, progression-free survival, overall survival and duration of response. In the efficacy population (n = 107), the ORR was met in cervical (39%), anal (31%) and vulvar/vaginal (19%) cancer cohorts, but not in head and neck SCC (19%) or penile (18%) cancer cohorts (overall ORR = 26%). Median progression-free survival was 4.0 months (95% confidence interval: 2.6–4.3), and median overall survival was 11.1 months (95% confidence interval: 9.2–17.4). In the safety population, 101 (91%) of 111 patients developed at least one treatment-related adverse event, with 39% and 5.4% of patients experiencing at least one grade 3 and grade 4 treatment-related adverse event, respectively. Vorinostat-related toxicity prompted a dose reduction/interruption in 66% of patients. Whole-exome sequencing analyses revealed several potential predictive biomarkers of response to treatment. Further studies in a larger number of patients are required to validate these findings. ClinicalTrials.gov identifier: NCT04357873.

摘要翻译：

免疫检查点抑制剂改善了多种实体瘤的治疗效果，在晚期鳞状细胞癌（SCC）治疗中展现出令人鼓舞的疗效，但单药治疗仅能使少数患者获益。我们开展了PEVOsq试验——一项开放标签、非随机、多中心、篮式II期临床试验，旨在评估帕博利珠单抗联合伏立诺他在不同来源复发/转移性SCC中的疗效。主要终点为研究者评估的各肿瘤队列治疗期间的客观缓解率（ORR）。次要终点包括安全性及通过中心实验室确认的ORR、无进展生存期、总生存期和缓解持续时间评估的抗肿瘤活性。在疗效分析人群（n=107）中，宫颈癌（39%）、肛门癌（31%）和外阴/阴道癌（19%）队列达到ORR终点，但头颈部SCC（19%）和阴茎癌（18%）队列未达标（总体ORR=26%）。中位无进展生存期为4.0个月（95%置信区间：2.6-4.3），中位总生存期为11.1个月（95%置信区间：9.2-17.4）。安全性分析人群中，111例患者有101例（91%）出现至少1例治疗相关不良事件，其中39%和5.4%的患者分别发生≥3级和4级治疗相关不良事件。66%患者因伏立诺他相关毒性需减量或中断治疗。全外显子组测序分析揭示了多个潜在的治疗反应预测生物标志物。后续需扩大样本量进一步验证这些发现。临床试验注册号：NCT04357873。

原文链接:

 https://www.nature.com/articles/s43018-025-01004-2