PURPOSE This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer (SGC). PATIENTS AND METHODS Patients with progressing incurable HN and SGC, Eastern Cooperative Oncology Group (ECOG) ≤1, no prior immunotherapy, RECIST1.1 measurable disease, and normal organ function were eligible. Pembrolizumab 200 mg was given intravenous every 21 days, and vorinostat 400 mg given orally 5 days on and 2 days off during each 21-day cycle. Primary endpoints were safety and objective response rates. RESULTS From November 2015 to August 2017, 25 patients with HN and 25 SGC were enrolled. Median age was 61 (range, 33-86) years, 39 (78%) were male, 21 (62%) were never smokers, and 27 (54%) had ECOG 0. In HN, 13 (52%) were p16+ oropharynx. Most common SGC histologies were adenoid cystic 12 (48%), acinic cell 3 (12%), and mucoepidermoid 3 (12%). Adverse events (AEs) in all patients were: 27 (54%) with grade ≥ 1 and 18 (36%) with grade ≥ 3. The most common AEs in all patients were renal insufficiency in seven, (14%), fatigue in six, (12%), and nausea in three (6%). There were three (12%) deaths on study. Responses in HN were complete response (CR) 0, partial response (PR) eight (32%), and stable disease (SD) five (20%). Efficacy in SGCs was CR 0, PR four (16%) in one lymphoepithelioma-like carcinoma, two acinic cell, one adenoid cystic, and SD 14 (56%). In the HN group, median follow-up (mFUP) was 12.6 months, median overall survival (mOS) was 12.6 months, and median progression-free survival (mPFS) was 4.5 months. In SGC, mFUP was 13.1 months, mOS was 14.0 months, and mPFS was 6.9 months. CONCLUSIONS This combination demonstrated activity in HN, with fewer responses in SGC. Toxicities were higher than reported with pembrolizumab alone.

中文翻译：

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Pembrolizumab和Vorinostat在复发性转移性头颈部鳞状细胞癌和唾液腺癌中的II期试验。

目的这项临床试验将派姆单抗和伏立诺他合用在复发/转移性头颈部鳞状细胞癌（HN）和唾液腺癌（SGC）中。患者和方法患有无法治愈的HN和SGC，东部合作肿瘤小组（ECOG）≤1，未进行过免疫治疗，RECIST1.1可测量的疾病以及正常器官功能的患者均符合条件。在每个21天的周期中，每21天静脉给予一次Pembrolizumab 200 mg，伏立诺他400 mg口服，持续时间分别为5天和2天。主要终点是安全性和客观反应率。结果从2015年11月至2017年8月，招募了25例HN和25例SGC患者。中位年龄为61岁（范围：33-86岁），男性为39（78％），从不吸烟者为21（62％），ECOG 0为27（54％）。在HN中，p16 +为13（52％）口咽。最常见的SGC组织学是腺样囊性12（48％），腺泡细胞3（12％）和粘液表皮样3（12％）。所有患者的不良事件（AEs）为：27（54％）≥1级和18（36％）≥3级。所有患者中最常见的AEs为肾功能不全的7例（14％），疲乏。六分（12％），三分恶心（6％）。研究中有3例（12％）死亡。HN的反应为完全反应（CR）0，部分反应（PR）8（32％）和稳定疾病（SD）5（20％）。SGCs在一种淋巴上皮瘤样癌，两种腺泡细胞，一种腺样囊性癌和SD 14（56％）中的功效分别为CR 0，PR 4（16％）。在HN组中，中位随访（mFUP）为12.6个月，中位总体生存期（mOS）为12.6个月，中位无进展生存期（mPFS）为4.5个月。在SGC中，mFUP为13.1个月，mOS为14.0个月，mPFS为6。9个月。结论该组合证明在HN中具有活性，而在SGC中的响应较少。毒性高于单独使用派姆单抗的报道。