Background Despite remarkable results with salvage standard-dose or high-dose chemotherapy ∼15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods Single arm phase II trial investigating pembrolizumab 200 mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age ≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT. Clinical trial information NCT02499952.

中文翻译：

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pembrolizumab在铂难治性生殖细胞肿瘤患者中进行的II期临床试验：Hoosier癌症研究网络研究GU14-206。

背景技术尽管采用标准剂量或高剂量化疗获得了显著成果，但仍有约15％的复发性生殖细胞肿瘤（GCT）患者是无法治愈的。免疫检查点抑制剂已在多种肿瘤类型中产生显着缓解。我们报告了对GCT患者进行免疫疗法的第一项研究。患者和方法单臂II期临床试验研究Q3周iv静脉注射派姆单抗200 mg，直至GCT复发且无可治愈选择的患者疾病进展。GCT≥18岁且在一线顺铂为基础的化疗后且至少进行了一种挽救方案（大剂量或标准剂量化疗）后进展的患者是合格的。对肿瘤和浸润的免疫细胞进行集中评估的程序化死亡配体1（PD-L1）评分。主要终点是使用免疫相关反应标准的总体反应率。使用了I型误差为20％，功率为80％的Simon两阶段设计。结果招募了十二名男性患者。中位年龄为38岁。所有患者均患有非性腺瘤。主要部位是睾丸（11）或纵隔（1）。中位数AFP 615（范围为1-32、760）和hCG 4（范围为0.6-37、096）。6例患者复发较晚（> 2年）。先前化疗方案的中位数为3。6例患者接受了先前的大剂量化疗。两名患者的PD-L1染色阳性（H评分90和170）。派姆单抗的中位数为2（范围1至8）。有六个三级不良事件。没有报告与免疫有关的不良事件。没有观察到部分或全部反应。两名患者在28周和19周内均获得了放射学稳定的疾病，分别; 尽管影像学稳定，但两者均持续升高AFP水平，PD-L1染色阴性。结论这是首次报道的评估GCT中免疫检查点抑制剂的试验。派姆单抗具有良好的耐受性，但在难治性GCT中似乎没有具有临床意义的单药活性。临床试验信息NCT02499952。