免疫检查点可以对免疫反应起到调节作用。现在主要的免疫检查点有IDO、CTLA-4和PD-1。目前，FDA已经批准了几种治疗晚期非小细胞肺癌的免疫检查点抑制剂，包括靶向PD-1和PD-L1治疗的BMS的纳武单抗(nivolumab)、MSD的派姆单抗(pembrolizumab)以及罗氏的atezolizumab。患者的治疗效果也因PD-L1的表达水平而异，而且相当一部分患者对于这些免疫检查点抑制剂的治疗并不响应。在黑色素瘤和其他肿瘤患者当中限时免疫检查点抑制剂的联合疗法会增加免疫治疗的效果。吲哚胺2,3-双加氧酶(IDO)是细胞的免疫调节剂，其可以有效抑制癌症患者T细胞的免疫作用。IO102是新开发的一种合成肽，为IDO的抑制剂，一项小型的单臂试验表明在患者经过化疗后用IO102治疗非小细胞肺癌患者可增加患者的无进展生存期(PFS)。

        研究人员采用随机、双盲II期临床试验，用于评估IO102与PD-1单克隆抗体联合治疗对局部晚期或/和转移性NSCLC III-IV 期患者的安全性和有效性。所有的患者均接受化疗为一线治疗方式 。随机将联合治疗作为二线的治疗方式。所有患者随机分组(2：1)至PD-1抑制剂+IO201疫苗或PD-1抑制剂(SOC)治疗。PD-1抑制剂按照要求进行服用，IO102则进行皮下注射，在治疗的前12周每2周注射一次，随后每4周/次治疗一年，或肿瘤发生进展、死亡或者退出试验为止。主要纳入标准是根据RECIST (1.1)诊断为局部晚期和/或转移性NSCLC III期IV期患者，经过化疗后且符合PD-1单克隆抗体治疗的患者，其ECOG赋分0或1，可获取到的肿瘤组织可用于进一步的分析。试验共纳入了90例患者，研究结果将在第二季度欧洲或者美国的相关会议上进行公布。

        编号#TPS2610

        摘要原文：

        Author(s): Anders Mellemgaard, Lotte engel-Norregaard, Mads Hald Andersen, Mai-Britt Zocca, inge Marie Svane; Herlev University Hospital, Herlev, Denmark; Center for Cancer Immune Therapy, Copenhagen, Denmark; IO Biotech, Copenhagen, Denmark

        Background: Multible checkpoints regulate host immune response, and development has focused on three of these: IDO, CTLA-4 and PD-1. Presently, several checkpoint inhibitors have been approved for advanced NSCLC including nivolumab, pembrolizumab, and atezolizumab all targeting PD-1 and PD-L1. Depending on level of PD-L1 tumor expression, response rates vary, and a substantial proportion of patients do not respond to treatment with immune checkpoint inhibitors. The combination of checkpoint inhibitors have been shown in malignant melanoma and other tumor types to clearly increase the effect. IO102 is a synthetic peptide under development as an immune-modulatory agent targeting cells expressing indoleamine 2,3-dioxygenase (IDO). IDO potently inhibits T-cell immunity in patients with cancer. Treatment with IO102 in NSCLC patients after first line palliative chemotherapy lead to long PFS in a number of patients in a small single arm study. Methods: IO102-001 is a randomized, double-blinded Phase 2 trial to evaluate the safety and efficacy of IO102 in combination with anti-PD-1 mAb in locally advanced and/or metastatic NSCLC stage III-IV patients eligible for anti-PD-1 mAb 2nd line treatment after first line of chemotherapy. Patients are randomized (2:1) to either a PD-1 inhibitor + IO201 vaccine or a PD-1 inhibitor (SOC). The PD-1 inhibitor will be administered according to label while IO102 will be given as s.c. injection every 2 weeks for the first 12 weeks, and subsequently every 4 weeks for 12 months or until progression, death or withdrawal from trial, whichever comes first. Treatment is continued to progression, unacceptable toxicity or withdrawal of consent. Main inclusion criteria is patients diagnosed with locally advanced and/or metastatic NSCLC Stage III-IV, measurable disease according to RECIST (1.1), patients eligible for anti PD-1 mAb treatment after 1st line of chemotherapy , ECOG performance status 0 or 1 and available tumor tissue for further analysis. A total of 90 patients will be included in the trial, and the trial will be active in countries in Europe and the US from Q2 2017.