免疫檢查點可以對免疫反應起到調節作用。現在主要的免疫檢查點有IDO、CTLA-4和PD-1。目前，FDA已經批準了幾種治療晚期非小細胞肺癌的免疫檢查點抑製劑，包括靶向PD-1和PD-L1治療的BMS的納武單抗(nivolumab)、MSD的派姆單抗(pembrolizumab)以及羅氏的atezolizumab。患者的治療效果也因PD-L1的表達水平而異，而且相當一部分患者對於這些免疫檢查點抑製劑的治療並不響應。在黑色素瘤和其他腫瘤患者當中限時免疫檢查點抑製劑的聯合療法會增加免疫治療的效果。吲哚胺2,3-雙加氧酶(IDO)是細胞的免疫調節劑，其可以有效抑製癌症患者T細胞的免疫作用。IO102是新開發的一種合成肽，為IDO的抑製劑，一項小型的單臂試驗表明在患者經過化療後用IO102治療非小細胞肺癌患者可增加患者的無進展生存期(PFS)。

研究人員采用隨機、雙盲II期臨床試驗，用於評估IO102與PD-1單克隆抗體聯合治療對局部晚期或/和轉移性NSCLC III-IV 期患者的安全性和有效性。所有的患者均接受化療為一線治療方式 。隨機將聯合治療作為二線的治療方式。所有患者隨機分組(2：1)至PD-1抑製劑+IO201疫苗或PD-1抑製劑(SOC)治療。PD-1抑製劑按照要求進行服用，IO102則進行皮下注射，在治療的前12周每2周注射一次，隨後每4周/次治療一年，或腫瘤發生進展、死亡或者退出試驗為止。主要納入標準是根據RECIST (1.1)診斷為局部晚期和/或轉移性NSCLC III期IV期患者，經過化療後且符合PD-1單克隆抗體治療的患者，其ECOG賦分0或1，可獲取到的腫瘤組織可用於進一步的分析。試驗共納入了90例患者，研究結果將在第二季度歐洲或者美國的相關會議上進行公布。

編號#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.