IDO1是一种干扰素诱导酶，贡献于肿瘤免疫不耐受。免疫检查点抑制可能会增加干扰素水平；将IDO1抑制与免疫检查点阻断结合使用是一种有吸引力的策略。表观遗传学药物可触发干扰素反应，并可作为免疫疗法激活方法。我们评估了表观遗传学疗法加IDO1抑制和免疫检查点阻断是否对晚期实体瘤患者产生临床益处。ECHO-206是一项I/II期研究，治疗经验丰富的晚期实体肿瘤患者（N = 70）接受了氮芥呋喃核苷加免疫疗法双联用药（依帕酰胺酶1[IDO1抑制剂]和帕博利注射液）。还评估了治疗的顺序。主要终点为安全/耐受性（I期）、最大耐受剂量（MTD）或药效剂量（PAD；I期）以及研究者评估的客观缓解率（ORR；II期）。I期未报告任何剂量限制毒性，未达到MTD；未确定PAD。ORR为5.7％，有4个部分缓解反应。治疗相关的最常见不良事件（AE）为疲劳（42.9％）和恶心（42.9％）。12例（17.1％）患者经历了≥1个致命的AE，其中之一（虚弱感）与治疗有关。虽然氮芥-依帕酰胺酶1-帕博利注射液方案耐受性良好，但在曾接受免疫疗法的晚期实体瘤患者中并未与明显的临床反应相关。 ©2023。作者。

Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors.ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary endpoints were safety/tolerability (Phase I), maximum tolerated dose (MTD) or pharmacologically active dose (PAD; Phase I), and investigator-assessed objective response rate (ORR; Phase II).In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) was treatment-related.Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy.© 2023. The Author(s).