Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3‐dioxygenase 1 (IDO1). Here we report results from the open‐label, dose‐escalation, Phase 1b ECHO‐110 study evaluating epacadostat plus atezolizumab in patients with previously treated Stage IIIB/IV nonsmall cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum‐based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment. Oral epacadostat (25, 50, 75, 100, 200 or 300 mg) was administered twice daily (BID) with intravenous atezolizumab 1,200 mg every 3 weeks (Q3W). Primary endpoints were safety, tolerability and dose‐limiting toxicities (DLTs). Twenty‐nine patients received ≥1 dose of treatment. The maximum tolerated dose of epacadostat was not reached. Two patients had DLTs: one patient with Grade 3 dehydration and hypotension (epacadostat 200 mg BID); one patient with Grade 3 hyponatremia and Grade 4 autoimmune encephalitis (epacadostat 300 mg BID). Twenty‐three patients (79%) had treatment‐related adverse events (AEs); seven patients (24%) experienced Grade 3/4 events; five patients (17%) discontinued treatment due to treatment‐related AEs. No fatal treatment‐related AEs occurred. One patient achieved a partial response (objective response rate, 3%), which was maintained for 8.3 months; eight patients had stable disease. Baseline tumoral programmed cell death ligand 1 (PD‐L1) and IDO expression were low among patients with evaluable samples (1 of 23 expressed PD‐L1; 5 of 17 expressed IDO). Epacadostat pharmacokinetics was comparable to historical controls. Epacadostat, at doses up to 300 mg BID, combined with atezolizumab 1,200 mg Q3W was well tolerated in patients with previously treated NSCLC, although clinical activity was limited.

中文翻译：

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epacadostat 联合 atezolizumab 用于先前治疗的晚期非小细胞肺癌患者的 1 期研究。

Epacadostat 是一种有效且高度选择性的吲哚胺 2,3-双加氧酶 1 (IDO1) 抑制剂。在这里，我们报告了开放标签、剂量递增、1b 期 ECHO-110 研究的结果，该研究评估了先前治疗过的 IIIB/IV 期非小细胞肺癌 (NSCLC) 患者中的 epacadostat 加 atezolizumab。符合条件的患者既往接受过≥1 次铂类化疗（≥2 个周期）且未接受过检查点/IDO 抑制剂治疗。每天两次 (BID) 口服 epacadostat（25、50、75、100、200 或 300 mg），每 3 周（Q3W）静脉注射 1,200 mg 阿特珠单抗。主要终点是安全性、耐受性和剂量限制性毒性 (DLT)。29 名患者接受了≥1 剂的治疗。未达到 epacadostat 的最大耐受剂量。两名患者患有 DLT：一名患有 3 级脱水和低血压的患者（epacadostat 200 mg BID）；一名患有 3 级低钠血症和 4 级自身免疫性脑炎的患者（epacadostat 300 mg BID）。23 名患者 (79%) 出现与治疗相关的不良事件 (AE)；7 名患者 (24%) 经历了 3/4 级事件；5 名患者 (17%) 由于治疗相关的 AE 停止治疗。没有发生致命的治疗相关 AE。1 例患者达到部分缓解（客观缓解率，3%），并维持 8.3 个月；8名患者病情稳定。在具有可评估样本的患者中，基线肿瘤程序性细胞死亡配体 1 (PD-L1) 和 IDO 表达较低（23 人中有 1 人表达 PD-L1；17 人中有 5 人表达 IDO）。Epacadostat 的药代动力学与历史对照相当。Epacadostat，剂量高达 300 mg BID，