这个I期研究的主要目的是研究在非小细胞肺癌（NSCLC）患者中，主要肿瘤联合双重免疫检查点抑制（SICI）的立体定向放疗的安全性和耐受性。通过放射治疗增加新抗原的释放可能会增强免疫治疗的反应，特别是通过针对主要肿瘤的核心突变。在三个连续的队列中，研究了结合立体定向体放疗（SBRT ）对主要肿瘤（9 cc上的1x20 Gy ）的免疫治疗方案，以治疗III B / IV NSCLC患者在化疗中进展的情况。第一队（n = 3）接受durvalumab。第二队（n = 6）接受tremelimumab 和 durvalumab 的联合，并随后接受durvalumab 单独治疗。第三个队（n = 6）类似，但组合反转。使用描述性统计学来评估安全参数和有效性的探索性结果。不良事件使用NCI CTCAE 版本4.03 汇报。基线时分析呼气气息。共纳入了15名患者，中位数照射体积为 9.13 cc，中位数原发肿瘤体积为79 cc。有7名患者出现1-2级别的治疗相关不良事件，有2名患者出现3级别的治疗相关不良事件。双重免疫疗法有1例限制剂毒性（结肠炎）。结合SBRT对主要肿瘤和双重免疫治疗在晚期NSCLC患者中是安全和可行的。版权所有©2023，由Elsevier B.V.出版。

This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor.In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline.Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1-2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy.The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible.Copyright © 2023. Published by Elsevier B.V.