抗程序性细胞死亡 1 (PD-1) 免疫疗法是转移性 NSCLC 的标准治疗方法，但许多肿瘤会产生耐药性。我们假设将 T 细胞激动剂（例如 varlilumab（抗 CD27 抗体））与检查点抑制相结合可能会产生协同作用，并且通过使用靶向放射 (RT) 可能会进一步增强这种协同作用。我们进行了一项开放标签、单中心、 I 期试验 (NCT04081688) 旨在确定 atezolizumab 和 varlilumab 联合姑息性放疗治疗经先前程序性细胞死亡配体 1 疗法进展的晚期或转移性 NSCLC 患者的安全性和临床益处。在每个 21 天周期的第一天，患者接受 varlilumab，然后在第 2 天接受 atezolizumab。在第 1 周期和第 2 周期之间对肺部病变进行放疗。总共有 15 名患者入组（一名患者未开始治疗）。中位年龄为 64 岁； 10名患者为女性。 8 名患者 (57%) 患有至少一种治疗相关不良事件 (AE)，7 名患者 (50%) 患有至少一种 III 级或更严重的治疗相关不良事件。只有一种 III 级免疫相关 AE 需要类固醇（1 种腹泻和结肠炎）；没有与治疗相关的死亡。在可评估疗效的 12 名患者中，3 名患者疾病稳定（2 名患者疾病稳定 > 4 个月），临床获益率为 25%。中位无进展生存期为两个月，中位总生存期为 6.4 个月。Varlilumab 与 atezolizumab 和 RT 联合使用是安全且耐受性良好的；没有发现额外的毒性信号。该组合的临床活性适中，25% 的疾病稳定患者为最佳反应。© 2024 作者。

Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.© 2024 The Authors.