Nivolumab和ipilimumab的联合应用已经被批准用于多种实体瘤的治疗。该研究是一项I期临床试验，调查了nivolumab和ipilimumab用于局部晚期鳞状细胞头颈癌（SCCHN）的确切放射免疫治疗（RIT）。符合顺铂基化疗资格的新诊断IVA-IVB期SCCHN患者在放疗开始前两周开始接受nivolumab（每2周3mg/kg一共17次）和ipilimumab（每6周1mg/kg一共6次）。主要终点为确切RIT的安全性。次要终点包括无进展生存期（PFS）和总生存期（OS）。探索性终点包括基线程序性死亡配体-1（PD-L1）表达及治疗过程中免疫偏倚的相关性与治疗结果。共有24名患者入组。随访中位数为36.1个月，有21名患者（88%）报告了3级或更高与治疗有关的不良事件；5名患者在巩固性免疫治疗过程中出现了现场软组织溃疡，并导致一例死亡。3年PFS为74%（95% CI 58%至94%），OS为96%（95% CI 88%至100%）。PD-L1联合阳性分数（CPS）与死亡或疾病进展无相关性。联合RIT期间细胞外囊泡PD-L1的减少与PFS延长相关（p=0.006）。此外，联合RIT期间循环IL4、IL9、IL12和IL17a的减少与随后的溃疡相关。nivolumab和ipilimumab的确切RIT具有足够的临床活性，支持进一步开发。早期循环生物标志物的变化似乎能够预测治疗结果以及随后的现场软组织溃疡。NCT03162731. © 作者（或其雇主）2023。在CC BY-NC下允许再次使用。不得进行商业再利用。BMJ发布。

The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline programmed death-ligand 1 (PD-L1) expression as well as on-treatment changes in immune bias with treatment outcomes.Twenty-four patients were enrolled. With a median follow-up of 36.1 months, grade 3 or higher treatment-related adverse events were reported in 21 individuals (88%); 5 individuals developed in-field soft tissue ulceration during consolidation immunotherapy, resulting in one fatality. The 3-year PFS and OS rates were 74% (95% CI 58% to 94%) and 96% (95% CI 88% to 100%), respectively. PD-L1 combined positive score (CPS) did not correlate with death or disease progression. Decreases in extracellular vesicle PD-L1 within the concurrent RIT phase were associated with prolonged PFS (p=0.006). Also, interval decreases in circulating interleukin (IL)4, IL9, IL12, and IL17a during concurrent RIT were associated with subsequent ulceration.Definitive RIT with nivolumab and ipilimumab has sufficient clinical activity to support further development. Early changes in circulating biomarkers appear able to predict treatment outcomes as well as ensuing in-field soft tissue ulceration.NCT03162731.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.