唾液腺癌（SGCs）是罕见而具侵袭性的癌症，转移后缺乏有效的治疗方法。我们进行了一项第2期试验，评估了尼伐替尼（尼，抗PD-1）和伊匹利姆（伊，抗CTLA-4）在64名晚期SGC患者中的疗效，这些患者分为两个基于组织学的队列（每个队列32名患者）：腺样囊性癌（ACC；队列1）和其他SGC（队列2）。组2（5/32，16%）达到了主要疗效终点（≥4个客观反应），而组1（2/32，6%）未能达到。治疗相关的不良事件≥3级发生在64名患者中的24例（38%），两个队列的中位无进展生存期（PFS）分别为4.4个月（95%置信区间（CI）：2.4，8.3）和2.2个月（95% CI：1.8，5.3）。我们提供了来自术前和术中肿瘤的全外显子、RNA和TCR测序数据，以及来自序列时间点的外周血液的免疫细胞流式细胞术和TCR测序。反应性肿瘤普遍显示了既往存在的T细胞的克隆扩张和突变收缩。反应性的ACC携带有诱导外体T细胞反应的新抗原，包括融合源新表位。本研究显示，尼+伊对ACC的疗效有限，尽管罕见，但有异常的反应，并且可能对非ACC SGCs，特别是涎管癌具有潜力。 ClinicalTrials.gov标识符：NCT03172624。© 2023 The Author(s),在Springer Nature America, Inc.的独家许可下。

Salivary gland cancers (SGCs) are rare, aggressive cancers without effective treatments when metastasized. We conducted a phase 2 trial evaluating nivolumab (nivo, anti-PD-1) and ipilimumab (ipi, anti-CTLA-4) in 64 patients with metastatic SGC enrolled in two histology-based cohorts (32 patients each): adenoid cystic carcinoma (ACC; cohort 1) and other SGCs (cohort 2). The primary efficacy endpoint (≥4 objective responses) was met in cohort 2 (5/32, 16%) but not in cohort 1 (2/32, 6%). Treatment safety/tolerability and progression-free survival (PFS) were secondary endpoints. Treatment-related adverse events grade ≥3 occurred in 24 of 64 (38%) patients across both cohorts, and median PFS was 4.4 months (95% confidence interval (CI): 2.4, 8.3) and 2.2 months (95% CI: 1.8, 5.3) for cohorts 1 and 2, respectively. We present whole-exome, RNA and T cell receptor (TCR) sequencing data from pre-treatment and on-treatment tumors and immune cell flow cytometry and TCR sequencing from peripheral blood at serial timepoints. Responding tumors universally demonstrated clonal expansion of pre-existing T cells and mutational contraction. Responding ACCs harbored neoantigens, including fusion-derived neoepitopes, that induced T cell responses ex vivo. This study shows that nivo+ipi has limited efficacy in ACC, albeit with infrequent, exceptional responses, and that it could be promising for non-ACC SGCs, particularly salivary duct carcinomas. ClinicalTrials.gov identifier: NCT03172624 .© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.