在小儿中枢神经系统恶性肿瘤的治疗选择有限。CheckMate 908（NCT03130959）是一个开放标签的连续分支1b/2期研究，旨在调查诺伐普（NIVO）和NIVO+伊匹单抗（IPI）在高级别中枢神经系统恶性肿瘤小儿患者中的应用。在5个队列的166个患者中，采用NIVO 3mg/kg每两周一次（Q2W）或NIVO 3mg/kg+IPI 1mg/kg每三周（4次）后紧接着NIVO 3mg/kg Q2W。主要终点涵盖了总体生存率（新诊断的弥漫性桥脑胶质母细胞瘤[DIPG]）和无进展生存期（PFS；其他复发/进行性或复发/抗药的中枢神经系统队列）。次要终点包括其他疗效指标和安全性。探索性终点包括药代动力学和生物标记物分析。截至2021年1月13日，在新诊断的DIPG中，NIVO和NIVO+IPI的中位OS（80% CI）分别为11.7（10.3-16.5）和10.8（9.1-15.8）个月。在复发/进行性高级别胶质瘤中，NIVO和NIVO+IPI的中位PFS（80% CI）分别为1.7（1.4-2.7）和1.3（1.2-1.5）个月；在复发/抗药的髓母细胞瘤中，分别为1.4（1.2-1.4）和2.8（1.5-4.5）个月；在复发/抗药的室管膜瘤中，分别为1.4（1.4-2.6）和4.6（1.4-5.4）个月。在其他复发/进行性中枢神经系统肿瘤患者中，中位PFS（95% CI）分别为1.2（1.1-1.3）和1.6（1.3-3.5）个月。3/4级治疗相关的不良事件率分别为14.1%（NIVO）和27.2%（NIVO+IPI）。在年龄最小且体重最轻的患者中，NIVO和IPI首次给药的梯度浓度较低。肿瘤程序性死亡配体1表达的基线与生存率无关。NIVO±IPI相对于历史数据没有表现出临床益处，整体安全剖面管理良好，没有新的安全信号。© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO+ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies.Patients (N=166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg+IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts). Secondary endpoints included other efficacy metrics and safety. Exploratory endpoints included pharmacokinetics and biomarker analyses.As of January 13, 2021, median OS (80% CI) was 11.7 (10.3-16.5) and 10.8 (9.1-15.8) months with NIVO and NIVO+IPI, respectively, in newly diagnosed DIPG. Median PFS (80% CI) with NIVO and NIVO+IPI was 1.7 (1.4-2.7) and 1.3 (1.2-1.5) months, respectively, in recurrent/progressive high-grade glioma; 1.4 (1.2-1.4) and 2.8 (1.5-4.5) months in relapsed/resistant medulloblastoma; and 1.4 (1.4-2.6) and 4.6 (1.4-5.4) months in relapsed/resistant ependymoma. In patients with other recurrent/progressive CNS tumors, median PFS (95% CI) was 1.2 (1.1-1.3) and 1.6 (1.3-3.5) months, respectively. Grade 3/4 treatment-related adverse-event rates were 14.1% (NIVO) and 27.2% (NIVO+IPI). NIVO and IPI first-dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor programmed death ligand 1 expression was not associated with survival.NIVO±IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.