Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics-CheckMate 908

Ira J. Dunkel, François Doz, Nicholas K. Foreman, Darren Hargrave, Alvaro Lassaletta, Nicolas André, Jordan R. Hansford, Tim Hassall, Matthias Eyrich, Sridharan Gururangan, Ute Bartels, Amar Gajjar, Lisa Howell, Deepti Warad, Misena Pacius, Rachel Tam, Yu Wang, Li Zhu, Kenneth Cohen

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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: NIVO ± IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals.

Original languageEnglish
Pages (from-to)1530-1545
Number of pages16
Issue number8
Early online date20 Feb 2023
Publication statusPublished or Issued - 3 Aug 2023
Externally publishedYes


  • checkpoint inhibitors
  • DIPG
  • ependymoma
  • HGG
  • medulloblastoma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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