Evidence map›Paper›PMID 36808285›Full record

Trial reportNeuro-oncology2023

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 and 9 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03130959 (Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies), which is not on this map. Cited by 48 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 4 pooled it
15.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03130959 phase2completednot on this map

Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies

TypeinterventionalSponsorBristol-Myers SquibbRan2017 to 2022Enrolled166ConditionsVarious Advanced CancerArmsNivolumab, Ipilimumab
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 4 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Review
  6. From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
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  13. Article
  14. Review
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  19. Article
  20. Ependymoma: Advances in Systems Treatment Strategies.Current neurology and neuroscience reports · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 14 institutions in 7 countries.

Ira J DunkelDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0001-8091-6067
François DozSIREDO Center, Institut Curie and University Paris Cité, Paris, France.
Nicholas K ForemanMorgan Adams Foundation Pediatric Brain Tumor Research Program, Children's Hospital Colorado, Aurora, Colorado, USA.
Darren HargraveGreat Ormond Street Hospital for Children, London, UK.
Alvaro LassalettaDepartment of Pediatric Hematology-Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Nicolas AndréDépartement de Radiothérapie, Hopital pour Enfants de la Timone, Department of Pediatric Hematology and Oncology, AP-HM and Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.
Jordan R HansfordChildren's Cancer Centre, Royal Children's Hospital, Murdoch Children's Research Institute, Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Tim HassallQueensland Children's Hospital, Oncology Services Group, South Brisbane, Queensland, Australia.
Matthias EyrichDepartment of Pediatric Hematology, Oncology and Stem Cell Transplantation, Universitätsklinikum Würzburg, Würzburg, Germany.
Sridharan GururanganDepartment of Pediatrics, Preston A. Wells Center for Brain Tumor Therapy, Gainesville, Florida, USA.
Ute BartelsDepartment of Hematology and Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID 0000-0003-2112-5251
Amar GajjarDepartment of Oncology, St. Jude's Children's Hospital, Memphis, Tennessee, USA.
Lisa HowellPediatric Oncology, Alder Hey Children's Hospital, Liverpool, UK.
Deepti WaradBristol Myers Squibb, Princeton, New Jersey, USA.
Misena PaciusBristol Myers Squibb, Princeton, New Jersey, USA.
Rachel TamBristol Myers Squibb, Princeton, New Jersey, USA.
Yu WangBristol Myers Squibb, Princeton, New Jersey, USA.
Li ZhuBristol Myers Squibb, Princeton, New Jersey, USA.
Kenneth CohenDivision of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Bristol-Myers Squibb (United States) · USAix-Marseille Université · FRChildren's Health Queensland Hospital and Health Service · AUGreat Ormond Street Hospital · GBHospital for Sick Children · CAHospital Infantil Universitario Niño Jesús · ESJohns Hopkins Hospital · USMemorial Sloan Kettering Cancer Center · USMorgan Adams Foundation · USRoyal Children's Hospital · AUSt. Jude Children's Research Hospital · USUniversitätsklinikum Würzburg · DEUniversité Paris Cité · FRUniversity of Liverpool · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
Department of HealthNCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundTherapeutic 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.

methodsPatients (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.

resultsAs 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.

conclusionsNIVO ± IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals.

Indexed as

NeoplasmsNivolumabAntineoplastic Combined Chemotherapy ProtocolsBiomarkersChildHumansIpilimumabBiomarkersIpilimumabNivolumabcheckpoint inhibitorsDIPGependymomaHGGmedulloblastoma

Identifiers

PMID36808285
PMCPMC10398811
OpenAlexW4321372568

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.