{"doi":"10.1093/neuonc/noad031","title":"Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics—CheckMate 908","abstract":"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.","journal":"Neuro-Oncology","year":2023,"id":318365,"datarank":1.2678235836649832,"base_score":4.189654742026425,"endowment":4.189654742026425,"self_citation_contribution":0.6284482113039639,"citation_network_contribution":0.6393753723610193,"self_endowment_contribution":0.6284482113039639,"citer_contribution":0.6393753723610193,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":58,"citers_with_citation_signal":42,"citers_with_endowment":42,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9441,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03130959"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":638255,"name":"François Doz","orcid":"0000-0001-9286-4831","position":1,"is_corresponding":false},{"id":132351,"name":"Nicholas K. Foreman","orcid":"0000-0003-4848-4801","position":2,"is_corresponding":false},{"id":65274,"name":"Darren Hargrave","orcid":"0000-0001-8219-9807","position":3,"is_corresponding":false},{"id":607792,"name":"Álvaro Lassaletta","orcid":"0000-0003-2881-1473","position":4,"is_corresponding":false},{"id":841355,"name":"Nicolás André","orcid":"0000-0002-6786-4968","position":5,"is_corresponding":false},{"id":246738,"name":"Jordan R. Hansford","orcid":"0000-0001-7733-383X","position":6,"is_corresponding":false},{"id":236634,"name":"Tim Hassall","orcid":"0000-0002-7883-3710","position":7,"is_corresponding":false},{"id":620960,"name":"Matthias Eyrich","orcid":"0000-0002-8099-5903","position":8,"is_corresponding":false},{"id":568974,"name":"Sridharan Gururangan","orcid":"0000-0003-0311-7127","position":9,"is_corresponding":false},{"id":351811,"name":"Ute Bartels","orcid":"0000-0003-2112-5251","position":10,"is_corresponding":false},{"id":5546,"name":"Amar Gajjar","orcid":"0000-0001-5019-0699","position":11,"is_corresponding":false},{"id":1025547,"name":"Lisa Howell","orcid":"0000-0003-2119-2630","position":12,"is_corresponding":false},{"id":545890,"name":"Deepti Warad","orcid":"0000-0002-1899-5208","position":13,"is_corresponding":false},{"id":1026181,"name":"Misena Pacius","orcid":null,"position":14,"is_corresponding":false},{"id":1025548,"name":"Rachel Tam","orcid":"0009-0009-8556-1109","position":15,"is_corresponding":false},{"id":964075,"name":"Yu Wang","orcid":"0000-0002-0934-8826","position":16,"is_corresponding":false},{"id":1025549,"name":"Li Zhu","orcid":"0000-0002-7804-907X","position":17,"is_corresponding":false},{"id":1025550,"name":"Kenneth J. Cohen","orcid":"0000-0001-9193-9344","position":18,"is_corresponding":false},{"id":236601,"name":"Ira J. Dunkel","orcid":"0000-0001-8091-6067","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"36808285","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}