{"entity":{"id":"checkmate-548","kind":"trial","name":"CheckMate 548","aka":[],"tldr":"CheckMate 548 added nivolumab to standard radiotherapy and temozolomide in newly diagnosed glioblastoma and found no benefit. With CheckMate 143 and 498 it makes three large negative trials: the immunotherapy that transformed melanoma and lung cancer did nothing in glioblastoma.","summary":"CheckMate 548, trial NCT02667587 sponsored by BMS, randomised 716 patients with newly diagnosed glioblastoma and a methylated MGMT promoter to nivolumab or placebo added to radiotherapy and temozolomide. Median progression-free survival by blinded central review was 10.6 versus 10.3 months and median overall survival 28.9 versus 32.1 months (HR 1.1, 95% CI 0.9-1.3 for both); grade 3/4 treatment-related adverse events were more frequent with nivolumab (52.4% versus 33.6%). Published by Lim and colleagues in Neuro-Oncology (2022;24:1935-1949). Together with CheckMate 143 (recurrent) and CheckMate 498 (MGMT-unmethylated) it completes three negative phase 3 trials of PD-1 blockade in glioblastoma. Explanations: low mutational burden, T-cell exclusion behind the blood-brain barrier, steroid immunosuppression, systemic lymphopenia. Neoadjuvant PD-1 (Cloughesy 2019) showed immune activation and remains the only encouraging signal.","status":"negative","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02667587","url":"https://clinicaltrials.gov/study/NCT02667587"},{"label":"Lim et al., Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter (Neuro-Oncology 2022)","url":"https://doi.org/10.1093/neuonc/noac116"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt"],"targets":["pd1"],"drugs":["nivolumab","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["mgmt","cold-vs-hot","blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lim-neuro-oncol"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02667587","phase":"3","setting":"Newly diagnosed glioblastoma with methylated MGMT promoter: nivolumab vs placebo added to radiotherapy and temozolomide","sponsor":"BMS","result":"OS 28.9 vs 32.1 months, HR 1.1 (95% CI 0.9-1.3); no PFS or OS benefit.","started":"2016-05-09","startedType":"actual","yearReported":2022,"enrolled":716,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, MGMT-methylated glioblastoma","primary":true,"unit":"months","arms":[{"name":"Nivolumab + RT + temozolomide","n":358,"value":28.9,"note":"Not significant"},{"name":"Placebo + RT + temozolomide","n":358,"value":32.1}],"hr":1.1,"ci":[0.92,1.32],"source":"https://doi.org/10.1093/neuonc/noac116"}],"replication":"Consistent with CheckMate 143 and 498: three negative randomised trials of PD-1 blockade in glioblastoma."},"route":"/trials/checkmate-548/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"}],"term":[{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"mgmt","kind":"term","name":"MGMT promoter methylation","route":"/terms/mgmt/"}],"paper":[{"id":"paper-lim-neuro-oncol","kind":"paper","name":"Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter","route":"/key-papers/paper-lim-neuro-oncol/"}],"idea":[{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","route":"/ideas/idea-neoadjuvant-io-glioblastoma/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}]}}