{"entity":{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","aka":[],"tldr":"Give immunotherapy before surgery rather than after, so the tumour is still present to teach the immune system, then look inside it to learn what happened.","summary":"A Nature Medicine 2019 study by Cloughesy and colleagues showed that neoadjuvant pembrolizumab in recurrent glioblastoma increased interferon signatures and T-cell clonal expansion and was associated with longer OS than adjuvant-only in a small randomised study, the only positive checkpoint signal in the disease. Window-of-opportunity designs (GESTALT, ASCO 2026) show feasibility.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02667587: CheckMate 548","url":"https://clinicaltrials.gov/study/NCT02667587"},{"label":"ClinicalTrials.gov NCT02017717: CheckMate 143","url":"https://clinicaltrials.gov/study/NCT02017717"},{"label":"ClinicalTrials.gov NCT02617589: CheckMate 498","url":"https://clinicaltrials.gov/study/NCT02617589"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["checkpoint-inhibitor","glioma-car-t"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","cold-vs-hot"],"trials":["checkmate-143","checkmate-498","checkmate-548"],"people":[],"bottlenecks":[],"keyPapers":["paper-pembrolizumab-glioblastoma-clin-cancer-res-2021","paper-pembrolizumab-glioblastoma-med-2025","paper-pembrolizumab-glioblastoma-clin-cancer-res-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant PD-1 blockade ± vaccine or CAR-T, with steroid minimisation, improves OS in recurrent glioblastoma compared with adjuvant-only administration.","rationale":"Antigen supply from intact tumour, tissue-based pharmacodynamic read-outs, and avoidance of post-operative lymphopenia and dexamethasone.","test":"Randomised phase 2 neoadjuvant-plus-adjuvant versus adjuvant-only PD-1 in resectable recurrent GBM with mandated steroid protocols; OS primary, tissue immune correlates secondary.","maturity":"early-clinical"},"route":"/ideas/idea-neoadjuvant-io-glioblastoma/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"technology":[{"id":"glioma-car-t","kind":"technology","name":"CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)","route":"/technologies/glioma-car-t/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"trial":[{"id":"checkmate-143","kind":"trial","name":"CheckMate 143","route":"/trials/checkmate-143/"},{"id":"checkmate-498","kind":"trial","name":"CheckMate 498","route":"/trials/checkmate-498/"},{"id":"checkmate-548","kind":"trial","name":"CheckMate 548","route":"/trials/checkmate-548/"}],"paper":[{"id":"paper-pembrolizumab-glioblastoma-med-2025","kind":"paper","name":"Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study","route":"/key-papers/paper-pembrolizumab-glioblastoma-med-2025/"},{"id":"paper-pembrolizumab-glioblastoma-clin-cancer-res-2021","kind":"paper","name":"Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma","route":"/key-papers/paper-pembrolizumab-glioblastoma-clin-cancer-res-2021/"},{"id":"paper-pembrolizumab-glioblastoma-clin-cancer-res-2025","kind":"paper","name":"Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma","route":"/key-papers/paper-pembrolizumab-glioblastoma-clin-cancer-res-2025/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}]}}