ideasIdea
Neoadjuvant immunotherapy with surgical window for glioblastoma
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.
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.
Confidence
10%–25%likelyOnCo editors (initial estimate), 2026-09-07 · Prior IO trials in glioblastoma were negative; neoadjuvant timing is a hypothesis, not a fix.
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.
What would test it
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