# Neoadjuvant immunotherapy with surgical window for glioblastoma

Source: https://onco.cc/ideas/idea-neoadjuvant-io-glioblastoma/  
OnCo record `idea-neoadjuvant-io-glioblastoma` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-06
- 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.
- Proposed 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

## Sources

- ClinicalTrials.gov NCT02667587: CheckMate 548: https://clinicaltrials.gov/study/NCT02667587
- ClinicalTrials.gov NCT02017717: CheckMate 143: https://clinicaltrials.gov/study/NCT02017717
- ClinicalTrials.gov NCT02617589: CheckMate 498: https://clinicaltrials.gov/study/NCT02617589

## Connected records

- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- technologies: [CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)](https://onco.cc/technologies/glioma-car-t/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- trials: [CheckMate 143](https://onco.cc/trials/checkmate-143/), [CheckMate 498](https://onco.cc/trials/checkmate-498/), [CheckMate 548](https://onco.cc/trials/checkmate-548/)
- key papers: [Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study](https://onco.cc/key-papers/paper-pembrolizumab-glioblastoma-med-2025/), [Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma](https://onco.cc/key-papers/paper-pembrolizumab-glioblastoma-clin-cancer-res-2021/), [Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma](https://onco.cc/key-papers/paper-pembrolizumab-glioblastoma-clin-cancer-res-2025/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)

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