# Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study

Source: https://onco.cc/key-papers/paper-pembrolizumab-glioblastoma-med-2025/  
OnCo record `paper-pembrolizumab-glioblastoma-med-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Phase 2 or 3 results paper on Pembrolizumab in Glioma & glioblastoma, in Med (New York, N.Y.) (2025), one of the most cited Europe PMC records with Pembrolizumab in its title.

## Summary

Background: Immune checkpoint inhibitors (ICIs) have shown limited success in glioblastoma due to the tumor's profoundly immunosuppressive microenvironment. Tumor treating fields (TTFields), a non-invasive electric field therapy, activate the type I interferon (T1IFN) pathway via DNA sensor-dependent inflammasomes, promoting in situ immunization against glioblastoma.

Methods: In this phase 2 study (this study was registered at ClinicalTrials.gov: NCT03405792), 31 newly diagnosed glioblastoma patients were enrolled post-chemoradiation to evaluate synergy between TTFields, pembrolizumab, and temozolomide. The primary endpoint was progression-free survival (PFS) compared to case-matched controls treated with TTFields and temozolomide alone. Secondary endpoints included overall survival (OS), response rate, safety, and immune correlates assessed through single-cell transcriptomics and T cell clonotyping of blood and tumor samples.

Findings: Among 26 patients treated per protocol, the median PFS was 12.0 vs. 5.8 months in controls (HR 0.377, 95% CI 0.217-0.653; p = 0.0026), and the median OS was 24.8 vs. 14.6 months (HR 0.522, 95% CI 0.301-0.905; p = 0.0477). Patients undergoing biopsy had longer PFS (27.2 vs. 9.6 months; HR 0.37, 95% CI 0.16-0.85; p = 0.014) and OS (31.6 vs. 18.8 months; HR 0.4, 95% CI 0.17-0.92; p = 0.023) compared to maximal resection. Severe adverse events constituted 7.5% of treatment-related toxicities. TTFields promoted clonal T cell expansion via a T1IFN-driven trajectory, while pembrolizumab supported adaptive replacement of these clones, sustaining T cell activation and memory formation, especially in biopsy-only patients.

Conclusions: These findings demonstrate synergy between TTFields and ICIs, particularly in patients with high tumor burden, and support further study in larger trials.

Funding: This work was supported by a grant from Novocure.

Indexed on Europe PMC as PubMed record 40466642 (DOI 10.1016/j.medj.2025.100708). Its title names Pembrolizumab and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't). It was matched automatically to the idea "Neoadjuvant immunotherapy with surgical window for glioblastoma" and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Med (New York, N.Y.)
- Year: 2025
- DOI: 10.1016/j.medj.2025.100708
- Authors: Chen D, Le SB, Ghiaseddin AP, et al.
- What it means: One of the most cited trial reports Europe PMC returns for Pembrolizumab in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by Pembrolizumab in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.

## Sources

- Med 2025: https://doi.org/10.1016/j.medj.2025.100708
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40466642/
- Europe PMC: https://europepmc.org/article/MED/40466642

## Connected records

- ideas: [Neoadjuvant immunotherapy with surgical window for glioblastoma](https://onco.cc/ideas/idea-neoadjuvant-io-glioblastoma/)

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