Evidence map›Paper›PMID 40016450›Full record

ArticleNature medicine2025

Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma.

Georgina V Long, Elena Shklovskaya, Laveniya Satgunaseelan, Yizhe Mao, Inês Pires da Silva, Kristen A Perry, Russell J Diefenbach, Tuba N Gide, Brindha Shivalingam, Michael E Buckland and 25 more

Registry-linked trialAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06816927 (A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab), which is not on this map. Cited by 53 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06816927 phase2recruitingnot on this map

A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (GIANT)

TypeinterventionalSponsorDuke UniversityRan2025 to 2031Enrolled92ConditionsNewly Diagnosed GlioblastomaArmsNivolumab, Relatlimab, TMZ, Radiation Therapy
3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Phase I Evaluation of Patients with Newly Diagnosed Glioblastoma Treated with Radiation, Nivolumab, and IDO1 Enzyme Inhibitor BMS-986205.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  7. Article
  8. Article
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  10. Advances and challenges in glioblastoma immunotherapy: a meta-analysis of immune checkpoint inhibitors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  11. Article
  12. Immune Subtypes and Survival in Patients with Primary Glioma.medRxiv : the preprint server for health sciences · 2026
    Article
  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Georgina V LongMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia. georgina.long@sydney.edu.au.ORCID http://orcid.org/0000-0001-8894-3545
Elena ShklovskayaMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-6155-1020
Laveniya SatgunaseelanFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7435-0834
Yizhe MaoMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1863-512X
Inês Pires da SilvaMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Kristen A PerryMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Russell J DiefenbachMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-8433-4336
Tuba N GideMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Brindha ShivalingamMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Michael E BucklandFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Maria GonzalezMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-2197-6657
Nicole CaixeiroMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Ismael A VergaraMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Xinyu BaiMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Robert V RawsonMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Edward HsiaoMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Umaimainthan PalendiraFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Tri Giang PhanFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4909-2984
Alexander M MenziesMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Matteo S CarlinoMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Camelia QuekMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-1244-961X
Sean M GrimmondCollaborative Centre for Genomic Cancer Medicine, University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-8102-7998
Joseph H A VissersCollaborative Centre for Genomic Cancer Medicine, University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0003-0435-6824
Dannel YeoFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
John E J RaskoFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-3181-7198
Mustafa KhasrawDuke University, Durham, NC, USA.ORCID http://orcid.org/0000-0003-3249-9849
Bart NeynsUniversitair Ziekenhuis Brussel, Brussels, Belgium.
David A ReardonCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6674-0157
David M AshleyDuke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-4754-5900
Helen WheelerRoyal North Shore Hospital, St Leonards, New South Wales, Australia.
Michael BackRoyal North Shore Hospital, St Leonards, New South Wales, Australia.
Richard A ScolyerMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-8991-0013
James DrummondRoyal North Shore Hospital, St Leonards, New South Wales, Australia.
James S WilmottMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.
Helen RizosMelanoma Institute Australia, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-2094-9198

Funding

Cancer Institute NSW (Cancer Institute New South Wales) 2020/ECF1153Cancer Institute NSW (Cancer Institute New South Wales) 2020/ECF1244Cancer Institute NSW (Cancer Institute New South Wales) 2021/CBG0002
6 · The paper itself

Abstract

Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma brain metastases, they have shown limited efficacy in patients with resected or recurrent GBM. The lack of efficacy has been attributed to the scarcity of tumor-infiltrating lymphocytes (TILs), an immunosuppressive tumor microenvironment and low tumor mutation burden typical of GBM tumors, plus exclusion of large molecules from the brain parenchyma. We hypothesized that upfront neoadjuvant combination immunotherapy, administered with disease in situ, could induce a stronger immune response than treatment given after resection or after recurrence. Here, we present a case of newly diagnosed IDH-wild-type, MGMT promoter unmethylated GBM, treated with a single dose of neoadjuvant triplet immunotherapy (anti-programmed cell death protein 1 plus anti-cytotoxic T-lymphocyte protein 4 plus anti-lymphocyte-activation gene 3) followed by maximal safe resection 12 days later. The anti-programmed cell death protein 1 drug was bound to TILs in the resected GBM and there was marked TIL infiltration and activation compared with the baseline biopsy. After 17 months, there is no definitive sign of recurrence. If used first line, before safe maximal resection, checkpoint inhibitors are capable of immune activation in GBM and may induce a response. A clinical trial of first-line neoadjuvant combination checkpoint inhibitor therapy in newly diagnosed GBM is planned (GIANT; trial registration no. NCT06816927 ).

Indexed as

Brain NeoplasmsGlioblastomaImmune Checkpoint InhibitorsNeoadjuvant TherapyHumansImmunotherapyLymphocytes, Tumor-InfiltratingProgrammed Cell Death 1 ReceptorTumor MicroenvironmentImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID40016450
PMCPMC12092302

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.