Evidence map›Paper›PMID 40120123›Full record

ArticleNeuro-oncology2025

A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma.

Patrick Y Wen, Andrea Manzanera, Caroline Duault, Edgar Gonzalez-Kozlova, Lenika Lopez, Stuart A Grossman, Xiaobu Ye, Joy Fisher, Ian Lee, Tobias Walbert and 45 more

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03576612 (Phase I Study of Neoadjuvant GMCI Plus Immune Checkpoint Inhibitor Combined With Standard of Care for Newly Diagnosed High-Grade Gliomas), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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.

NCT03576612 phase1completednot on this map

Phase I Study of Neoadjuvant GMCI Plus Immune Checkpoint Inhibitor Combined With Standard of Care for Newly Diagnosed High-Grade Gliomas

TypeinterventionalSponsorCandel Therapeutics, Inc.Ran2018 to 2023Enrolled41ConditionsGlioma, MalignantArmsAdV-tk, Valacyclovir, Radiation, Temozolomide, Nivolumab
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. The emerging role of oncolytic virotherapy in genitourinary malignancies.Frontiers in cell and developmental biology · 2026
    Review
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors.

Patrick Y WenAdult Brain Tumor Consortium, Baltimore, Maryland, USA.
Andrea ManzaneraCandel Therapeutics, Needham, Massachusetts, USA.
Caroline DuaultStanford University, Stanford, California, USA.
Edgar Gonzalez-KozlovaMount Sinai, New York, New York, USA.
Lenika LopezCandel Therapeutics, Needham, Massachusetts, USA.
Stuart A GrossmanDepartment of Neurosurgery, Division of Neuro-oncology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.ORCID 0000-0002-3726-7679
Xiaobu YeDepartment of Neurosurgery, Division of Neuro-oncology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.
Joy FisherDepartment of Neurosurgery, Division of Neuro-oncology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.
Ian LeeDepartment of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan, USA.
Tobias WalbertDepartment of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan, USA.ORCID 0000-0003-0667-8106
James SnyderDepartment of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan, USA.
Steven BremDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Arati DesaiDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Stephen J BagleyDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-7117-0539
Chandana KakaniDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Roy StrowdDepartment of Neurosurgery, Wake Forest Health Sciences Center, Salem, North Carolina, USA.
Stephen TatterDepartment of Neurosurgery, Wake Forest Health Sciences Center, Salem, North Carolina, USA.
Adrian LaxtonDepartment of Neurosurgery, Wake Forest Health Sciences Center, Salem, North Carolina, USA.
Glenn LesserDepartment of Neurosurgery, Wake Forest Health Sciences Center, Salem, North Carolina, USA.
Nduka AmankulorDepartment of Neurosurgery, Glioblastoma Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Frank LiebermanHillman Cancer Center, Departments of Neurology and Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA.
Jan DrappatzHillman Cancer Center, Departments of Neurology and Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA.
Megan ManticaHillman Cancer Center, Departments of Neurology and Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA.
Dan TriggsDepartment of Neurosurgery, Brigham and Women's Hospital and Center for Nervous System Tumors, Mass General Brigham, Boston, Massachusetts, USA.
Cara HaymakerDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Gheath Al-AtrashDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Julia Mendoza PerezDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Andrew FutrealDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Latasha D LittleDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
M D Habibul IslamDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Dzifa DuoseDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Peixin JiangDepartment of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
Alexandre ReubenDepartment of Stem Cell Transplantation, MD Anderson Cancer Center, Houston, Texas, USA.
Sean E LawlerStanford University, Stanford, California, USA.
Mina PichavantStanford University, Stanford, California, USA.
Andrew GentlesStanford University, Stanford, California, USA.
Sean BendallStanford University, Stanford, California, USA.
Alex KongStanford University, Stanford, California, USA.
Christine CamachoMount Sinai, New York, New York, USA.
Diane Del ValleMount Sinai, New York, New York, USA.
Seunghee Kim-SchulzeMount Sinai, New York, New York, USA.
Sacha GnjaticDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Elad SharonDepartment of Neurosurgery, Brigham and Women's Hospital and Center for Nervous System Tumors, Mass General Brigham, Boston, Massachusetts, USA.
M Oskar NowickiDepartment of Neurosurgery, Brigham and Women's Hospital and Center for Nervous System Tumors, Mass General Brigham, Boston, Massachusetts, USA.
Pierpaolo PeruzziCandel Therapeutics, Needham, Massachusetts, USA.
Doug LaneCandel Therapeutics, Needham, Massachusetts, USA.
Estuardo Aguilar-CordovaCandel Therapeutics, Needham, Massachusetts, USA.
Laura K AguilarCandel Therapeutics, Needham, Massachusetts, USA.
Garrett NicholsCandel Therapeutics, Needham, Massachusetts, USA.
Jessica DwyerCandel Therapeutics, Needham, Massachusetts, USA.
Paul Peter TakStanford University, Stanford, California, USA.
Holden MaeckerCandel Therapeutics, Needham, Massachusetts, USA.
Francesca BaroneDepartment of Neurosurgery, Brigham and Women's Hospital and Center for Nervous System Tumors, Mass General Brigham, Boston, Massachusetts, USA.
E Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital and Center for Nervous System Tumors, Mass General Brigham, Boston, Massachusetts, USA.ORCID 0000-0001-5183-1670

Funding

Stanford Cancer Immune Monitoring and Analysis Center (CIMAC)U24CA224309 · NCI · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Holden T. Maecker · 2017 to 2026
$19.9M
Translational Cancer Immune Monitoring and Analysis Center (TCIMAC)U24CA224285 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gheath Al-Atrash, Cara L Haymaker · 2017 to 2026
$16.7M
Adult Brain Tumor Consortium (ABTC)UM1CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A · 2014 to 2020
$9.7M
Cancer Immunologic Data Commons (CIDC) Supplement RequestU24CA224316 · NCI · DANA-FARBER CANCER INST · PI CERAMI, ETHAN, MICHOR, FRANZISKA · 2017 to 2022
$6.8M
NCI NIH HHS U24 CA224285NCI NIH HHS U24 CA224309NCI NIH HHS U24 CA224316NCI NIH HHS UM1 CA137443
6 · The paper itself

Abstract

backgroundFor newly diagnosed glioblastoma (GBM), a combination of upfront surgical immunotherapy with aglatimagene besadenovec (CAN-2409), followed by chemoradiation and then adjuvant nivolumab has not been tested. The aim of this study was to test the safety of this regimen and determine metrics of immune activation that may correlate with clinical outcomes.

methodsForty-one patients with suspected newly diagnosed GBM by imaging were enrolled in this multi-institutional, open-label, phase 1b clinical trial before surgical resection. Frozen section confirmation of high-grade glioma was required for administration of CAN-2409. This was then followed with chemoradiation and adjuvant nivolumab. Tumor and blood were assayed for genetic and immune markers before and during treatment.

resultsThe regimen was well tolerated and generated measurable immune activation. Factors linked to survival were identified, such as baseline mutated gene pairs (eg, MED15/HRC), tumor immune cell composition, and changes in systemic cytokine, immune cells, and T-cell diversity. The most significant serial systemic immune changes were observed in a long-term survivor subset of patients with gross total resection (GTR)/methylated methylguanine methyltransferase (MGMT) promoter tumors. Median overall survival (mOS) in these patients was 30.6 months, while it was less for patients with unmethylated or subtotal resections.

conclusionsThese findings suggest the opportunity for patient stratification and the potential for more durable antitumor immune responses in future clinical trials of this multimodal standard of care and combined immunotherapy regimen. ClinicalTrials.gov identifier: NCT03576612.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsGlioblastomaImmunotherapyAdultAgedChemoradiotherapyCombined Modality TherapyFemaleFollow-Up StudiesHumansMaleMiddle AgedNivolumabPrognosisStandard of CareNivolumabbrain tumorclinical trialgene therapygliomaimmunotherapy

Identifiers

PMID40120123
PMCPMC12833529

What Socratic holds

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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 Socratic graph.