Evidence map›Paper›PMID 37188783›Full record

Trial reportNature medicine2023

Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial.

Farshad Nassiri, Vikas Patil, Leeor S Yefet, Olivia Singh, Jeff Liu, Rachel M A Dang, Takafumi N Yamaguchi, Mariza Daras, Timothy F Cloughesy, Howard Colman and 29 more

Erratum issued 2 registry-linked trialsOpen access · hybridAbstract readMulticenter StudyClinical Trial, Phase IIClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 221 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
221citing papers in PubMed, 7 pooled it
76.4field-weighted citation impact, top 1% of its field
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.

NCT02798406 phase2completednot on this map

A Phase II, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) With Pembrolizumab (KEYTRUDA®) for Recurrent Glioblastoma or Gliosarcoma (CAPTIVE/KEYNOTE-192)

TypeinterventionalSponsorDNAtrix, Inc.Ran2016 to 2021Enrolled49ConditionsBrain Cancer, Brain Neoplasm, Glioma, GlioblastomaArmsDNX-2401, pembrolizumab
NCT07424092 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Intratumoral DNX-2401 Administration for Recurrent and Refractory High Grade Brain Tumors in Pediatric and Young Adult Patients

TypeinterventionalSponsorClinica Universidad de Navarra, Universidad de NavarraRan2026 to 2029Enrolled39ConditionsHigh Grade Glioma, Ependymoma, Embryonal Tumor of Brain, RecurrenceArmsDNX-2401
3 · Its place in the literature

Who cites it

221 citing papers in PubMed, 7 syntheses or guidelines pooled it, 245 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. The effect of oncolytic virotherapy on pediatric brain tumor- a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
    Pooled it
  5. Pooled it
  6. Anti-PD-1 and anti-PD-L1 antibodies for glioma.The Cochrane database of systematic reviews · 2025
    Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Systemic Immune Correlates of Long-term Survival after Delta-24-RGD Based on the Therapeutic Adenovirus for Recurrent Glioblastoma Effect Trial (TARGET).Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Review
  16. Article
  17. Next-generation therapeutics for glioblastoma: Challenges and future directions.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  18. Review
  19. Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  20. Review

161 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

39 authors at 20 institutions in 4 countries.

Farshad NassiriDivision of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-0797-3425
Vikas PatilPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Leeor S YefetPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Olivia SinghPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0001-7321-6775
Jeff LiuPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Rachel M A DangDepartment of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Takafumi N YamaguchiDepartment of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Mariza DarasDivision of Neuro-oncology, University of California San Francisco, San Francisco, CA, USA.
Timothy F CloughesyUCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-8656-7483
Howard ColmanHuntsman Cancer Institute and Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.
Priya U KumthekarDepartment of Neurology, Division of Neuro-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Clark C ChenDepartment of Neurosurgery, University of Minnesota, Minneapolis, MI, USA.ORCID 0000-0001-9544-2570
Robert AikenRutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
Morris D GrovesDepartment of Neurology, Texas Oncology, Austin, TX, USA.
Shirley S OngDivision of Neuro-Oncology, Department of Neurology, the Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Rohan RamakrishnaDepartment of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.
Michael A VogelbaumDepartment of Neuro-Oncology, Neuro-Oncology Program, Moffitt Cancer Center, Tampa, FL, USA.
Simon KhagiDivision of Medical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thomas KaleyDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jason M MelearDepartment of Internal Medicine, Baylor University Medical Center, Dallas, TX, USA.
David M PeereboomThe Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA.
Analiz RodriguezDepartment of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AK, USA.
Maxim YankelevichDepartment of Pediatrics, University of Michigan, Ann Arbor Beaumont Children's Hospital, Royal Oak, MI, USA.
Suresh G NairLehigh Valley Topper Cancer Institute, Allentown, PA, USA.
Vinay K PuduvalliDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kenneth AldapeLaboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0001-5119-7550
Andrew GaoDepartment of Laboratory Medicine and Pathobiology, University Health Network, Toronto, Ontario, Canada.
Álvaro López-JaneiroDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Carlos E de AndreaDepartment of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Marta M AlonsoNavarra Institute for Health Research (IdISNA), Pamplona, Spain.ORCID 0000-0002-7520-7351
Paul BoutrosDepartment of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-0553-7520
Joan RobbinsDNATrix Inc., Carlsbad, CA, USA.
Warren P MasonPrincess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Adam M SonabendDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Roger StuppDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID 0000-0002-5483-3118
Juan FueyoDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Candelaria Gomez-ManzanoDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-1259-2133
Frederick F LangDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0003-3747-873X
Gelareh ZadehDivision of Neurosurgery, University of Toronto, Toronto, Ontario, Canada. gelareh.zadeh@uhn.ca.ORCID 0000-0002-6637-4502
University Health Network · CAThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · USNavarre Institute of Health Research · ESNorthwestern University · USBaylor University Medical Center · USCleveland Clinic · USLehigh Valley Hospital-Pocono · USLineage Cell Therapeutics (United States) · USMemorial Sloan Kettering Cancer Center · USMoffitt Cancer Center · USNational Cancer Institute · USNewYork–Presbyterian Hospital · USRutgers, The State University of New Jersey · USTexas Oncology · USThe Ohio State University Wexner Medical Center · USUniversity of Arkansas for Medical Sciences · USUniversity of California, San Francisco · USUniversity of Michigan · USUniversity of Minnesota · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo, FREDERICK F LANG · 2008 to 2026
$41.2M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA127001NCI NIH HHS P50 CA211015
6 · The paper itself

Abstract

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).

Indexed as

GlioblastomaOncolytic VirotherapyOncolytic VirusesAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsHumansNeoplasm Recurrence, LocalAntibodies, Monoclonal, Humanizedpembrolizumab

Identifiers

PMID37188783
PMCPMC10287560
OpenAlexW4376609298

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.