Evidence map›Paper›PMID 39831818›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025

First-in-Human Clinical Trial of a Small-Molecule EBNA1 Inhibitor, VK-2019, in Patients with Epstein-Barr-Positive Nasopharyngeal Cancer, with Pharmacokinetic and Pharmacodynamic Studies.

A Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun Lee, Maura L Gillison, Saad A Khan, Rong Lu, Benjamin A Pinsky, Samantha S Soldan and 3 more

Abstract readClinical Trial, Phase I
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
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

13 authors.

A Dimitrios ColevasDivision of Medical Oncology, Stanford University, Stanford, California.ORCID 0000-0003-3849-4264
Zahra TalebiThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.ORCID 0000-0001-9166-5160
Elizabeth WintersStanford University Medical Center, Stanford, California.ORCID 0009-0007-1872-8744
Caroline EvenGustave Roussy Cancer Centre, Villejuif, France.ORCID 0000-0002-8493-7444
Victor Ho-Fun LeeThe University of Hong Kong, Hong Kong, China.ORCID 0000-0002-6283-978X
Maura L GillisonUniversity of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-8145-5749
Saad A KhanDivision of Medical Oncology, Stanford University, Stanford, California.ORCID 0000-0002-3440-9774
Rong LuQuantitative Sciences Unit, Stanford University Medical Center, Stanford, California.ORCID 0000-0003-4321-9144
Benjamin A PinskyDepartment of Pathology, Stanford University, Stanford, California.ORCID 0000-0001-8751-4810
Samantha S SoldanThe Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0001-6263-519X
Olga VladmirovaThe Wistar Institute, Philadelphia, Pennsylvania.ORCID 0009-0004-1712-236X
Paul M LiebermanThe Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0002-3935-9921
Troy E MessickThe Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0001-7914-1524

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI MICHELLE A RUDEK · 1985 to 2026
$208.6M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Nan Zhang · 1985 to 2026
$75.9M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI John S. Witte · 2007 to 2026
$71.4M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
Targeting the Epigenetic and Metabolic Control of EBV-Epithelial CancersP01CA269043 · NCI · WISTAR INSTITUTE · PI PAUL M. LIEBERMAN · 2023 to 2026
$12.0M
Drugging EBNA1 to Treat EBV-Associated Cancers - Diversity SupplementR01CA259171 · NCI · WISTAR INSTITUTE · PI MESSICK, TROY E · 2021 to 2025
$3.3M
Phase one clinical trial of a novel small molecule EBNA1 inhibitor, VK-2019, in patients with Epstein- Barr positive nasopharyngeal cancer, with pharmacokinetic and pharmacodynamic correlative studiesR01CA235633 · NCI · STANFORD UNIVERSITY · PI COLEVAS, A. DIMITRIOS · 2019 to 2023
$3.0M
EBNA1 Inhibitor for Treatment of EBV-positive DLBCLR01CA282411 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M., MESSICK, TROY E · 2023 to 2025
$1.8M
Acquisition of a triple quadrupole mass spectrometer for small molecule analysisS10OD020091 · OD · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2015 to 2015
$314k
National Cancer Institute (NCI) P30CA006973National Cancer Institute (NCI) P30CA124435National Center for Advancing Translational Sciences (NCATS) UL1TR003098NCATS NIH HHS UL1 TR003098NCI NIH HHS P01 CA269043NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA124435NCI NIH HHS R01 CA235633NCI NIH HHS R01 CA259171NCI NIH HHS R01 CA282411NIH HHS S10 OD020091NIH Office of the Director (OD) S10OD020091
6 · The paper itself

Abstract

purposeA first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1). PATIENTS AND

methodsPharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

resultsVK-2019 was well tolerated. One patient achieved a partial response. Pharmacokinetic results demonstrated good systemic exposure, with high intersubject variability. Decreases in EBV DNA plasma levels were observed in some patients. VK-2019 reduced EBV genome copy number and viral gene expression in patient tumor samples and induced changes in immune cell markers.

conclusionsVK-2019 at dosages up to 1,800 mg daily demonstrated an acceptable safety profile, achieved micromolar plasma concentrations, and showed on-target biological activity in tumors from patients with advanced EBV-positive nasopharyngeal carcinoma.

Indexed as

Epstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensHerpesvirus 4, HumanNasopharyngeal CarcinomaNasopharyngeal NeoplasmsAdultAgedDNA, ViralFemaleHumansMaleMiddle AgedDNA, ViralEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear Antigens

Identifiers

PMID39831818
PMCPMC11915201

What Socratic holds

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Registered trials

None linked

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.