2. Academic Validation
  3. 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

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

  • Clin Cancer Res. 2025 Mar 3;31(5):815-823. doi: 10.1158/1078-0432.CCR-24-2814.
A Dimitrios Colevas 1,  Zahra Talebi 2,  Elizabeth Winters 3,  Caroline Even 4,  Victor Ho-Fun Lee 5,  Maura L Gillison 6,  Saad A Khan 1,  Rong Lu 7,  Benjamin A Pinsky 8,  Samantha S Soldan 9,  Olga Vladmirova 9,  Paul M Lieberman 9,  Troy E Messick 9
Affiliations

Affiliations

  • 1 Division of Medical Oncology, Stanford University, Stanford, California.
  • 2 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
  • 3 Stanford University Medical Center, Stanford, California.
  • 4 Gustave Roussy Cancer Centre, Villejuif, France.
  • 5 The University of Hong Kong, Hong Kong, China.
  • 6 University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 7 Quantitative Sciences Unit, Stanford University Medical Center, Stanford, California.
  • 8 Department of Pathology, Stanford University, Stanford, California.
  • 9 The Wistar Institute, Philadelphia, Pennsylvania.
PMID: 39831818 DOI: 10.1158/1078-0432.CCR-24-2814
Abstract

Purpose: A 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 methods: Pharmacokinetic 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.

Results: VK-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.

Conclusions: VK-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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-W725179
    99.97%, EBNA1 Inhibitor
    EBV