Faculty, Staff and Student Publications

Language

English

Publication Date

3-3-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-24-2814

PMID

39831818

PMCID

PMC11915201

PubMedCentral® Posted Date

9-3-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Humans, Herpesvirus 4, Human, Male, Female, Middle Aged, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Nasopharyngeal Neoplasms, Adult, Aged, Nasopharyngeal Carcinoma, DNA, Viral

Published Open-Access

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