Delving into the Latest Updates on VK-2019 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

EBNA1

Action

inhibitors

Mechanism

EBNA1 inhibitors(Epstein-Barr nuclear antigen 1 inhibitors)

Therapeutic Areas

NeoplasmsMouth and Tooth DiseasesOtorhinolaryngologic Diseases+ [3]

Active Indication

Nasopharyngeal NeoplasmsDiffuse large B-cell lymphoma recurrentDiffuse large B-cell lymphoma refractory+ [1]

Inactive Indication

Epstein-Barr virus associated Nasopharyngeal CarcinomaNasopharyngeal Carcinoma

Originator Organization

Cullinan Oncology LLC

Active Organization

The Wistar Institute

Inactive Organization

Aienkang Clinical Medical Research (Beijing) Co., Ltd.

Cullinan Oncology LLC

Cullinan Pearl Corp.Startup

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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I期-主要目的：确定复发或转移性NPC患者中VK-2019单药治疗（口服）的MTD和RP2D。评价和表征复发或转移性NPC成人患者中VK-2019单用的安全性特征。I期-次要目的：根据RECIST v1.1评价VK-2019单药的抗肿瘤活性。表征复发或转移性NPC成人患者中单药VK-2019的单次给药和稳态药代动力学特征。在复发或转移性NPC成人患者中，通过减少VK-2019单药的血浆EBV-DNA，评价抗EBV活性。2a期-主要目的：评价复发或转移性NPC成人患者中VK-2019单药治疗（口服）的初步疗效（ORR、DOR、DCR、PFS、生存率和OS）。确认复发或转移性NPC成人患者中VK-2019单药治疗(口服)的安全性和耐受性。2a期-次要目的：进一步表征复发或转移性NPC成人患者中与VK-2019单药治疗（口服）相关的选定PK参数。在复发或转移性NPC成人患者中，通过减少VK-2019单药治疗(口服)的血浆EBV-DNA，评价抗EBV活性。（因字数限制，本试验的探索性目的请见相关说明栏）

[Translation]

Phase I - Primary Objective: Determine the MTD and RP2D of VK-2019 monotherapy (oral) in patients with recurrent or metastatic NPC. Evaluate and characterize the safety profile of VK-2019 monotherapy in adult patients with recurrent or metastatic NPC. Phase I - Secondary Objectives: Evaluate the anti-tumor activity of VK-2019 monotherapy according to RECIST v1.1. Characterize the single-dose and steady-state pharmacokinetic profile of VK-2019 monotherapy in adult patients with recurrent or metastatic NPC. Evaluate anti-EBV activity by reducing plasma EBV-DNA of VK-2019 monotherapy in adult patients with recurrent or metastatic NPC. Phase 2a - Primary Objective: Evaluate the preliminary efficacy (ORR, DOR, DCR, PFS, survival, and OS) of VK-2019 monotherapy (oral) in adult patients with recurrent or metastatic NPC. Confirm the safety and tolerability of VK-2019 monotherapy (oral) in adult patients with recurrent or metastatic NPC. Phase 2a - Secondary Objective: Further characterize selected PK parameters associated with VK-2019 monotherapy (oral) in adult patients with recurrent or metastatic NPC. Evaluate anti-EBV activity by reducing plasma EBV-DNA with VK-2019 monotherapy (oral) in adult patients with recurrent or metastatic NPC. (Due to word count limitations, please see the relevant description column for the exploratory purpose of this trial)

Start Date27 Dec 2019

Sponsor / Collaborator

Aienkang Clinical Medical Research (Beijing) Co., Ltd.

100 Clinical Results associated with VK-2019

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100 Translational Medicine associated with VK-2019

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100 Patents (Medical) associated with VK-2019

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2

Literatures (Medical) associated with VK-2019

03 Mar 2025·Clinical Cancer Research

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

Article

Author: Colevas, A. Dimitrios ; Lieberman, Paul M. ; Winters, Elizabeth ; Even, Caroline ; Soldan, Samantha S. ; Lu, Rong ; Khan, Saad A. ; Messick, Troy E. ; Talebi, Zahra ; Lee, Victor Ho-Fun ; Gillison, Maura L. ; Vladmirova, Olga ; Pinsky, Benjamin A.

AbstractPurpose: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.

01 Feb 2024·Biomedical Chromatography

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of VK‐2019, a selective EBNA1 inhibitor

Article

Author: Davis, Michael T. ; Colevas, A. Dimitrios ; Rudek, Michelle A. ; Messick, Troy E. ; Anders, Nicole M.

AbstractEBNA1 is an Epstein Barr virus (EBV) protein expressed in all EBV‐associated cancers. EBNA1 plays a critical role in the replication and maintenance of EBV episomes in latently infected cells. VK‐2019 was developed as a highly specific inhibitor of EBNA1 DNA binding activity and is currently in phase 1 development as a treatment for EBV‐associated carcinomas. A sensitive and reliable method was developed to quantify VK‐2019 in human plasma using liquid chromatography with tandem mass spectrometry to perform detailed pharmacokinetic studies. VK‐2019 was extracted from plasma using protein precipitation with acetonitrile. Separation of VK‐2019, two purported metabolites, and the internal standard, VK‐2019–d6, was achieved with a Zorbax XDB C18 column using a gradient flow over 6 min. VK‐2019 was detected using a SCIEX 4500 triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The assay range was 0.5–500 ng/mL and proved to be accurate and precise. Dilutions of 1:10 were accurately quantified. VK‐2019 was stable in plasma at −70°C for approximately 18 months. The method was applied to assess the total plasma concentrations of VK‐2019 in a patient who received a single and multiple oral daily doses of 120 mg.

100 Deals associated with VK-2019

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nasopharyngeal Neoplasms	Phase 2	-	The Wistar Institute	-
Nasopharyngeal Carcinoma	Preclinical	United States	Cullinan Pearl Corp.Startup	11 Mar 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	United States	-	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	France	-	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	Hong Kong	Cullinan Oncology LLC	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	United States	Cullinan Oncology LLC	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	China	Cullinan Oncology LLC	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	Singapore	Cullinan Oncology LLC	04 Apr 2019
Epstein-Barr virus associated Nasopharyngeal Carcinoma	Discovery	France	Cullinan Oncology LLC	04 Apr 2019
Nasopharyngeal Carcinoma	Discovery	United States	Cullinan Pearl Corp.Startup	11 Mar 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04925544 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Epstein-Barr virus associated Nasopharyngeal Carcinoma	22	VK-2019	(fimrjtsolr) = lrvekdtljs wiivvzvlsz (cbierknwjr ) View more	Positive	31 May 2023