Phase 1/2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)

July 24, 2023 updated by: Cullinan Oncology, LLC

Phase 1/2a Open Label, Multicenter Clinical Trial of a Novel Small Molecule EBNA1 Inhibitor, VK 2019, in Patients With Epstein Barr Virus Positive Nasopharyngeal Cancer, With Pharmacokinetic and Pharmacodynamic Correlative Studies

VK-2019-001 is a 1/2a trial of the oral EBNA-1 targeting agent VK-2019 in patients with EBV-positive recurrent or metastatic NPC to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D), as well as to evaluate the PK profile of VK-2019.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/2a, open-label, multicenter, first-in-human trial to evaluate the safety and tolerability, PK, PD, and preliminary efficacy of VK-2019 in patients with EBV-positive NPC.

This trial is divided into three parts: Phase 1 Dose Escalation, Phase 1 Dose Expansion, and Phase 2s Dose Expansion.

The objectives of the dose escalation part are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), and to evaluate the anti-tumor activity of orally administered VK-2019 monotherapy. Additional objectives are to determine the pharmacokinetic (PK) profile of VK-2019.

VK-2019 will be dosed once daily (QD).

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat Sen University Cancer Center
  • France
      • Villejuif, France, 94800
        • Institut Gustave Roussy
  • Hong Kong
      • Hong Kong, Hong Kong
        • Hong Kong University - Queen Mary Hospital
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Centre Singapore
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University, School of Medicine, Stanford Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas - MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Informed consent obtained prior to any protocol mandated assessment.
  2. Age ≥ 18.
  3. Either loco regionally recurrent or metastatic EBV positive nasopharyngeal carcinoma not amenable to curative treatment. EBV positivity is defined as high EBV viral load in plasma (> 4000 genomes per µg plasma DNA) and/or biopsy tissue positive for EBV.
  4. Prior palliative radiation must have been completed at least 2 weeks prior to study Cycle 1 Day 0.
  5. Prior anti cancer systemic treatment must have been completed greater than 4 weeks prior to study Cycle 1 Day 0.
  6. Toxicities related to prior anti-cancer therapy must have returned to Grade 1 or less. Peripheral neuropathy must be Grade 2 or less. Chronic but stable toxicities Grade > 1 (e.g., dysphasia, G tube dependence, etc.) may be allowed after agreement between the Investigator and Sponsor.
  7. For the dose expansion phase only: Patients must have RECIST v1.1 measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non nodal lesions and short axis for nodal lesions) as ≥ 10 mM with spiral CT scan, MRI, or calipers by clinical exam.
  8. ECOG performance status score of ≤ 2 at study entry.
  9. Absolute neutrophil count > 1500/µL (stable off any growth factor within 1 week of study drug administration).
  10. Hemoglobin > 9g/dL (transfusion to achieve this level is permitted).
  11. Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOT permitted).
  12. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN).
  13. Total serum bilirubin ≤ 1.5 x ULN.
  14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculated per Cockcroft Gault equation.
  15. Urinary protein < 2+ by dipstick. If dipstick ≥ 2+, then a 24 hour urine collection can be done and the patient may enter only if urinary protein is < 1 g/24 hour.
  16. Sexually active patients must agree to utilize birth control method during the study and for 18 weeks after the study is concluded, using effective birth control methods as defined in https://www.cdc.gov/reproductivehealth/unintendedpregnancy/pdf/contraceptive_methods_508.pdf.
  17. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion Criteria:

  1. Severe or active symptomatic cardiopulmonary diseases (unstable angina and/or congestive heart failure or peripheral vascular disease within the last 12 months; chronic obstructive pulmonary disease exacerbation other respiratory illness requiring hospitalization) or clinically significant psychiatric disorders; patients with effectively treated conditions (eg, stenting for CAD) are eligible.
  2. Metastatic disease with active central nervous system (CNS) involvement, defined as parenchymal brain involvement. Patients with cranial nerve or base of skull involvement without the above are eligible; Patients with CNS metastases stable 1 month following focal treatment with radiation are eligible.
  3. Concurrent treatment with systemic cancer directed therapy including complementary, alternative, herbal or nutritional supplement based treatments whose purpose is for anti cancer effect.

  4. Positive for human immunodeficiency virus (HIV) are not excluded from this study, but HIV positive patients must have:

    • A stable regimen of highly active anti retroviral therapy (HAART)
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
    • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR based test
  5. Serious uncontrolled medical disorder or active infection which would, in the opinion of the Investigator, impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
  6. Currently taking drugs that inhibit or induce OATP1B1 or OATP1B3 within 5 half lives of that agent. Examples are included in Appendix 2.
  7. Have received a prior organ allograft or allogeneic bone marrow transplant.
  8. Current non prescription drug or alcohol dependence.
  9. For all female patients, pregnancy or breastfeeding.
  10. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment.
  11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
  12. Corrected QT by Fridericia's formula (QTcF) of > 470 ms.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Dose Escalation (Accelerated Titration)
VK-2019 QD in Accelerated Titration dose escalation cohorts enrolling EBV+ NPC
Drug: VK-2019
EBNA1 inhibitor
Experimental: Phase 1 Dose Escalation (Rolling Six)
VK-2019 QD in Rolling Six dose escalation cohorts enrolling EBV+ NPC.
Drug: VK-2019
EBNA1 inhibitor
Experimental: Phase 1 Dose Expansion(s)
VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified criteria for clinical and/or biological activity.
Drug: VK-2019
EBNA1 inhibitor
Experimental: Phase 2a Dose Expansion(s)
VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified efficacy criteria in Phase 1 Dose Escalation cohorts.
Drug: VK-2019
EBNA1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All Cohorts: The Frequency, Severity, and Duration of AEs and DLTs, AEs Leading to Discontinuation, and AEs Leading to Death.
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR
Time Frame: 24 months
24 months

Other Outcome Measures

Outcome Measure
Time Frame
Phase 2a Dose Expansion Cohorts: Exploratory PD assay for EBER in situ hybridization levels in baseline and on treatment tumor biopsies in a limited number of patients at MTD.
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cullinan Oncology, LLC

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: A. Dimitrios Colevas, MD, Stanford Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 4, 2019

Primary Completion (Actual)

June 23, 2020

Study Completion (Actual)

August 8, 2020

Study Registration Dates

First Submitted

September 20, 2018

First Submitted That Met QC Criteria

September 21, 2018

First Posted (Actual)

September 24, 2018

Study Record Updates

Last Update Posted (Actual)

August 15, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VK-2019-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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