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

Primary Purpose

Nasopharyngeal Carcinoma, Nasopharyngeal Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VK-2019
Sponsored by
Cullinan Oncology, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring Epstein-Barr Virus, Nasopharyngeal Carcinoma, NPC, EBV, EBNA1 inhibitor, VK-2019, Nasopharynx cancer, Nasopharynx carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University, School of Medicine, Stanford Cancer Institute
  • The University of Texas - MD Anderson Cancer Center
  • Sun Yat Sen University Cancer Center
  • Institut Gustave Roussy
  • Hong Kong University - Queen Mary Hospital
  • National Cancer Centre Singapore

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1 Dose Escalation (Accelerated Titration)

Phase 1 Dose Escalation (Rolling Six)

Phase 1 Dose Expansion(s)

Phase 2a Dose Expansion(s)

Arm Description

VK-2019 QD in Accelerated Titration dose escalation cohorts enrolling EBV+ NPC

VK-2019 QD in Rolling Six dose escalation cohorts enrolling EBV+ NPC.

VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified criteria for clinical and/or biological activity.

VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified efficacy criteria in Phase 1 Dose Escalation cohorts.

Outcomes

Primary Outcome Measures

All Cohorts: The Frequency, Severity, and Duration of AEs and DLTs, AEs Leading to Discontinuation, and AEs Leading to Death.

Secondary Outcome Measures

Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR

Full Information

First Posted
September 20, 2018
Last Updated
July 24, 2023
Sponsor
Cullinan Oncology, LLC
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03682055
Brief Title
Phase 1/2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
April 4, 2019 (Actual)
Primary Completion Date
June 23, 2020 (Actual)
Study Completion Date
August 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cullinan Oncology, LLC
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma, Nasopharyngeal Cancer
Keywords
Epstein-Barr Virus, Nasopharyngeal Carcinoma, NPC, EBV, EBNA1 inhibitor, VK-2019, Nasopharynx cancer, Nasopharynx carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Dose Escalation (Accelerated Titration)
Arm Type
Experimental
Arm Description
VK-2019 QD in Accelerated Titration dose escalation cohorts enrolling EBV+ NPC
Arm Title
Phase 1 Dose Escalation (Rolling Six)
Arm Type
Experimental
Arm Description
VK-2019 QD in Rolling Six dose escalation cohorts enrolling EBV+ NPC.
Arm Title
Phase 1 Dose Expansion(s)
Arm Type
Experimental
Arm Description
VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified criteria for clinical and/or biological activity.
Arm Title
Phase 2a Dose Expansion(s)
Arm Type
Experimental
Arm Description
VK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified efficacy criteria in Phase 1 Dose Escalation cohorts.
Intervention Type
Drug
Intervention Name(s)
VK-2019
Intervention Description
EBNA1 inhibitor
Primary Outcome Measure Information:
Title
All Cohorts: The Frequency, Severity, and Duration of AEs and DLTs, AEs Leading to Discontinuation, and AEs Leading to Death.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent obtained prior to any protocol mandated assessment. Age ≥ 18. 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. Prior palliative radiation must have been completed at least 2 weeks prior to study Cycle 1 Day 0. Prior anti cancer systemic treatment must have been completed greater than 4 weeks prior to study Cycle 1 Day 0. 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. 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. ECOG performance status score of ≤ 2 at study entry. Absolute neutrophil count > 1500/µL (stable off any growth factor within 1 week of study drug administration). Hemoglobin > 9g/dL (transfusion to achieve this level is permitted). Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOT permitted). Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN). Total serum bilirubin ≤ 1.5 x ULN. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculated per Cockcroft Gault equation. 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. 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. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures. Exclusion Criteria: 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. 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. Concurrent treatment with systemic cancer directed therapy including complementary, alternative, herbal or nutritional supplement based treatments whose purpose is for anti cancer effect. 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 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. Currently taking drugs that inhibit or induce OATP1B1 or OATP1B3 within 5 half lives of that agent. Examples are included in Appendix 2. Have received a prior organ allograft or allogeneic bone marrow transplant. Current non prescription drug or alcohol dependence. For all female patients, pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. 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. Corrected QT by Fridericia's formula (QTcF) of > 470 ms.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A. Dimitrios Colevas, MD
Organizational Affiliation
Stanford Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford University, School of Medicine, Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
The University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Sun Yat Sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Hong Kong University - Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
National Cancer Centre Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25367333
Citation
Young LS. Epstein-Barr virus at 50-future perspectives. Chin J Cancer. 2014 Nov;33(11):527-8. doi: 10.5732/cjc.014.10208.
Results Reference
background
PubMed Identifier
25418193
Citation
Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer. 2014 Dec;33(12):581-90. doi: 10.5732/cjc.014.10197. Epub 2014 Nov 21.
Results Reference
background
PubMed Identifier
28893937
Citation
Tsao SW, Tsang CM, Lo KW. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19;372(1732):20160270. doi: 10.1098/rstb.2016.0270.
Results Reference
background

Learn more about this trial

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

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