Clinical Trials /

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

NCT03682055

Description:

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.

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: VK-2019-001
  • NCT ID: NCT03682055

Conditions

  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Cancer

Interventions

DrugSynonymsArms
VK-2019Phase 1 Dose Escalation (Accelerated Titration)

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose Escalation (Accelerated Titration)ExperimentalVK-2019 QD in Accelerated Titration dose escalation cohorts enrolling EBV+ NPC
  • VK-2019
Phase 1 Dose Escalation (Rolling Six)ExperimentalVK-2019 QD in Rolling Six dose escalation cohorts enrolling EBV+ NPC.
  • VK-2019
Phase 1 Dose Expansion(s)ExperimentalVK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified criteria for clinical and/or biological activity.
  • VK-2019
Phase 2a Dose Expansion(s)ExperimentalVK-2019 QD in expansion cohorts that may be opened at doses that meet pre-specified efficacy criteria in Phase 1 Dose Escalation cohorts.
  • VK-2019

Eligibility Criteria

        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_5
             08.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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:All Cohorts: The frequency, severity, and duration of AEs and DLTs, AEs leading to discontinuation, and AEs leading to death.
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:All Cohorts: Incidence of safety laboratory assessment abnormalities
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Incidence of abnormalities in vital signs or other clinical safety assessments.
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR
Time Frame:24 months
Safety Issue:
Description:
Measure:Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Rate of partial or complete plasma EBV DNA antiviral response during treatment (assessed as 3xlog10 reduction or a drop below the lower limit of detection of the assay [LLOD], respectively).
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Maximum measured concentration in serum (Cmax)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Minimum measured concentration in serum (Cmin)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Time from dosing to maximum measured concentration (tmax)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Area under the serum concentration-time curve (AUC)
Time Frame:24 months
Safety Issue:
Description:
Measure:All Cohorts: Terminal half-life (t1/2)
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cullinan Apollo Corporation

Trial Keywords

  • Epstein-Barr Virus
  • Nasopharyngeal Carcinoma
  • NPC
  • EBV
  • EBNA1 inhibitor
  • VK-2019
  • Nasopharynx cancer
  • Nasopharynx carcinoma

Last Updated

January 7, 2020