Phase 1/2a Study of VK-2019 in Patients With Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma (NPC)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03682055 |
Recruitment Status :
Terminated
(Lack of efficacy)
First Posted : September 24, 2018
Last Update Posted : October 19, 2020
|
- Study Details
- Tabular View
- Results Submitted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Nasopharyngeal Carcinoma Nasopharyngeal Cancer | Drug: VK-2019 | Phase 1 Phase 2 |
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 (Clinical Trial) |
Actual Enrollment : | 14 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | April 4, 2019 |
Actual Primary Completion Date : | June 23, 2020 |
Actual Study Completion Date : | August 8, 2020 |

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 |
- All Cohorts: The frequency, severity, and duration of AEs and DLTs, AEs leading to discontinuation, and AEs leading to death. [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: The durable overall response rate (ORR). [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: ORR [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: Duration of response (DOR) [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: Six month disease control rate (DCR-6) [ Time Frame: 30 months ]
- Phase 2a Dose Expansion Cohorts: Twelve month disease control rate (DCR-12) [ Time Frame: 36 months ]
- Phase 2a Dose Expansion Cohorts: Progression Free Survival (PFS) [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: Rate of survival [ Time Frame: 24 months ]
- Phase 2a Dose Expansion Cohorts: Overall survival (OS) [ Time Frame: 24 months ]
- All Cohorts: Incidence of safety laboratory assessment abnormalities [ Time Frame: 24 months ]
- All Cohorts: Incidence of abnormalities in vital signs or other clinical safety assessments. [ Time Frame: 24 months ]
- Phase 1 Dose Escalation and Dose Expansion Cohorts: ORR [ Time Frame: 24 months ]
- Phase 1 Dose Escalation and Dose Expansion Cohorts: DOR [ Time Frame: 24 months ]
- Phase 1 Dose Escalation and Dose Expansion Cohorts: DCR [ Time Frame: 24 months ]
- 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 ]
- All Cohorts: Maximum measured concentration in serum (Cmax) [ Time Frame: 24 months ]
- All Cohorts: Minimum measured concentration in serum (Cmin) [ Time Frame: 24 months ]
- All Cohorts: Time from dosing to maximum measured concentration (tmax) [ Time Frame: 24 months ]
- All Cohorts: Area under the serum concentration-time curve (AUC) [ Time Frame: 24 months ]
- All Cohorts: Terminal half-life (t1/2) [ Time Frame: 24 months ]
- 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 ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03682055
United States, California | |
Stanford University, School of Medicine, Stanford Cancer Institute | |
Stanford, California, United States, 94305 | |
United States, Texas | |
The University of Texas - MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
China, Guangdong | |
Sun Yat Sen University Cancer Center | |
Guangzhou, Guangdong, China, 510060 | |
France | |
Institut Gustave Roussy | |
Villejuif, France, 94800 | |
Hong Kong | |
Hong Kong University - Queen Mary Hospital | |
Hong Kong, Hong Kong | |
Singapore | |
National Cancer Centre Singapore | |
Singapore, Singapore, 169610 |
Study Chair: | A. Dimitrios Colevas, MD | Stanford Cancer Institute |
Responsible Party: | Cullinan Oncology, LLC |
ClinicalTrials.gov Identifier: | NCT03682055 |
Other Study ID Numbers: |
VK-2019-001 |
First Posted: | September 24, 2018 Key Record Dates |
Last Update Posted: | October 19, 2020 |
Last Verified: | October 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Epstein-Barr Virus Nasopharyngeal Carcinoma NPC EBV |
EBNA1 inhibitor VK-2019 Nasopharynx cancer Nasopharynx carcinoma |
Epstein-Barr Virus Infections Carcinoma Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Head and Neck Neoplasms |
Neoplasms by Site Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Herpesviridae Infections DNA Virus Infections Virus Diseases Infections Tumor Virus Infections |