Clinical Trial of a Novel Small Molecule EBNA1 Inhibitor, VK 2019, in Patients With Epstein Barr Virus (EBV)-Positive Nasopharyngeal Cancer (NPC) and Other Epstein-Barr Virus (EBV)-Associated Cancers, With Pharmacokinetic and Pharmacodynamic Correlative Studies

Inclusion Criteria:

• 1 Informed consent obtained prior to any protocol mandated study specific proceduresin accordance with institutional policies.

• 2 Either loco regionally recurrent or metastatic EBV positive RECIST evaluablenasopharyngeal carcinoma not amenable to curative treatment with no acceptedeffective standard of care therapeutic option.

Addendum for phase 2 exploratory cohorts: subjects with PTLD or EBV lymphoma not amenable to curative treatment with no accepted effective standard of care therapeutic option.

• 3 Not eligible for other approved or standard therapies

• 4.Prior palliative radiation must have been completed at least 2 weeks prior tostudy Cycle 1 Day 0

• 5.Prior anti cancer systemic treatment must have been completed greater than 4 weeksprior to the first dose of VK 2019 or subjects must have recovered from all acuteprior treatment related AEs

• 6.Toxicities related to prior anti cancer therapy must have returned to Grade 1 orless. Peripheral neuropathy must be Grade 2 or less. Chronic but stable toxicitiesGrade > 1 (eg, dysphasia, G tube dependence, etc.) are permissible.

• 7.Age ≥ 18

• 8.Absolute neutrophil count > 1500/µL (stable off any growth factor for at least 1week of study drug administration)

• 9.Hemoglobin > 9g/dL (transfusion to achieve this level is permitted)

• 10.Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOTpermitted)

• 11.Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 xupper limit of normal (ULN) .Total serum bilirubin ≤ 1.5 x ULN

• 12.Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min as calculatedper Cockcroft Gault equation

• 13.Urinary protein < 2+ by dipstick. If dipstick ≥ 2+, then a 24 hour urinecollection can be done and the subject may enter only if urinary protein is < 1 g/24hour

• 14.Sexually active subjects must agree to utilize birth control method duringtreatment and for 18 weeks after the last dose of VK 2019.

• 15.Eastern Cooperative Oncology Group (ECOG) performance status 2 or less.

• 16.Ability to understand and the willingness to personally sign the written IRBapproved informed consent document.

Exclusion Criteria:

• 1.Prior therapy restrictions.

• 2.Concurrent treatment with systemic cancer directed therapy includingcomplementary, alternative, herbal or nutritional supplement based treatments whosepurpose is for anti cancer effect

• 3.Severe or active symptomatic cardiopulmonary diseases, including unstable angina,congestive heart failure, or peripheral vascular disease within 12 months prior tostudy drug administration; and/or chronic obstructive pulmonary disease exacerbationor other respiratory illness requiring hospitalization within 4 weeks prior to studydrug administration. Subjects with effectively treated conditions (eg, stenting forcoronary artery disease) are eligible if stable for at least 4 weeks prior to studydrug administration

• 4.Metastatic disease with active central nervous system (CNS) involvement, definedas parenchymal brain involvement. Subjects with cranial nerve or base of skullinvolvement without the above are eligible. Subjects with CNS metastases that arestable on imaging at least 1 month following focal treatment with radiation areeligible

• 5.Known history of human immunodeficiency virus (HIV) unless the HIV positivesubjects has:

1. A stable regimen of highly active anti retroviral therapy (HAART)

2. No requirement for concurrent antibiotics or antifungal agents for theprevention of opportunistic infections

3. A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standardPCR based test

• 6.Serious uncontrolled medical disorder or active infection which would, in theopinion of the Investigator, impair the ability of the subject to receive protocoltherapy or whose control may be jeopardized by the complications of this therapy

• 7.NPC subjects: Have received a prior organ allograft or allogeneic bone marrowtransplant.

• 8.Current non prescription drug or alcohol dependence

• 9.For all female subjects: pregnancy or breastfeeding

• 10.All female subjects with reproductive potential must have a negative pregnancytest (serum or urine) prior to enrollment

• 11.Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation or studydrug administration, or may interfere with the interpretation of study results, orin the judgment of the investigator would make the subject inappropriate for entryinto the study

• 12.Corrected QT by Fridericia's formula (QTcF) of > 470 ms average (mean) ontriplicate ECG performed during screening