VK-2019 for Nasopharyngeal Cancer

Overseen By Elizabeth Winters

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Anticancer therapies

Disqualifiers: Cardiopulmonary diseases, CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, VK-2019 (an Epstein-Barr Nuclear Antigen 1 inhibitor), for nasopharyngeal cancer linked to the Epstein-Barr virus (EBV), particularly for those lacking other standard treatment options. Researchers aim to assess VK-2019's effectiveness against this cancer type. Suitable candidates for this trial include individuals with EBV-related nasopharyngeal cancer that has recurred or metastasized and cannot be cured with existing treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you do not take any other systemic cancer treatments, including complementary or alternative therapies, while participating. It does not specify about other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that VK-2019 is likely to be safe for humans?

Research has shown that VK-2019 is safe for treating nasopharyngeal cancer. In earlier studies, patients tolerated VK-2019 well, even at doses as high as 1,800 mg per day, indicating that most did not experience serious side effects. The drug reached the necessary levels in the body to potentially act against the targeted cancer. One study found fewer side effects because the drug specifically targets a part of the cancer cells absent in normal cells. This specificity helps protect healthy cells, which is promising for safety. Overall, current studies suggest that VK-2019 is safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for nasopharyngeal cancer?

VK-2019 is unique because it offers a new approach for treating nasopharyngeal cancer. Unlike the standard treatments, which often involve chemotherapy and radiation, VK-2019 is an experimental drug that targets cancer cells differently. It uses a novel mechanism of action with dose escalation and expansion, aiming to maximize its effectiveness at 1800 mg twice daily. Researchers are excited about VK-2019 because it could provide a more targeted therapy with potentially fewer side effects, offering hope for better management of this cancer type.

What evidence suggests that VK-2019 might be an effective treatment for nasopharyngeal cancer?

Research has shown that VK-2019, which participants in this trial will receive, is being tested as a potential treatment for nasopharyngeal cancer linked to the Epstein-Barr virus (EBV). Early results indicate that VK-2019 is generally safe for patients and achieves levels in the body higher than those effective in lab studies. In one study, a patient’s tumor shrank, suggesting the treatment can reduce tumors in some cases. These findings offer hope for individuals without other standard treatment options for this type of cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

A. Dimitrios Colevas

Principal Investigator

Stanford Universiy

Are You a Good Fit for This Trial?

Adults with EBV-positive nasopharyngeal cancer not eligible for standard treatments can join. They must have good kidney function, controlled protein in urine, agree to birth control use, and be generally well enough (ECOG ≤2). Prior treatments should be completed with recovered side effects (except stable chronic issues), and blood counts need to meet specific levels.

Inclusion Criteria

Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOT permitted)

My white blood cell count is healthy without medication.

My urine protein levels are low, under 1g/24 hours if tested with a 24-hour collection.

Exclusion Criteria

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 subject inappropriate for entry into the study

I am not pregnant, confirmed by a test.

I am HIV positive but have a stable condition with effective treatment, no opportunistic infections, a CD4 count above 250, and an undetectable viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VK 2019 in cycles of 28 days, up to 12 cycles, until progression or dose limiting toxicity

12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Extension

Participants may continue to be monitored for overall survival and progression-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• VK-2019

Trial Overview The trial is testing VK-2019's effectiveness against EBV-related nasopharyngeal carcinoma when no other treatment options are available. It includes pharmacokinetic and pharmacodynamic studies to understand how the drug behaves in the body and its biological effects.

How Is the Trial Designed?

Group I: VK-2019_arm Experimental Treatment 1 Intervention

Dose escalation and expansion up to 31 additional patients at a maximum of 1800 mg twice daily. Cycles will be defined as 28 days of treatment, subjects will receive VK 2019 until progression or dose limiting toxicity, for up to 12 cycles.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Silencing the Epstein-Barr virus nuclear antigen 1 (EBNA1) in nasopharyngeal carcinoma (NPC) cells significantly inhibited their growth and induced a G1-phase cell cycle arrest, suggesting a potential therapeutic target for NPC.

The study demonstrated that down-regulation of EBNA1 led to decreased levels of key cell cycle regulators (c-myc, CDK4, CDK6, and pRb), which are crucial for cell proliferation, indicating a mechanism by which EBNA1 promotes cancer cell growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Epstein-Barr virus nuclear antigen 1 on cell proliferation and cell cycle in nasopharyngeal carcinoma cells]. Wan, RQ., Li, XP., Wang, L., et al.[2019]

The study identified a new subvariant of the EBV EBNA1 gene, specifically P-Thr-sv-5, which shows significant clustering in nasopharyngeal carcinoma (NPC) cases, suggesting its potential as a viral biomarker for this type of cancer.

Statistical analysis of 40 NPC biopsies, 31 mononucleosis plasma samples, and 16 renal transplant plasma samples revealed distinct differences in EBNA1 subvariant distribution, indicating that certain EBNA1 polymorphisms may be associated with the development of malignancies like NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sequence analysis of Epstein-Barr virus EBNA1 gene: could viral screening markers for nasopharyngeal carcinoma be identified? Banko, AV., Lazarevic, IB., Karalic, DZ., et al.[2020]

The small molecule inhibitor VK-1727 effectively inhibits cell growth and proliferation in EBV-positive gastric carcinoma (EBVaGC) models, demonstrating selective action against these cancer cells.

In animal studies, VK-1727 significantly reduced tumor growth in EBVaGC xenografts, suggesting that targeting the Epstein-Barr virus nuclear antigen 1 (EBNA1) could be a promising treatment strategy for patients with this type of gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBNA1 inhibitors have potent and selective antitumor activity in xenograft models of Epstein-Barr virus-associated gastric cancer. Soldan, SS., Anderson, EM., Frase, DM., et al.[2022]

The meta-analysis of 21 studies involving 2986 nasopharyngeal carcinoma (NPC) patients and 3507 controls found that serum VCA-IgA has a high diagnostic accuracy for NPC, with a sensitivity of 83% and specificity of 88%.

Combining multiple EBV antigens for testing significantly improved diagnostic performance, achieving a sensitivity of 93% and specificity of 95%, suggesting that using a panel of tests may be more effective than relying solely on the VCA-IgA assay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Value of Serum Epstein-Barr Virus Capsid Antigen-IgA for Nasopharyngeal Carcinoma: a Meta-Analysis Based on 21 Studies. Chen, Y., Xin, X., Cui, Z., et al.[2019]

VK-2019 is a specific inhibitor of the EBNA1 protein from the Epstein Barr virus, which is crucial for the replication of EBV in cancer cells, and is currently being tested in phase 1 trials for treating EBV-associated cancers.

A reliable method for measuring VK-2019 levels in human plasma was developed, showing that the drug is stable for up to 18 months at -70°C, which is important for understanding its pharmacokinetics in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of VK-2019, a selective EBNA1 inhibitor. Davis, MT., Anders, NM., Colevas, AD., et al.[2023]

The study found that the EBV-encoded protein EBNA 1, when expressed in an EBV-negative nasopharyngeal carcinoma (NPC) cell line, led to less differentiated cell growth and increased tumorigenicity and metastasis in mice.

These findings suggest that EBNA 1 may significantly contribute to the aggressive progression of NPC, highlighting its potential role in the disease's development and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced malignant progression of nasopharyngeal carcinoma cells mediated by the expression of Epstein-Barr nuclear antigen 1 in vivo. Sheu, LF., Chen, A., Meng, CL., et al.[2006]

The study identified the V-val subtype of the Epstein-Barr virus nuclear antigen (EBNA)-1 as the dominant variant in Chinese populations, particularly in cases of nasopharyngeal carcinoma (NPC) and Hodgkin's disease, suggesting its significant role in these malignancies.

In contrast, the V-val subtype was not found in Danish samples, indicating that it is not restricted to the oral compartment and may be more prevalent in Asian populations, highlighting geographical differences in EBV-associated tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction. Sandvej, K., Zhou, XG., Hamilton-Dutoit, S.[2022]

EBNA1 protein is highly expressed in nasopharyngeal carcinoma (NPC) tissues and is linked to lymph node metastasis, suggesting its potential role as a biomarker for cancer progression.

Overexpression of EBNA1 in NPC cell lines promotes epithelial-mesenchymal transition (EMT) by inhibiting microRNA 200a and 200b, leading to increased levels of ZEB1 and ZEB2, which are key regulators of EMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells. Wang, L., Tian, WD., Xu, X., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39831818/

First-in-Human Clinical Trial of a Small-Molecule EBNA1 ... Conclusions: VK-2019 at dosages up to 1,800 mg daily demonstrated an acceptable safety profile, achieved micromolar plasma concentrations, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11915201/

First-in-Human clinical trial of a small molecule EBNA1 ... VK-2019 at doses up to 1800 mg daily demonstrated an acceptable safety profile, achieved micromolar plasma concentrations, and showed on-target biological ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6035

Phase I/IIa clinical trial of a small molecule EBNA1 inhibitor ... Conclusions: In this study, VK-2019 was well tolerated, exhibiting an excellent safety profile and exposure above in vitro efficacy. An MTD has ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-2814/751119/am/First-in-Human-clinical-trial-of-a-small-molecule

First-in-Human clinical trial of a small molecule EBNA1 ... Results: VK-2019 was well tolerated. One patient achieved a partial response. Pharmacokinetic results demonstrated good systemic exposure, with high ...

5. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/c/NCT04925544.html

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

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/5/815/751937/First-in-Human-Clinical-Trial-of-a-Small-Molecule

First-in-Human Clinical Trial of a Small-Molecule EBNA1 ... A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02830

VK 2019 for the Treatment of Epstein Barr Virus Positive ... This phase II trial tests whether VK-2019 works to shrink tumors in patients with Epstein Barr Virus (EBV) related nasopharyngeal carcinoma.

8. targetedonc.com targetedonc.com/view/new-study-explores-ebna1-as-a-target-for-epstein-barr-virus-positive-advanced-nasopharyngeal-carcinoma

New Study Explores EBNA1 as a Target for Epstein-Barr ... By targeting EBNA1, which has a unique protein fold and is present only in the cancer cells, we have so far observed fewer side effects than we ...