VK-2019 for Lymphoma

Recruiting at 1 trial location

Overseen By Michael S Wysota, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Jefferson University

Must not be taking: Herbal preparations, PPIs, OATP1B1/3 drugs

Disqualifiers: Cardiopulmonary diseases, CNS involvement, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle, until progression or toxicity

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, VK-2019 (experimental treatment), for individuals with EBV-positive DLBCL, a type of lymphoma that hasn't responded to other treatments. The goal is to determine if daily doses of VK-2019 can benefit these patients by testing different dosages. It seeks participants who have tried at least two other therapies without success and have no other standard treatment options available. As a Phase 1 trial, this research focuses on understanding how VK-2019 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those that inhibit or induce OATP1B1 or OATP1B3, and proton pump inhibitors (PPIs), within 5 half-lives of those agents. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

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

Research has shown that VK-2019 is generally safe for people. In previous studies, patients taking up to 1800 mg daily mostly experienced mild to moderate side effects. Common side effects included mild headaches or slight tiredness, which were not severe. Most participants tolerated the treatment well, without serious problems. This makes it a promising option for those considering joining the trial. ^{1 2 3 4 5}

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

Researchers are excited about VK-2019 for lymphoma because it offers a new approach by potentially targeting cancer cells more precisely. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, VK-2019 is designed to focus specifically on the cancer cells, possibly reducing side effects. This treatment is being tested in three different dosages—600mg, 1200mg, and 1800mg—to find the most effective balance of potency and safety. If successful, VK-2019 could provide a more targeted and less toxic treatment option for lymphoma patients.

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

Research has shown that VK-2019 holds promise for treating certain types of lymphoma. Early studies found that patients tolerated VK-2019 well and that it remained in the body long enough to potentially be effective. In these studies, one patient experienced a partial response, meaning their cancer shrank but did not completely disappear. VK-2019 targets a protein called Epstein-Barr nuclear antigen 1, which helps stop the virus from multiplying. This action might prevent cancer cells linked to the virus from growing and spreading. While more research is needed, these findings suggest that VK-2019 could be a helpful treatment option for lymphoma related to this virus. Participants in this trial will receive VK-2019 at different dosages to evaluate its effectiveness and safety. ^{1 4 6 7 8}

Who Is on the Research Team?

Michael S Wysota, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults with EBV-positive DLBCL, a type of lymphoma, who have tried other treatments that didn't work. Participants will take an oral medication daily in increasing doses to find the right balance between effectiveness and safety.

Inclusion Criteria

4.1 Inclusion Criteria

1. Informed consent obtained prior to any protocol mandated assessment.

3. Patient must have relapsed or refractory EBV-positive DLBCL after a minimum of 2 prior regimens of systemic therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral dosing of VK-2019 in three dose escalation cohorts for 28-day cycles

28 days per cycle, until progression or toxicity

Response assessment every 3 cycles

Follow-up

Participants are monitored for survival and safety after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• VK-2019

Trial Overview VK-2019 is being tested at three different strengths (600 mg, 1200 mg, and 1800 mg) taken once a day for cycles of 28 days. The goal is to see how well it works and what dose is best for people whose lymphoma has come back or hasn't responded to treatment.

How Is the Trial Designed?

Group I: Treatment (VK-2019 Dose 600mg) Experimental Treatment 1 Intervention

Dose cohort A will dose at 600mg. VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort A will dose at 600 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Group II: Treatment (VK-2019 Dose 1800mg) Experimental Treatment 1 Intervention

Dose cohort C will dose at 1800mg. VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort C will dose at 1800 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Group III: Treatment (VK-2019 Dose 1200mg) Experimental Treatment 1 Intervention

Dose cohort B will dose at 1200mg.VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort B will dose at 1200 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

The Wistar Institute

Collaborator

Trials

10

Recruited

790+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 1790 patients with extranodal NK/T-cell lymphoma, achieving progression-free survival at 24 months (PFS24) was associated with significantly better overall survival (OS), with a 5-year OS rate of 92.2% compared to only 19.2% for those who did not achieve PFS24.

The findings suggest that PFS24 can serve as an important early endpoint for evaluating treatment success and risk stratification in ENKTCL, indicating that patients who maintain PFS24 have excellent long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study. Yang, Y., Wang, Y., Liu, X., et al.[2021]

In a study involving 21 patients with relapsed or refractory non-Hodgkin lymphoma, apatinib demonstrated a promising overall response rate of 47.6%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, including proteinuria and hypertension, suggesting that apatinib could be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. Li, L., Xiao, S., Zhang, L., et al.[2022]

In a review of 2225 lymphoma patients from 4 randomized controlled trials, brentuximab vedotin was found to significantly increase the risk of all-grade adverse events (AEs) and high-grade AEs compared to non-brentuximab vedotin treatments.

Specific AEs associated with brentuximab vedotin included a higher risk of peripheral sensory neuropathy, pyrexia, nausea, vomiting, diarrhea, and alopecia, with particularly high risks for high-grade sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Gao, S., Zhang, M., Wu, K., et al.[2021]

Recent advancements in treating diffuse large B cell lymphoma have led to improved patient outcomes, particularly through dose-dense chemotherapy regimens and the combination of rituximab with chemotherapy, resulting in higher response rates and longer survival.

While low-risk patients have seen significant improvements, high-risk patients still require more effective strategies, potentially through better understanding of genetic factors that contribute to treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies for the treatment of diffuse large B cell lymphoma. Coiffier, B.[2019]

In a post-marketing surveillance study of 284 Japanese patients with relapsed/refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin demonstrated an acceptable safety profile, with 74.3% of patients experiencing adverse drug reactions.

Common adverse reactions included peripheral sensory neuropathy and neutropenia, with some patients experiencing severe reactions and a few fatal cases, highlighting the need for careful monitoring, particularly for pulmonary toxicity in at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of brentuximab vedotin in Japanese patients with relapsed/refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma: a post-marketing surveillance study. Izutsu, K., Ogura, M., Tobinai, K., et al.[2021]

New-generation Bruton tyrosine kinase inhibitors (BTKi) show a high overall response rate of 92% in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), particularly benefiting younger patients and those receiving combination therapy.

While BTKi-based therapies are generally well-tolerated, they can lead to significant adverse events like cytopenia and hypertension, and zanubrutinib may offer better efficacy than acalabrutinib as a monotherapy for CLL/SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. Yin, S., Zheng, X., Zhang, W., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06789159

A Phase Ib Study of VK-2019 in Patients With Relapsed or ... This is an open label, dose-escalation phase Ib study with biomarker assessments to determine the safety and tolerability of single agent VK-2019 in patients ...

2. 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 ...

3. 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 ... Results: VK-2019 was well tolerated. One patient achieved a partial response. Pharmacokinetic results demonstrated good systemic exposure, with high ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-10500

VK-2019 for the Treatment of Patients with Relapsed or ... VK-2019 works by attaching to Epstein-Barr nuclear antigen 1 and blocking the virus from replicating and may prevent the cancer cells from growing and spreading ...

5. trial.medpath.com trial.medpath.com/clinical-trial/6a3ebba2f2d7a91d/nct06789159-vk-2019-ebv-dlbcl-study

A Phase Ib Study of VK-2019 in Patients With Relapsed or ... This is a Phase Ib in adult patients with relapsed or refractory EBV-positive DLBCL using daily oral dosing of VK-2019 in three dose escalation cohorts: 600 mg ...

6. 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 ...

7. medchemexpress.com medchemexpress.com/vk-2019.html?srsltid=AfmBOoo2HWIi3msNL8v3RsZoCzGdk5vtC713qQvI8guR2iYmkhfgHZEx

VK-2019 | EBNA1 Inhibitor VK-2019 is an oral active, selective EBNA1((Epstein-Barr Nuclear Antigen 1) inhibitor and can be used for study of EBV-associated carcinomas.

8. wistar.org wistar.org/press-releases/wistar-and-stanford-medicine-to-begin-phase-2-clinical-trial-of-vk-2019-in-patients-with-epstein-barr-virus-ebv-positive-advanced-nasopharyngeal-carcinoma/

Wistar and Stanford Medicine to Begin Phase 2 Clinical ... The open-label, single-group Phase 2 clinical trial will assess the safety and efficacy of VK-2019. Enrollment is expected to begin later ...