VK-2019 for adults with relapsed or refractory EBV-positive diffuse large B‑cell lymphoma

A Phase Ib Study of VK-2019 in Patients With Relapsed or Refractory EBV+ Diffuse Large B-cell Lymphomas (DLBCL)

This trial tests daily oral VK-2019 in adults with relapsed or refractory EBV-positive DLBCL to see if it is safe and can control the disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Thomas Jefferson University (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06789159 on ClinicalTrials.gov

What this trial studies

This is an open-label phase Ib dose-escalation trial testing single-agent VK-2019 given orally daily in 28-day cycles with three dose cohorts (600 mg, 1200 mg, 1800 mg). Patients will have response assessments every three cycles and those with at least stable disease after three cycles may continue treatment. The primary focus is safety and tolerability, with biomarker assessments included to explore activity in EBV-positive tumors. All patients will be followed for survival for up to three years.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory EBV-positive DLBCL who have had at least two prior systemic regimens, exhausted standard options, have measurable disease, ECOG ≤2, and adequate organ function are the intended participants.

Not a fit: Patients with EBV-negative DLBCL, poor performance status (ECOG >2), inadequate organ function, pregnancy, or those who progress early during treatment are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, VK-2019 could offer an oral treatment option that controls EBV-positive relapsed/refractory DLBCL with manageable side effects.

How similar studies have performed: This is a relatively novel single-agent approach for EBV-positive DLBCL—other early-phase EBV-targeting and oral targeted therapies have shown limited promise in small studies but definitive success in this specific setting is unproven.

Eligibility criteria

4.1 Inclusion Criteria

1. Informed consent obtained prior to any protocol mandated assessment.
2. Age ≥ 18 years.
3. Patient must have relapsed or refractory EBV-positive DLBCL after a minimum of 2 prior regimens of systemic therapy.
4. Patient must have exhausted all available standard of care treatment options that could potentially provide clinical benefit.
5. Toxicities related to prior therapy must have returned to Grade 1 or less, or if chronic must be stable. Peripheral neuropathy must be Grade 2 or less
6. Prior anti-cancer treatment must have been completed greater than 2 weeks prior to study day 1.
7. Patients must have measurable disease, as defined by IWG 2007 criteria.
8. ECOG performance status score of ≤2
9. Adequate organ function as defined by the following criteria:

   1. Absolute neutrophil count \> 1,500/microl (stable off any growth factor within 1 week of study drug administration)
   2. Hemoglobin \> 9 g/dL (transfusion to achieve this level is permitted)
   3. Platelet count \> 75,000/microl (transfusion to achieve this level is NOT permitted)
   4. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN);
   5. Total serum bilirubin ≤ 1.5 x ULN;
   6. Creatinine clearance≥ 60 ml/min as calculated per Cockcroft and Gault equation.
   7. 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;
10. Sexually active patients will 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. See Protocol Appendix C.
11. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

4.2 Exclusion Criteria

1. Patients with 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; patents with effectively treated conditions (e.g. stenting for CAD) are eligible.
2. Patients with metastatic disease with active central nervous system (CNS) involvement, defined as parenchymal brain or leptomeningeal involvement.
3. Concurrent administration of herbal preparations.
4. A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
5. Patients currently taking drugs that inhibit or induce OATP1B1 or OATP1B3 within 5 half- lives of that agent. Examples are included in Appendix B.
6. Patients currently taking drugs that are proton pump inhibitors (PPIs) within 5 half- lives of that agent. Examples are included in Appendix B.
7. Patients who have received a prior organ allograft or allogeneic bone marrow transplant are eligible but must have no evidence of active GVHD and be off immunosuppressive drugs.
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. Patients with corrected QT by Fridericia's formula (QTcF) of \>470 ms are excluded.
13. Patients with Post-Transplant Lymphoproliferative Disease (PTLD) are excluded.

Where this trial is running

Philadelphia, Pennsylvania

• Honickman Center — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Michael S Wysota, MD — Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
• Study coordinator: Michael S Wysota, MD

Conditions Diffuse Large B Cell Lymphoma Refractory; Diffuse Large B Cell Lymphoma Relapsed; Epstein-Barr Virus Infection