NCT06533579

Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)

A Phase 1/2 Safety, Dose-finding, and Pharmacokinetics Study of VNX-101 Gene Therapy in Patients With Relapsed or Refractory CD19-Positive Hematologic Malignancies (SENTRY-CD19)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: Vironexis Biotherapeutics Inc. · Industry
• Sex: All
• Age: 13 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, first-in-human, open-label, dose-escalating trial designed to assess the safety and efficacy of VNX-101 in patients with relapsed or refractory CD19-positive hematologic malignancies.

Detailed description

VNX-101 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-CD19/anti-CD3 scFv diabody (termed GP101). GP101 binds both cluster of differentiation (CD)19 and CD3, inducing T-cells to kill both benign and malignant B-cells. Following a single intravenous (IV) infusion, the vector induces the liver and key tissues to continuously secrete GP101 into the bloodstream, resulting in long-term, consistent serum levels of GP101. Potential advantages of VNX-101 over autologous CAR-T therapy include it is off-the-shelf, provides a gentle onset of action, does not require lymphodepletion chemotherapy, engages all T-cells continuously (including those freshly produced from the bone marrow), and utilizes highly efficient signaling through the native T-cell receptor. In this 2-part study, dose-finding data from Part 1 of the study (n=\~12 patients) will be used determine the dose for Part 2 in patients. Part 1 is a dose-finding PK study in adults ≥18 years old designed to determine the minimal dose that achieves target PK serum levels of GP101 at steady state (8-week timepoint) without dose-limited toxicities, defined as the recommended Part 2 dose (RP2D). Prior to VNX-101 dosing, subjects may undergo standard of care chemotherapy to meet dosing criteria. Part 2 (n=\~20) will be opened following data safety monitoring board review of Part 1 data and is designed to determine the safety and pharmacokinetics (PK) of VNX-101 at the RP2D in a broader array of subjects. The age range for Part 2 will be expanded to include subjects ≥13 years old. Patients will be followed for safety and efficacy up to 5 years post VNX-101 dosing. Long-term follow-up assessments for safety will be conducted for 6 to 15 years post VNX-101 dosing.

Conditions

• B-cell Acute Lymphoblastic Leukemia
• Large B-cell Lymphoma
• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Marginal Zone Lymphoma
• Follicular Lymphoma
• Mantle Cell Lymphoma
• Diffuse Large B Cell Lymphoma
• High-grade B-cell Lymphoma
• Burkitt Lymphoma
• Primary Mediastinal Large B-cell Lymphoma (PMBCL)
• Non Hodgkin Lymphoma
• Mixed Phenotype Acute Leukemia

Interventions

Type	Name	Description
GENETIC	Dose Level 1, VNX-101	Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETIC	Dose Level 2, VNX-101	Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETIC	Dose Level 3, VNX-101	Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETIC	Dose Level 4, VNX-101	Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion

Timeline

• Start date: 2025-05-30
• Primary completion: 2027-06-01
• Completion: 2031-09-01
• First posted: 2024-08-01
• Last updated: 2026-03-30

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study