Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)
- Conditions
- B-cell Acute Lymphoblastic LeukemiaLarge B-cell LymphomaChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMarginal Zone LymphomaFollicular LymphomaMantle Cell LymphomaDiffuse Large B Cell LymphomaHigh-grade B-cell LymphomaBurkitt Lymphoma
- Interventions
- Genetic: Dose Level 1, VNX-101Genetic: Dose Level 2, VNX-101Genetic: Dose Level 3, VNX-101Genetic: Dose Level 4, VNX-101
- Registration Number
- NCT06533579
- Lead Sponsor
- Vironexis Biotherapeutics Inc.
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 32
- Age: Part 1: 18-90 years of age, Part 2: 13-90 years of age
- Relapsed or refractory CD-19 positive leukemia or lymphoma as defined in the protocol
- CD19-positive expression
- AAV specified capsid total antibody <1:400
- Protocol-specified ranges for renal, liver, cardiac and pulmonary function
- Protocol-specified ranges for hematology parameters
- Hepatoxicity (AST or ALT > 2x upper limit of normal)
- History of thrombotic microangiopathy or cardiomyopathy, or evidence of sensory neuropathy
- Pregnant or nursing (lactating) women
- Acute Graft versus Host Disease (GvHD): Grade 2-4 or chronic GvHD of any grade
- History of hypersensitivity to corticosteroids or history of corticosteroid-related toxicity
- Chemotherapy given within the protocol-specified discontinuation timelines
Other Inclusion/Exclusion criteria to be applied per protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group 1/Group 2/Group 3/Group 4 Dose Level 3, VNX-101 - Group 1/Group 2/Group 3/Group 4 Dose Level 2, VNX-101 - Group 1/Group 2/Group 3/Group 4 Dose Level 4, VNX-101 - Group 1/Group 2/Group 3/Group 4 Dose Level 1, VNX-101 -
- Primary Outcome Measures
Name Time Method Treatment emergent adverse events (TEAEs) and treatment-emergent serious events (TESAEs) Change from Baseline to Year 5 post dosing
- Secondary Outcome Measures
Name Time Method Change from baseline in B-cell counts Change from baseline to year 5 post dosing Change baseline in immunoglobulin levels Change from baseline to year 5 post dosing Change baseline in antitumor activity Change from baseline to year 5 post dosing Proportion/duration of subjects achieving response, progression free survival, and disease free survival. Change from baseline to year 5 post dosing
Trial Locations
- Locations (6)
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
TriStar BMT
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States