Gene Therapy for B-Cell Acute Lymphoblastic Leukemia
Sponsor: Vironexis Biotherapeutics Inc.
ClinicalTrials ID:NCT06533579
This Phase 1/2 trial evaluates VNX-101, an AAV gene therapy, in relapsed/refractory CD19+ B-cell ALL. It involves dose-escalation to determine safety and efficacy. Eligibility includes ages 13-90, specific marrow blast levels, and prior CAR-T ineligibility. Interventions include four dose levels of a single IV infusion of VNX-101, a CD3/CD19 Bi-Specific T-Cell Engager.
Patient Parameters
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Program Overview
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+ B-cell acute lymphoblastic leukemia (ALL).
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 with marrow blasts <5%) will be used determine the dose for Part 2 in patients at higher disease burden (marrow blasts <50%). 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=~14) 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 with higher leukemic burden (i.e. bone marrow blasts <50%). 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.
Eligibility Criteria
Inclusion Criteria
- Age: Part 1: 18-90 years of age, Part 2: 13-90 years of age
- Relapsed B-cell ALL with bone marrow blasts >= 5%
- Refractory B-cell ALL as defined in the protocol
- Bone marrow blasts requirement (flow cytometry): Part 1: >0.01% to <5% prior to VNX-101 dosing, Part 2: >0.01% to <50% prior to VNX-101 dosing.
- Ineligible or declined CAR-T therapy or failed to respond or relapsed after such therapy
- If prior blinatumomab treatment, cells remain CD19+ and not refractory to blinatumomab
- AAV specified capsid total antibody <1:400
- Protocol-specified ranges for renal, liver, cardiac and pulmonary function
- Protocol-specified ranges for hematology parameters
Exclusion Criteria
- 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.
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Colorado Blood Cancer Institute | 80218 | Denver | Colorado |
| Oncology Hematology Care | 45242 | Cincinnati | Ohio |
| The Ohio State University Wexner Medical Center | 43210 | Columbus | Ohio |
| TriStar BMT | 37203 | Nashville | Tennessee |
| University of Texas MD Anderson Cancer Center | 77030 | Houston | Texas |
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