Gene Therapy for B-Cell Acute Lymphoblastic Leukemia

Vironexis Biotherapeutics Inc.

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

B-cell Acute Lymphoblastic Leukemia

Treatments

Genetic: Dose Level 4, VNX-101

Genetic: Dose Level 3, VNX-101

Genetic: Dose Level 2, VNX-101

Genetic: Dose Level 1, VNX-101

Study type

Interventional

Funder types

Industry

Identifiers

NCT06533579

VNX-101-01

Details and patient eligibility

About

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).

Full 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.

Enrollment

26 estimated patients

Sex

All

Ages

13 to 90 years old

Volunteers

No Healthy Volunteers

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.