B-cell Acute Lymphoblastic Leukemia, Burkitt Lymphoma, Chronic Lymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, High-grade B-cell Lymphoma, Large B-cell Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Mixed Phenotype Acute Leukemia, Non Hodgkin Lymphoma, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Small Lymphocytic Lymphoma
Conditions
Keywords
CD19-positive, Leukemia, Lymphoma
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.
Interventions
GENETICDose Level 2, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETICDose Level 3, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETICDose Level 4, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
GENETICDose Level 1, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Sponsors
Vironexis Biotherapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 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
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment emergent adverse events (TEAEs) and treatment-emergent serious events (TESAEs) | Change from Baseline to Year 5 post dosing |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Contacts
CONTACTAllen Reha
CONTACTRecruitment Partner: PatientWing
STUDY_DIRECTORVironexis Clinical Trials
Vironexis Biotherapeutics Inc.
Outcome results
None listed