Gene Therapy for B-Cell Acute Lymphoblastic Leukemia

Phase 1

Recruiting

• Conditions: B-cell Acute Lymphoblastic Leukemia
• Interventions: Genetic: Dose Level 1, VNX-101; Genetic: Dose Level 2, VNX-101; Genetic: Dose Level 3, VNX-101; Genetic: 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+ B-cell acute lymphoblastic leukemia (ALL).

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 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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2024-07-24
• Study First Submitted QC: 2024-07-29
• Study First Posted: 2024-08-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-10
• Study Start: 2024-12-30
• Primary Completion: 2026-06
• Study Completion: 2031-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 26

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

Read More

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.

Read More

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
Proportion/duration of subjects achieving hematological response, progression free survival, and disease free survival.	Change from baseline to year 5 post dosing
Change baseline in antitumor activity	Change from baseline to year 5 post dosing

Trial Locations

Locations (3)

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Oncology Hematology Care; 🇺🇸 Cincinnati, Ohio, United States

TriStar BMT; 🇺🇸 Nashville, Tennessee, United States