Clinical trial NCT06533579: Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)
Official title: A Phase 1/2 Safety, Dose-finding, and Pharmacokinetics Study of VNX-101 Gene Therapy in Patients With Relapsed or Refractory CD19-Positive Hematologic Malignancies (SENTRY-CD19)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Large B-cell Lymphoma
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Marginal Zone Lymphoma
Follicular Lymphoma
Mantle Cell Lymphoma
Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
Burkitt Lymphoma
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Non Hodgkin Lymphoma
Mixed Phenotype Acute Leukemia
Keywords: CD19-positive
Leukemia
Lymphoma
Lead sponsor: Vironexis Biotherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 32
Sex: ALL
Minimum age (years): 13
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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/Exclusion criteria to be applied per protocol.

Primary outcomes:
measure: Treatment emergent adverse events (TEAEs) and treatment-emergent serious events (TESAEs)
timeFrame: Change from Baseline to Year 5 post dosing
Secondary outcomes:
measure: Change from baseline in B-cell counts
timeFrame: Change from baseline to year 5 post dosing
measure: Change baseline in immunoglobulin levels
timeFrame: Change from baseline to year 5 post dosing
measure: Change baseline in antitumor activity
timeFrame: Change from baseline to year 5 post dosing
measure: Proportion/duration of subjects achieving response, progression free survival, and disease free survival.
timeFrame: Change from baseline to year 5 post dosing
Other outcomes:
measure: Exploratory Measure: Change in VNX-101 gene product levels
timeFrame: Change from baseline to year 5 post dosing
measure: Exploratory Measure: Change in VNX-101 vector shedding
timeFrame: Change from baseline to year 5 post dosing
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Nashville
country: United States
facility: TriStar BMT
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Vironexis Biotherapeutics Inc.
name: Vironexis Clinical Trials
role: STUDY_DIRECTOR
References: