HER2 Expressing Solid Tumors
Conditions
Keywords
HER2+ breast cancer, HER2+ gastric cancer, Other HER+ cancer, HER2-low cancer
Brief summary
This is a Phase 1/2, first-in-human, open-label, dose-escalating and expansion trial designed to assess the safety and efficacy of VNX-202 in patients with HER2 positive cancers.
Detailed description
VNX-202 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-HER2/anti-CD3 scFv diabody (termed GP202). GP202 binds to human epidermal growth factor receptor 2 (HER2) on the surface of cancer cells and to cluster of differentiation (CD)3 on the surface of T cells, inducing the T cells to kill the HER2-positive cancer cells. Following a single intravenous (IV) infusion, the vector induces the liver to continuously secrete GP202 into the bloodstream, resulting in long-term, consistent serum levels of GP202. Compared with conventionally delivered protein therapies, this gene therapy approach obviates the requirement for episodic dosing and avoids a possible reduction or loss of efficacy associated with trough levels of the protein between treatment cycles. 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 with previously treated metastatic HER2 solid tumors designed to determine the minimal dose that achieves target PK serum levels of GP202 at steady state (8-week timepoint) without dose-limited toxicities, defined as the recommended Part 2 dose (RP2D). Participants must have histologically or cytologically confirmed HER2 positive solid tumor cancers that has progressed during or following previous anti-cancer treatment. Part 2 (n=\ 15) 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-202 at the RP2D in a broader array of subjects. Part 2 will comprise of participants with early stage HER2-positive tumors who are at risk of disease relapse and/or metastasis despite having received prior systemic and/or local treatment. Each cohort will comprise ≥5 participants (Cohort A: breast cancer; Cohort B: gastric cancer; Cohort C: all otherHER2-positive tumor types). Patients will be followed for safety and efficacy up to 5 years post VNX-202 dosing.
Interventions
GENETICDose Level 1, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
GENETICDose Level 2, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
GENETICDose Level 3, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
GENETICDose Level 4, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
Sponsors
Vironexis Biotherapeutics Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age: ≥18 years of age * Histologically or cytologically confirmed diagnosis of HER-2 positive solid tumor as defined in the protocol * Part 1: presence of advanced or metastatic disease that has progressed during or following previous treatment * Part 2: Early stage HER-2 positive cancers with high risk for relapse following completion of SOC or after neoadjuvant systemic treatment * AAV specified capsid total antibody ≤1:400 * ECOG performance status of 0 or 1 * Life expectancy ≥3 months * 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) * Known active CNS or leptomeningeal disease * History of thrombotic microangiopathy or cardiomyopathy, or evidence of sensory neuropathy * Pregnant or nursing (lactating) women * History of other malignancy within 5 years prior to screening as defined in protocol * History of hypersensitivity to corticosteroids or history of corticosteroid-related toxicity Concurrent anti-cancer treatment in another investigational trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) | Change from Baseline to Year 5 post dosing |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in T cell subsets and clonality | Change from baseline to year 5 post dosing |
| Change from baseline in ctDNA | Change from baseline to year 5 post dosing |
| Change from baseline in progression free survival | Change from baseline to year 5 post dosing |
| Change from baseline in overall survival | Change from baseline to year 5 post dosing |
Countries
United States
Contacts
CONTACTAllen Reha
Outcome results
None listed