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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
Valkyrie Clinical Trials
Los Angeles, California, United States
RECRUITINGSCRI Denver DDU at HealthOne
Denver, Colorado, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGTreatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)
Time frame: Change from Baseline to Year 5 post dosing
Change from baseline in T cell subsets and clonality
Time frame: Change from baseline to year 5 post dosing
Change from baseline in ctDNA
Time frame: Change from baseline to year 5 post dosing
Change from baseline in progression free survival
Time frame: Change from baseline to year 5 post dosing
Change from baseline in overall survival
Time frame: Change from baseline to year 5 post dosing
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Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion