Gene Therapy for HER-Positive Cancer (SENTRY-HER2)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Dose Level 1, VNX-202, Dose Level 2, VNX-202, Dose Level 3, VNX-202, Dose Level 4, VNX-202.
- Who it may be relevant to
- Registry conditions: HER2 Expressing Solid Tumors. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 1/2, First-in-Human Study of VNX-202 Gene Therapy in Patients With HER2-Positive Cancer
Overview
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
- Genetic Dose Level 1, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion - Genetic Dose Level 2, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion - Genetic Dose Level 3, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion - Genetic Dose Level 4, VNX-202
Adeno-associated viral vector encoding the CD3/HER2 Bi-Specific T-Cell Engager (AAV.CD3/HER2), Single IV Infusion
Primary outcome measures
- Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) [Time frame: Change from Baseline to Year 5 post dosing]
Secondary outcome measures (4)
- 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]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 11 centers
- Valkyrie Clinical Trials — Los Angeles
- SCRI Denver DDU at HealthOne — Denver
- Mayo Clinic — Jacksonville
- Mayo Clinic — Rochester
- Hackensack Medical Center — Hackensack
- Memorial Sloan Kettering Cancer Center — New York
- Cleveland Clinic — Cleveland
- Thomas Jefferson University, Sidney Kimmel Cancer Center — Philadelphia
- … and 3 more centers
Identifiers
NCT: NCT07192432 · VNX-202-01