Gene Therapy for HER-Positive Cancer (SENTRY-HER2)

Not Applicable

Not yet recruiting

• Conditions: HER2 Expressing Solid Tumors

• Registration Number: NCT07192432
• Lead Sponsor: Vironexis Biotherapeutics Inc.

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.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-17
• Study First Submitted QC: 2025-09-17
• Last Update Submitted: 2025-09-17
• Study First Posted: 2025-09-25
• Last Update Posted: 2025-09-25
• Study Start: 2025-11-01
• Primary Completion: 2033-09
• Study Completion: 2033-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 27

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)	Change from Baseline to Year 5 post dosing

Secondary Outcome Measures

Name	Time	Method
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
Change from baseline in T cell subsets and clonality	Change from baseline to year 5 post dosing