NCT07192432

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

A Phase 1/2, First-in-Human Study of VNX-202 Gene Therapy in Patients With HER2-Positive Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Vironexis Biotherapeutics Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• HER2 Expressing Solid Tumors

Interventions

Type	Name	Description
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

Timeline

• Start date: 2025-11-18
• Primary completion: 2033-09-01
• Completion: 2033-10-01
• First posted: 2025-09-25
• Last updated: 2026-04-01

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study