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

Vironexis Biotherapeutics Inc.

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

HER2 Expressing Solid Tumors

Treatments

Genetic: Dose Level 2, VNX-202

Genetic: Dose Level 3, VNX-202

Genetic: Dose Level 1, VNX-202

Genetic: Dose Level 4, VNX-202

Study type

Interventional

Funder types

Industry

Identifiers

NCT07192432

VNX-202-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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