AAV dual-payload gene therapy injected directly into high-grade glioma to kill tumor cells and stimulate immune attack.
A Phase I/II Study of an AAV-1 Mediated Dual-Payload Gene Therapy in Patients With High Grade Glioma
This will try TGX-007, a virus-delivered gene therapy given into the tumor together with oral valaciclovir, in adults 18–70 with newly diagnosed or recurrent glioblastoma to see if it safely kills tumor cells and boosts immune response.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 68 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | Trogenix ltd Industry-sponsored |
| Locations | 2 sites (Columbus, Ohio and 1 other locations) |
| Trial ID | NCT07346144 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1/2, dose-finding and expansion trial of TGX-007, an AAV vector carrying two therapeutic genes (HSV-tk and IL-12) delivered by direct intratumoral injection. HSV-tk converts the oral prodrug valaciclovir into a cytotoxic agent to kill proliferating tumor cells, while IL-12 is intended to activate local anti-tumor immunity. The Phase 1 portion defines safety and an optimal biological dose, followed by further safety and preliminary efficacy assessment in Phase 2 in newly diagnosed or first-recurrence glioblastoma patients who are eligible for surgery. Patients receive the intratumoral injection at the time of indicated debulking surgery and then standard chemoradiotherapy or follow-up as appropriate.
Who should consider this trial
Good fit: Ideal candidates are adults 18–70 with Karnofsky performance status ≥70 who have unifocal unilateral high-grade glioma and are suitable for debulking surgery plus either standard chemoradiotherapy (newly diagnosed) or further surgery for first radiologic recurrence of GBM.
Not a fit: Patients with multifocal or bilateral tumors, poor functional status (KPS <70), multiple prior recurrences, contraindications to surgery, pregnancy, or significant organ dysfunction are unlikely to be eligible or to derive benefit from this approach.
Why it matters
Potential benefit: If successful, TGX-007 could both reduce tumor burden locally and prime the immune system to control or delay glioblastoma recurrence, potentially extending progression-free survival.
How similar studies have performed: Suicide-gene (HSV-tk) and cytokine gene therapies have been tested previously with mixed and limited success, and combining both payloads delivered by AAV in glioblastoma is a relatively novel approach without large definitive trials to date.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Aged 18-70 years * Karnofsky performance status ≥70 * Newly diagnosed patients: Unifocal, unilateral high-grade glioma based on MRI * Recurrent patients: First radiological progression (as determined by the multidisciplinary team \[MDT\]) of GBM previously treated with standard care surgery and chemoradiotherapy. Patients must have a prior confirmed histological/molecular diagnosis of GBM * Newly diagnosed patient: suitable for six weeks of chemoradiotherapy followed by six months of adjuvant temozolomide (Stupp protocol) * Debulking surgery is indicated for optimal patient care * Able to swallow oral medication * Willing to avoid live vaccines * Adequate organ function * Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to Day 0. * All patients must agree to practice true abstinence or to use highly effective contraception * Patient is willing and able to give informed consent for participation in the study Exclusion Criteria: * Patient who is pregnant, lactating or planning pregnancy during the course of the study * Immunodeficiency or active auto-immune disease requiring systemic therapy. * Active viral, bacterial or fungal infection requiring concurrent antivirals or antibiotics within 7 days of surgery * Live vaccine within 28 days prior to Day 0 * Use of immunosuppressant or immune modulatory medicines within 28 days prior to Day 0 * History of tuberculosis infection or chest x-ray or computed tomography (CT) chest showing radiological evidence of previous tuberculosis infection * Received previous treatment with a gene therapy * Significant history of a central nervous system disorder that, in the opinion of the Investigator, would preclude enrolment * Major surgery within 28 days prior to Day 0. A stereotactic biopsy is permitted * Known hypersensitivity or contraindications to valaciclovir, gadolinium, or any excipients for TGX-007 * Contraindication to MRI with gadolinium * Any condition expected to interfere with the intended timing of debulking surgery * Previous non-glioma cancer within 3 years (other than treated squamous/basal cell skin cancer, treated early-stage cervical cancer or treated/biochemically stable, organ confined prostate cancer) * Any other significant disease or disorder which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study * Patients who have participated in another research study involving an investigational product in the past 12 weeks or 5 half-lives of the product * Any psychological, familial, sociological, or geographical consideration potentially hampering compliance with the study protocol and follow up schedule; these conditions should be discussed with the patient before registration in the study * Unwilling to allow their general practitioner, if appropriate, to be notified of participation in the study Newly diagnosed patients only: * Any prior therapy for glioma * Intended use of tumour treating fields Recurrent patients only: * Prior toxicities from anti-cancer agents or radiotherapy which have not recovered to ≤Grade 1 severity * Intended use of tumour treating fields
Where this trial is running
Columbus, Ohio and 1 other locations
- Ohio State University Hospital — Columbus, Ohio, United States (Not_yet_recruiting)
- Royal Infirmary of Edinburgh — Edinburgh, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Project Management
- Email: Contact@trogenix.com
- Phone: +44131 287 5960
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.