GPC3-targeted CAR T cell therapy for recurrent GPC3-positive glioblastoma

GPC-3 Chimeric Antigen Receptor T Cells FOR Recurrent GPC-3 Positive Glioblastoma

This study will try CAR T cells engineered to target GPC3 in adults with recurrent GPC3-positive glioblastoma during their planned surgery.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 21 Years to 70 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, CAR T, CART, chimeric antigen receptor, radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06815432 on ClinicalTrials.gov

What this trial studies

This phase 1 interventional protocol collects a patient’s blood to grow and genetically modify their T cells with a GPC3-directed chimeric antigen receptor and IL-15 using a retroviral vector, then cryopreserves the product. When the participant returns for planned repeat tumor resection, the engineered cells are thawed and given via intracavitary administration at the resection site and an Ommaya reservoir is placed for access. The protocol is a single-dose administration with standard premedication (acetaminophen and diphenhydramine) and focuses primarily on safety and feasibility in GPC3-expressing recurrent glioblastoma. Eligibility requires immunohistochemical confirmation of GPC3 expression and adequate performance status.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18 years) with recurrent glioblastoma scheduled for repeat resection whose tumor shows GPC3 expression (≥25% of tumor cells with moderate intensity) and who have a Karnofsky score ≥60%.

Not a fit: Patients whose tumors do not express GPC3, who have active uncontrolled infections, prior organ transplantation, known HIV positivity, or pre-existing anti-mouse antibodies are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, this approach could provide targeted killing of GPC3-positive tumor cells and potentially delay or reduce local recurrence after surgery.

How similar studies have performed: Related CAR T approaches have shown early signals of activity in some solid tumors and GPC3 CARs have been explored in liver cancer, but using GPC3-CAR T cells with IL-15 for glioblastoma is largely novel with limited human data.

Eligibility criteria

Procurement Inclusion Criteria:

* Diagnosis of GPC3-positive recurrent glioblastoma with previous resection planned for repeat resection.
* Age ≥18 years
* Karnofsky score ≥60%
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
* GPC3 expression (as determined by immunohistochemistry) with an extent score of ≥ Grade 2 (\>25% positive tumor cells) and an intensity score of ≥ 2 (scale 0-4).

Procurement Exclusion Criteria:

* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies).
* History of organ transplantation
* Known HIV positivity
* Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections).
* Exhibits other risk factors of which administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator

Treatment Inclusion Criteria:

* Age ≥ 18 years
* Diagnosis of recurrent glioblastoma with previous resection
* Karnofsky score ≥ 60%-
* Stable neurologic exam for 7 days prior to enrollment
* Stable or decreasing dose of steroids over past 7 days prior to surgery and administration of therapy (max allowable dose is 0.1mg/kg dexamethasone or equivalent per day)
* Adequate organ function:
* Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
* total bilirubin \< 3 times ULN for age
* INR ≤1.7
* absolute neutrophil count \> 500/μl
* platelet count \> 100,000/μl (can be transfused but must be achieved prior to enrollment)
* Hgb ≥ 7.0 g/dl (can be transfused)
* Pulse oximetry \>90% on room air
* Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Exclusion Criteria:

* Pregnancy or lactation
* Uncontrolled infection
* Known HIV positivity
* Active bacterial, fungal or viral infection
* History of organ transplantation
* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

Where this trial is running

Houston, Texas

• Baylor St. Luke's Medical Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Ganesh Rao, MD — Baylor College of Medicine
• Study coordinator: Ganesh Rao, MD

Conditions Glioblastoma Multiforme of Brain; GPC3-positive tumors; GPC3-CAR T cells; Glioblastoma; Brain Tumor