Using CAR-T cells to target B7-H3 in recurrent glioblastoma

Phase I Study of Intraventricular Infusion of T Cells Expressing B7-H3 Specific Chimeric Antigen Receptors (CAR) in Subjects With Recurrent or Refractory Glioblastoma

This study is testing a new CAR-T cell therapy that targets a specific protein in patients with recurrent glioblastoma to see if it's safe and how much can be given.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: UNC Lineberger Comprehensive Cancer Center (other)
• Drugs / interventions: bevacizumab, chimeric antigen receptor, radiation, CAR-T, Immunotherapy
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT05366179 on ClinicalTrials.gov

What this trial studies

This phase 1 clinical trial aims to evaluate the safety of CAR-T cell therapy targeting the B7-H3 antigen in patients with recurrent or refractory glioblastoma multiforme (GBM). Participants will undergo a procedure to collect their T cells, which will then be modified to create CAR.B7-H3T cells. These modified cells will be infused into patients via intraventricular infusion, with up to three weekly doses administered. The study will also determine the maximum tolerated dose and the recommended dose for future studies based on safety and feasibility.

Who should consider this trial

Good fit: Ideal candidates are adults with recurrent or refractory glioblastoma who have previously undergone surgical resection and meet specific eligibility criteria.

Not a fit: Patients with disseminated GBM down the spinal cord or those who have received antiangiogenic agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with recurrent glioblastoma, potentially improving survival outcomes.

How similar studies have performed: While CAR-T cell therapies have shown promise in other cancers, this specific approach targeting B7-H3 in glioblastoma is novel and has not been previously tested in humans.

Eligibility criteria

INCLUSION CRITERIA

1. Karnofsky score of \> 60%
2. Diagnosis or recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021) based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis.
3. Must have undergone at least 4005 cGy of radiation with concurrent temozolomide.
4. No current or previous exposure to antiangiogenic agents, such as bevacizumab.
5. Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation.
6. Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the cell infusion therapy. If a male subject receives multiple infusions, they must remain on contraception throughout the duration and 3 months after the last cell infusion therapy.
7. The subject is willing and able to comply with study procedures based on the judgment of the investigator.

EXCLUSION CRITERIA

1. Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).
2. Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
3. Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load.
4. Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.
5. Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma.
6. Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord.
7. Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.

Where this trial is running

Chapel Hill, North Carolina

• Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Felicia Cao, MD, PhD — UNC Lineberger Comprehensive Cancer Center
• Study coordinator: Catherine Cheng

Conditions: Glioblastoma Multiforme, Brain Tumor, Cell therapy, Relapse, Recurrent