CAR-T Cell Therapy for Glioblastoma

Overseen By Yasmeen Rauf, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Radiation, Temozolomide

Must not be taking: Antiangiogenic agents

Disqualifiers: Pregnancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR.B7-H3T cells, a type of CAR-T cell therapy, for individuals with glioblastoma, an aggressive brain cancer. The trial aims to determine if this treatment is safe for human use. Participants must have glioblastoma that has recurred or is resistant to other treatments and must have already received a specific type and amount of radiation and chemotherapy. The trial seeks individuals who have not yet tried certain other cancer drugs and who can undergo MRI scans. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must not have had previous exposure to certain treatments like antiangiogenic agents or chimeric antigen receptor T cell therapy for glioblastoma.

Is there any evidence suggesting that CAR.B7-H3T cells are likely to be safe for humans?

Research shows that CAR.B7-H3T cells have not been tested in humans, so direct safety information for this treatment in people is unavailable. This Phase 1 trial marks the first step in testing the treatment in humans, focusing primarily on safety and side effects. Researchers typically begin with low doses to assess how well participants tolerate the treatment and to monitor for any adverse effects.

Although the B7-H3 target has been studied in labs and its potential for treating tumors has been explored, real-world data from humans is still needed. Since the FDA has not yet approved CAR.B7-H3T cells for glioblastoma, this trial is crucial for understanding the safety and tolerability of this treatment. Participants will be closely monitored to gather this vital information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CAR.B7-H3 T cell therapy because it offers a novel approach to tackling glioblastoma, a notoriously aggressive brain tumor. Unlike standard treatments like surgery, radiation, and chemotherapy that aim to remove or shrink the tumor, CAR-T cell therapy works by genetically engineering a patient's own immune cells to specifically target and attack cancer cells. This therapy is unique because it targets the B7-H3 protein, which is often overexpressed in glioblastoma cells, potentially leading to a more precise and effective treatment. This targeted approach not only promises to enhance treatment efficacy but also has the potential to minimize damage to healthy brain tissue, which is a significant challenge with current treatment options.

What evidence suggests that CAR.B7-H3T cells might be an effective treatment for glioblastoma?

Research shows that a new cell therapy called CAR.B7-H3T might help treat glioblastoma, a type of brain cancer. These special cells can locate and attack a protein called B7-H3, found on cancer cells. Early lab studies suggest that these cells effectively kill cancer cells taken from patients, indicating potential benefits for those with this aggressive brain cancer. Although this treatment is not yet approved for human use, early results are promising. Participants in this trial will receive CAR.B7-H3T cells to evaluate their effectiveness and safety in treating glioblastoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Yasmeen Rauf

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma who've had radiation and temozolomide treatment, but no antiangiogenic agents like bevacizumab. They must not have widespread disease down the spinal cord or previous CAR-T therapy, and should be able to follow study procedures. Women of childbearing age and men with partners must agree to use contraception.

Inclusion Criteria

I am a male and will use birth control during and for 3 months after my treatment.

I have never been treated with drugs that stop the formation of blood vessels in cancer.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials.

My cancer has spread to my brainstem, cerebellum, or spinal cord.

Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Collection and Manufacturing

Cells are collected following initial surgical resection to manufacture CAR.B7-H3T cells, preferably before initiation of adjuvant chemoradiation

4 weeks

Treatment

Eligible subjects receive up to 3 weekly infusions of CAR.B7-H3 cells

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events, cytokine release syndrome, and neurotoxicity

10 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• CAR.B7-H3T cells

Trial Overview The trial is testing a new potential treatment called CAR.B7-H3T cells infusion for glioblastoma patients. This involves modifying T cells to target cancer cells more effectively. It's an early-stage trial focusing on safety since this approach hasn't been tried in humans before.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

CAR.B7-H3 T cells: Subjects with refractory or recurrent glioblastoma multiforme, have cells collected following their initial surgical resection to manufacture CAR.B7-H3 T cells, preferably before initiation of adjuvant chemoradiation.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) T cell therapy shows promise for treating glioblastoma, with initial studies indicating an acceptable safety profile, but the antitumor effects have not met expectations due to challenges like tumor heterogeneity and an immunosuppressive environment.

Ongoing research is exploring novel target antigens and combinations with other therapies to enhance the effectiveness of CAR T cells in glioblastoma, suggesting potential for improved clinical outcomes as our understanding of the disease and CAR technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells for Glioblastoma: Current Concepts, Challenges, and Future Perspectives. Karschnia, P., Teske, N., Thon, N., et al.[2021]

B7-H3 is frequently overexpressed in glioblastoma (GBM) and correlates with higher malignancy and poorer survival rates, making it a promising target for treatment.

CAR T cells engineered to target B7-H3 showed significant antitumor effects in both laboratory tests and in animal models, leading to longer survival compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. Tang, X., Zhao, S., Zhang, Y., et al.[2020]

In a first-in-human trial of EGFRvIII-directed CAR T cell therapy for recurrent glioblastoma, the presence of PD1 expression in CD4+ CAR T cells was found to positively correlate with both engraftment in the bloodstream and progression-free survival (PFS).

The study suggests that PD1+ CAR T cells may serve as a predictive marker for therapeutic success in solid tumors, as higher frequencies of PD1+GZMB+ and PD1+HLA-DR+ CAR T cells were associated with better clinical outcomes, while other immune checkpoint markers did not show significant associations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD1 Expression in EGFRvIII-Directed CAR T Cell Infusion Product for Glioblastoma Is Associated with Clinical Response. Tang, OY., Tian, L., Yoder, T., et al.[2022]

CAR T-cell therapy shows promise in treating glioblastoma, a highly aggressive brain tumor, but faces challenges due to the tumor's complexity and immunosuppressive environment.

Ongoing research is focused on improving CAR T-cell efficacy through novel targets, T-cell modifications, and combination therapies, alongside the development of better preclinical models to enhance clinical trial outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Glioblastoma-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy. Salinas, RD., Durgin, JS., O'Rourke, DM.[2021]

CAR T-cell therapy, which involves modifying a patient's own T cells to target cancer cells, has shown promising safety and feasibility in treating glioblastoma, a type of brain cancer, despite the challenges associated with this disease.

Some patients with glioblastoma have experienced signs of efficacy from CAR T-cell therapy, indicating potential for this treatment approach, even though significant barriers to effective T-cell function remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. Bagley, SJ., Desai, AS., Linette, GP., et al.[2019]

Infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells in eight patients with GD2-positive glioblastoma (GBM) was found to be safe and well tolerated, with no severe adverse events reported.

Of the eight patients, four experienced a partial response lasting between 3 to 24 months, indicating that 4SCAR-T cells can exert anti-GBM activity, with a median overall survival of 10 months post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Liu, Z., Zhou, J., Yang, X., et al.[2023]

CAR T-cell therapy appears to be a relatively safe treatment for patients with recurrent glioblastoma, with only 9.5% of patients experiencing mild cytokine release syndrome and 25.4% having non-critical neurological events.

However, the therapy shows marginal efficacy, with a pooled objective response rate of only 5.1% and a median overall survival of 8.1 months, indicating that more research is needed to improve its effectiveness in treating this type of brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis. Jang, JK., Pyo, J., Suh, CH., et al.[2023]

CAR T-cell therapy shows potential for treating glioblastoma, a type of brain cancer, despite challenges such as identifying suitable antigens and overcoming an immunosuppressive environment.

Ongoing clinical trials and preclinical studies suggest that CAR T-cell therapy may evolve and be combined with existing treatments for better outcomes in glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy for glioblastoma. Rodriguez, A., Brown, C., Badie, B.[2021]

B7-H3 is highly overexpressed in glioblastoma (GBM) compared to normal brain tissue, making it a promising target for CAR-T cell therapy, as shown by immunohistochemistry in 76% of analyzed specimens.

B7-H3-redirected CAR-T cells effectively targeted and controlled tumor growth in GBM cell lines and patient-derived neurospheres in both in vitro and in vivo models, indicating their potential as a new treatment strategy for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres. Nehama, D., Di Ianni, N., Musio, S., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05366179

NCT05366179 | Autologous CAR-T Cells Targeting B7-H3 ... The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2062

Safety and efficacy of B7-H3 targeting CAR-T cell therapy ... The recurrent GBM (rGBM) exhibits a median survival of less than 8 months with limited therapeutic options. We have previously cloned the B7-H3 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6713854/

B7-H3 as a Novel CAR-T Therapeutic Target for ... Here, we aimed to explore whether B7-H3 could serve as a novel therapeutic target for GBM in chimeric antigen receptor (CAR) T cell therapy.

4. nature.com nature.com/articles/s41698-024-00753-0

CAR-T cell therapy for the treatment of adult high-grade ... Several CARs have been designed to target B7-H3 and these have shown promising results in preclinical studies. B7-H3 CAR-T cells are currently ...

5. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii158/7890491

IMMU-29. B7-H3-TARGETED CAR-T AND CAR-NK CELLS ... The results demonstrated that both B7-H3 CAR T cells and CAR NK cells exhibited significant cytotoxicity against patient-derived GBM cells in ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05366179/autologous-car-t-cells-targeting-b7-h3-in-recurrent-or-refractory-gbm-carb7-h3tc

Autologous CAR-T Cells Targeting B7-H3 in Recurrent ... The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.