CAR-T Cell Therapy for Glioblastoma

Overseen by Yasmeen Rauf

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

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 patients with glioblastoma. CAR.B7-H3T cells treatment has not been tested in humans and is not an approved treatment by the Food and Drug Administration for glioblastoma.

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.

What data supports the effectiveness of the treatment CAR.B7-H3T cells for glioblastoma?

Research shows that CAR-T cells targeting B7-H3, a protein found in high levels in glioblastoma, have demonstrated antitumor effects in lab and animal studies, leading to longer survival in treated groups compared to controls. ^{1 2 3 4 5}

Is CAR-T cell therapy targeting B7-H3 safe for humans?

Recent studies suggest that CAR-T cell therapy, including those targeting B7-H3, is generally safe for humans, with clinical trials showing feasibility and safety in treating glioblastoma, although more research is needed to fully understand its safety profile. ^{1 4 5 6 7}

What makes CAR.B7-H3T cell therapy unique for treating glioblastoma?

CAR.B7-H3T cell therapy is unique because it targets the B7-H3 protein, which is often overexpressed in glioblastoma tumors, making it a promising new target for treatment. This approach uses genetically modified T cells to specifically attack cancer cells, offering a novel strategy compared to traditional treatments that may not specifically target tumor cells. ^{1 4 5 8 9}

Research Team

Yasmeen Rauf

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

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).

Trial Timeline

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

Treatment Details

Interventions

• CAR.B7-H3T cells (CAR T-cell Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

PD1 Expression in EGFRvIII-Directed CAR T Cell Infusion Product for Glioblastoma Is Associated with Clinical Response. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Potential of Glioblastoma-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy for glioblastoma. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells for Glioblastoma: Current Concepts, Challenges, and Future Perspectives. [2021]