CAR-T Cell Therapy for Brain Cancer

Recruiting at 3 trial locations

Overseen By Xianzhen Chen, MM

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tcelltech Inc.

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks per cycle

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I, open-Label, single/multiple dose, dose-escalation study to evaluate the safety, tolerability and antitumor activity of anti-B7-H3 CAR-T cell injection (TX103) in subjects with recurrent or progressive Grade 4 Glioma.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive agents or need long-term immunosuppressive therapy, you may not be eligible to participate.

What data supports the effectiveness of the treatment Anti-B7-H3 CAR-T Cell Therapy for brain cancer?

Research shows that targeting B7-H3 with CAR-T cells has shown promising results in preclinical studies for glioblastoma, a type of brain cancer, by extending survival in animal models. Additionally, B7-H3 is overexpressed in many solid tumors, making it a promising target for CAR-T cell therapy in brain cancers. ^{1 2 3 4 5}

What safety data exists for CAR-T Cell Therapy, including Anti-B7-H3 CAR-T, in humans?

CAR-T cell therapy, including Anti-B7-H3 CAR-T, has shown potential in treating various cancers, but it can cause significant side effects like cytokine release syndrome (CRS) and neurological toxicities. These side effects have been observed in clinical trials for different conditions, and while medical management has improved, the risk of unpredictable toxicities remains, especially in solid tumors. ^{1 3 4 6 7}

How is Anti-B7-H3 CAR-T Cell Therapy different from other treatments for brain cancer?

Anti-B7-H3 CAR-T Cell Therapy is unique because it targets the B7-H3 protein, which is often found in high levels on brain cancer cells like glioblastoma, making it a promising target for treatment. This therapy uses modified immune cells (CAR-T cells) to specifically attack cancer cells, potentially offering a new option for patients with few effective treatments available. ^{1 3 4 5 8}

Research Team

Gangxiong Huang, MD

Principal Investigator

Tcelltech Inc.

Eligibility Criteria

This trial is for adults aged 18-75 with Grade 4 Glioma, such as glioblastoma, that has come back or gotten worse after standard treatment. They must have B7-H3 positive tumors and be in a condition where they can perform daily activities to some extent (KPS score ≥60). Their heart should pump well (LVEF ≥40%) and they need good oxygen levels while resting.

Inclusion Criteria

My oxygen levels are 95% or higher when resting.

I agree to participate in the study and follow its procedures.

I have a grade 4 brain tumor and it has gotten worse after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TX103 CAR-T cell therapy in a dose-escalation study with two infusions on Day 1 and Day 8, followed by a 14-day observation period in a 21-day treatment cycle

3 weeks per cycle

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose limiting toxicities and adverse events

6 months

Long-term Follow-up

Participants are monitored for long-term outcomes such as incidence of secondary malignancies and overall survival

up to 15 years

Treatment Details

Interventions

• Anti-B7-H3 CAR-T Cell Therapy

Trial Overview The study tests TX103 CAR-T cell therapy's safety and effectiveness against aggressive brain cancer. It's an early-stage trial to find the highest dose patients can take without serious side effects and decide on the best dose for future studies.

Participant Groups

Group I: Safety Run-In Experimental Treatment 1 Intervention

Single-dose administration of TX103 via intraventricular(ICV) or intracavitary (ICT) .

Group II: Cohort B Dual delivery route(Multi-dose) Experimental Treatment 1 Intervention

Administration of TX103 on Day 1 via intracavitary (ICT) and on Day 8 via intraventricular(ICV) in a 21-day treatment cycle.

Group III: Cohort A Single delivery route(Multi-dose) Experimental Treatment 1 Intervention

Administration of TX103 via intraventricular(ICV) on Days 1 and 8 in a 21-day treatment cycle.

Who Is Running the Clinical Trial?

Tcelltech Inc.

Lead Sponsor

Trials

1

Recruited

50+

Beijing Tiantan Hospital

Collaborator

Trials

464

Recruited

11,100,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Findings from Research

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]

B7-H3 is a promising target for immunotherapy in solid tumors due to its overexpression in tumors and limited presence in normal tissues, making it a suitable candidate for chimeric antigen receptor (CAR) therapies.

Initial trials of B7-H3-targeted CAR-T cell therapies have shown safety, but their effectiveness has been limited; strategies such as local delivery, enhancing CAR-T cell persistence, and combining with other treatments may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3-targeted CAR-T cell therapy for solid tumors. Li, G., Wang, H., Wu, H., et al.[2022]

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 CAR T cells have shown significant antitumor activity in various pediatric solid tumor models, including osteosarcoma and medulloblastoma, indicating their potential as a treatment option for relapsed pediatric malignancies.

The effectiveness of B7-H3 CAR T cells is linked to the density of the B7-H3 antigen on tumor cells, suggesting that this therapy could be selectively effective against tumors with high antigen expression while minimizing effects on normal tissues with lower expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Majzner, RG., Theruvath, JL., Nellan, A., et al.[2021]

B7-H3 is a promising target for immunotherapy in treating various brain cancers, as it helps create a tumor-friendly environment that allows cancer cells to grow and resist treatment.

Preclinical studies and early-phase trials have shown that targeting B7-H3 can lead to effective anti-tumor responses with manageable toxicity, and ongoing clinical trials are exploring its use in combination therapies for difficult-to-treat brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 in Brain Malignancies: Immunology and Immunotherapy. Guo, X., Chang, M., Wang, Y., et al.[2023]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

The first three patients with diffuse intrinsic pontine glioma (DIPG) treated with B7-H3-specific CAR T cells showed no dose-limiting toxicities after receiving 40 infusions, indicating the treatment's safety and tolerability.

One patient experienced sustained clinical and radiographic improvement for 12 months, suggesting potential efficacy, while the presence of CAR T cells in cerebrospinal fluid (CSF) and local immune activation were observed, supporting the treatment's mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety. Vitanza, NA., Wilson, AL., Huang, W., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

B7-H3-targeted CAR-T cell therapy for solid tumors. [2022]

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

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

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

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. [2021]

5. Australia pubmed.ncbi.nlm.nih.gov

B7-H3 in Brain Malignancies: Immunology and Immunotherapy. [2023]

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

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]

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

Building safety into CAR-T therapy. [2023]

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

Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety. [2023]