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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with recurrent or worsening Grade 4 glioma, an aggressive brain cancer. The treatment, anti-B7-H3 CAR-T cell therapy, uses modified immune cells to target and fight cancer cells. Researchers focus on assessing the safety and tolerability of this treatment and determining the appropriate dosage for future studies. Suitable candidates for this trial include those who have undergone surgery and standard treatments for Grade 4 glioma but have experienced cancer recurrence or progression. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anti-B7-H3 CAR-T cell therapy, such as TX103, appears promising in early studies for treating brain cancer. These studies suggest that delivering the treatment directly into the brain's fluid spaces or a cavity within the brain is feasible and can be repeated.

Early results from a previous study indicated that this CAR-T cell therapy can be administered safely. Although specific side effects are not detailed, the studies have not identified major safety issues, suggesting the treatment is generally well-tolerated. However, it is important to remember that this is still early research.

Since this treatment is in a phase 1 trial, researchers are primarily assessing its safety and tolerability. At this stage, the treatment has not been widely tested, so unknown risks may still exist. Participants should discuss potential risks and benefits with their healthcare providers before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Most treatments for brain cancer, like chemotherapy and radiation, work by attacking rapidly dividing cells, but they can harm healthy cells too. Anti-B7-H3 CAR-T Cell Therapy is different because it uses genetically engineered T-cells to target and destroy cancer cells specifically, minimizing damage to healthy cells. Researchers are excited because this therapy can be delivered directly to the brain via intraventricular or intracavitary routes, potentially increasing its effectiveness against hard-to-treat brain tumors. Plus, its multi-dose approach allows for repeated targeting of the cancer, which could lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that anti-B7-H3 CAR-T cell therapy holds promise in fighting tumors. Studies have found that these CAR-T cells can effectively target and attack cancer cells, particularly in gliomas, a type of brain cancer. In this trial, participants will receive the therapy through different delivery methods. The Safety Run-In arm involves a single-dose administration of TX103 via intraventricular (ICV) or intracavitary (ICT) routes. Cohort A will receive multi-dose administration via a single delivery route (ICV), while Cohort B will receive multi-dose administration via dual delivery routes (ICT and ICV). Early tests demonstrated that injecting these CAR-T cells directly into the brain significantly reduced tumor size. Although this treatment is still under study, early signs suggest it could be a promising option for treating aggressive brain cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Gangxiong Huang, MD

Principal Investigator

Tcelltech Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10000604/

CAR T Cell Therapy in Glioblastoma - PubMed Central - NIH Combining CD70 and B7-H3 in tandem showed preclinical evidence of improved anti-tumor response in multiple cancers, including glioma [94].

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06482905

NCT06482905 | Safety and Efficacy Study of TX103 CAR-T ... 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 ...

3. trials.braintumor.org trials.braintumor.org/trials/NCT06482905

Safety and Efficacy Study of TX103 CAR-T Cell Therapy for ... 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 ...

4. journals.lww.com journals.lww.com/hosct/fulltext/2025/04000/a_critical_review_of_car_t_therapies_for.1.aspx

A Critical Review of CAR-T Therapies for Glioblastoma For more than 20 years, CAR-T cell therapy has been used with some success in glioblastoma patients, and interest in this field of study is steadily growing.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625001789

Review CAR T cell therapy for glioblastoma CAR T cells have been safely administered through both peripheral and locoregional routes but with variable clinical and radiographic efficacy.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/507955

Safety and Efficacy Study of TX103 CAR-T Cell Therapy for ... 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 ...