CAR T-Cell Therapy for Glioblastoma

Not currently recruiting at 1 trial location

Overseen By Chimeric Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chimeric Therapeutics

Must not be taking: Bevacizumab

Disqualifiers: Uncontrolled seizures, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CHM-1101 CAR-T cells, a type of immunotherapy, to determine its safety and effectiveness for people with glioblastoma, a type of brain cancer that has returned or worsened. The trial aims to find the best dose and assess how well it targets and attacks cancer cells. Suitable participants have experienced glioblastoma recurrence after standard treatments and have a specific tumor marker called MMP2+. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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, it mentions that you should not have uncontrolled illnesses or active infections, which might imply some medication adjustments. Please consult with the trial team for specific guidance.

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

Research has shown that CHM-1101 CAR-T cell therapy is being tested for safety in treating glioblastoma, a type of brain cancer. In some early studies, patients demonstrated that this therapy can be administered safely, with few reports of serious side effects. For instance, one study found that delivering a similar CAR-T therapy directly into the brain was safe, and patients tolerated it well.

However, since this is an early-stage study, safety information is still being gathered. These trials aim to find the best dose and understand how the treatment affects patients. While the initial results are promising, potential participants should stay informed and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which often involve surgery, radiation, and chemotherapy, CHM-1101 CAR-T cell therapy offers a novel approach by using the body's own immune cells to fight the tumor. This treatment is unique because it involves genetically engineering T-cells to target cancer cells specifically. Researchers are excited about this therapy because it has the potential to provide a more targeted and personalized attack on glioblastoma, which could lead to better outcomes with fewer side effects compared to traditional methods. Additionally, the delivery of the treatment directly into the tumor cavity and the brain's lateral ventricle is designed to maximize its effectiveness right where it's needed most.

What evidence suggests that CHM-1101 CAR-T cells might be an effective treatment for glioblastoma?

Studies have shown that CAR T-cell therapy could be promising for glioblastoma, a type of brain cancer. Research indicates that patients with recurring glioblastoma who received CAR T-cell therapy lived an average of 5.5 to 11.1 months. In some cases, progression-free survival, the time patients lived without the disease worsening, was about 7.5 months. In this trial, participants will receive the specific CAR T-cell therapy, CHM-1101, which targets a protein called MMP2 found in glioblastoma, suggesting it could effectively attack the cancer cells. These early findings suggest potential benefits in treating challenging cases of glioblastoma. ^{2 5 6 7 8}

Who Is on the Research Team?

Jason Litten, MD

Principal Investigator

Chimeric Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed grade 4 glioblastoma or malignant glioma that's worsened to grade 4, and have MMP2+ tumors. They must be in relatively good health (ECOG status of 0 or 1), not pregnant, agree to birth control, HIV negative, and without significant other illnesses. Those who've had recent bevacizumab therapy or uncontrolled seizures can't join.

Inclusion Criteria

Agreement to allow the use of archival tissue from diagnostic tumor biopsies

Women of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required

Seronegative for hepatitis B and/or hepatitis C virus

Exclusion Criteria

I do not have any other active cancer.

I received bevacizumab therapy within the last 3 months.

I am still experiencing side effects from my previous cancer treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CHM-1101 CAR T cell therapy through dual delivery via intracavitary and intraventricular catheters. Cycle 1 lasts 28 days with 3 once-weekly administrations.

4 weeks

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment. Monitoring includes assessments of cytokine release syndrome and other adverse events.

12 months

Long-term Follow-up

Participants are monitored for overall survival, endogenous T cell levels, and human anti-CAR antibody presence.

up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CHM-1101 CAR-T cells

Trial Overview The study tests CHM-1101 CAR-T cells on patients with recurrent or worsening glioblastoma. It aims to find the safest dose and measure how effective these genetically engineered immune cells are at targeting tumor cells expressing a specific protein (MMP2).

How Is the Trial Designed?

Group I: Treatment (CAR T cell therapy) 2 Experimental Treatment 1 Intervention

Arm 2 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle. Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations. After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

Group II: Treatment (CAR T cell therapy) 1 Experimental Treatment 1 Intervention

Arm 1 participants will undergo resection of their tumor. Participants receive half the CHM-1101 dose via Rickham catheters into the tumor cavity and half into the lateral ventricle. Cycle 1 (28 days) CHM 1101 total dose will be divided across 3 once-weekly administrations. After Cycle 1, additional cycles may be initiated in the absence of disease progression or unacceptable toxicity provided that the principal investigator and participant agree to continue and if adequate autologous CAR-T doses remain.

Who Is Running the Clinical Trial?

Chimeric Therapeutics

Lead Sponsor

Trials

2

Recruited

180+

Published Research Related to This Trial

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]

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]

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, 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05627323

NCT05627323 | CAR T Cells in Patients With MMP2+ ... This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11241811/

CAR-T Cells Therapy in Glioblastoma: A Systematic Review ... Median OS ranged from 5.5 to 11.1 months across the studies. PFS was reported in only two studies, with values of 7.5 months and 1.3 months.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS2086

Phase 1b multicenter study to evaluate CHM 1101 in ... Patients with recurrent GBM have a poor prognosis, with limited treatment options and a median survival of less than 1 year (Gallego. Curr Oncol ...

4. journals.lww.com journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/09000/car_t_cell_therapy_for_glioblastoma__advances,.48.aspx

CAR-T cell therapy for glioblastoma: advances, challenges,... Chimeric antigen receptor T (CAR-T) therapy for glioblastoma involves critically evaluating progress, effectiveness, and challenges.

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

CAR-T cell therapy for the treatment of adult high-grade ... In this review, we provide an overview of the current landscape of clinical trials and the development of novel strategies aimed at optimizing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705370/

Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma This review explores the potential of chimeric antigen receptor (CAR) T-cell immunotherapy as a promising approach for treating GBM.

7. 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 There is a relatively small but enhancing body of clinical trials studying the effectiveness of CAR-T in treating glioblastoma, known as the most common and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666379125003751

Chlorotoxin-directed CAR T cell therapy for recurrent ... With the overall goal of evaluating safety and feasibility, we report here our interim observations from an initial patient cohort receiving ...