CAR T-Cell Therapy for Glioblastoma

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

42 Participants Needed

Trial Summary

What is the purpose of this trial?

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, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).

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.

What data supports the effectiveness of the treatment CHM-1101 CAR-T cells for glioblastoma?

Research on similar CAR T-cell therapies for glioblastoma shows some promise, with objective responses reported in trials targeting different proteins on tumor cells. These studies suggest that CAR T-cell therapy can potentially engage the immune system to fight glioblastoma, although challenges remain in achieving consistent results. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy has shown feasibility and safety in glioblastoma patients, with some studies indicating it is a safe alternative to traditional methods. However, there are risks of severe side effects like cytokine release syndrome (a severe immune reaction) and neurological toxicities, especially in certain conditions like acute lymphocytic leukemia. ^{1 6 7 8 9}

What makes CHM-1101 CAR-T cell therapy unique for treating glioblastoma?

CHM-1101 CAR-T cell therapy is unique because it uses genetically modified T cells to target multiple forms of the EGFR protein, which is often altered in glioblastoma tumors. This approach aims to reduce tumor escape by addressing tumor heterogeneity, a common challenge in treating glioblastoma. ^{1 3 5 7 10}

Research Team

Jason Litten, MD

Principal Investigator

Chimeric Therapeutics

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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 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 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, 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 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]

References

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

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

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

CAR T-Cell Therapies in Glioblastoma: A First Look. [2019]

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

Optimizing CAR-T Therapy for Glioblastoma. [2023]

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

Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

8. 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]

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

Multifunctional mRNA-Based CAR T Cells Display Promising Antitumor Activity Against Glioblastoma. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

High-Affinity Chimeric Antigen Receptor With Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms. [2021]