Gene-Modified T Cell Therapy for Glioblastoma

Recruiting at 7 trial locations

Overseen By Stacey Bilinski

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: In8bio Inc.

Must be taking: Temozolomide

Must not be taking: Investigational agents, Immunotherapy

Disqualifiers: Concurrent malignancy, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 3

4 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have received certain therapies recently, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment using genetically modified gamma-delta T cells for glioblastoma?

Research shows that gamma-delta T cells can recognize and attack glioblastoma cells, and genetically modified versions of these cells have been shown to kill glioblastoma cells in lab studies and animal models. Additionally, these cells can work alongside chemotherapy to target resistant cancer cells, suggesting a potential benefit in treating glioblastoma. ^{1 2 3 4 5}

Is gene-modified T cell therapy safe for humans?

Research suggests that gamma-delta T cell therapy is generally safe for brain tumor patients, even those who have undergone standard treatments like radiation and chemotherapy, as it does not harm normal brain tissue. ^{2 3 5 6 7}

How is the gene-modified T cell treatment for glioblastoma different from other treatments?

This treatment uses genetically modified gamma-delta T cells, which are a unique type of immune cell that can recognize and attack glioblastoma cells without needing the usual antigen processing. Unlike traditional treatments, these T cells can be allogeneic (from a donor) or autologous (from the patient), offering a novel approach to target the tumor's immune-evasive properties. ^{1 2 4 7 8}

What is the purpose of this trial?

This multicenter, Phase 1b/2 study is being conducted to determine if the experimental cell therapy is safe, tolerable and can delay the return of cancer in patients with a newly diagnosed or recurrent glioblastoma multiforme (GBM) in combination with standard chemotherapy treatment temozolomide (TMZ). If there is a 25% or greater improvement in survival in this study then the therapy should be studied further.

Research Team

Louis B Nabors, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults with newly diagnosed or recurrent glioblastoma who haven't had more than one standard therapy and no prior Avastin, unless for edema. They must be in good physical condition (Karnofsky Performance ≥ 70%), agree to use two birth control methods if of childbearing potential, and have a suitable donor for the cell therapy. Exclusions include recent vaccinations or surgery, unresolved treatment side effects, other cancers within two years (unless low risk), allergies to certain drugs, uncontrolled illnesses that affect study compliance or interpretation.

Inclusion Criteria

I am willing to have a Rickham catheter placed and kept in.

Subjects in Phase 1b and Arm B and Arm C must have a partially matched haploidentical or matched related donor

My MRI suggests I might have a recurring brain tumor.

Exclusion Criteria

I haven't had encephalitis, multiple sclerosis, or a CNS infection in the year before my brain cancer diagnosis.

I received a vaccine or had surgery within the specified times before my leukapheresis collection.

I haven't had certain cancer treatments like immunotherapy or surgery in the weeks before joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgical Resection and Apheresis

Participants undergo surgical resection of the tumor and apheresis to collect immune cells for DRI product preparation

4 weeks

2 visits (in-person)

Initial Treatment

Participants receive six weeks of chemotherapy with TMZ and radiation, followed by a four-week break

10 weeks

Weekly visits (in-person)

Maintenance Treatment

Participants receive maintenance therapy with TMZ and DRI product infusions every 28 days for six cycles

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Quarterly visits (in-person)

Treatment Details

Interventions

• Allogeneic genetically modified gamma-delta T cells
• Autologous genetically modified gamma-delta T cells

Trial Overview The trial tests genetically modified gamma-delta T cells from either the patient (autologous) or a donor (allogeneic) combined with temozolomide chemotherapy in patients with glioblastoma. The goal is to see if this experimental cell therapy can improve survival by at least 25% compared to current treatments.

Participant Groups

Group I: 3) Allogeneic Newly Diagnosed Disease: Phase 2 Arm C Experimental Treatment 0 Interventions

Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Group II: 2) Allogeneic Relapsed Disease: Phase 1b and Phase 2 Experimental Treatment 1 Intervention

Phase 1b subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Group III: 1) Autologous Newly Diagnosed Disease: Phase 2 Arm A Experimental Treatment 0 Interventions

Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Who Is Running the Clinical Trial?

In8bio Inc.

Lead Sponsor

Trials

3

Recruited

60+

References

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

Gammadelta T cells as immune effectors against high-grade gliomas. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Human gamma-delta (γδ) T cell therapy for glioblastoma: A novel alternative to overcome challenges of adoptive immune cell therapy. [2023]

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

Human allogenic γδ T cells kill patient-derived glioblastoma cells expressing high levels of DNAM-1 ligands. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Genetically modified T cells to target glioblastoma. [2021]

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

Engineered drug resistant γδ T cells kill glioblastoma cell lines during a chemotherapy challenge: a strategy for combining chemo- and immunotherapy. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

The safety of allogeneic innate lymphocyte therapy for glioma patients with prior cranial irradiation. [2021]

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

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma. [2021]