Gamma-Delta T Cell Therapy for Glioblastoma

(DRI Trial)

Overseen By Thiru Pillay, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must be taking: Temozolomide

Must not be taking: Aminobisphosphonates

Disqualifiers: Encephalitis, Multiple sclerosis, HIV, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental cell therapy, known as DRI cell therapy, to determine its safety and tolerability in people with newly diagnosed glioblastoma multiforme (GBM), an aggressive brain cancer. Participants will receive this new treatment alongside standard chemotherapy. Ideal candidates have an MRI indicating a malignant brain tumor and have completed initial chemotherapy and radiation treatment. 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.

Do I need to stop taking 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 any other investigational agents or have received certain treatments like cellular immunotherapy or gene therapy within 6 weeks before the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that DRI cell therapy for glioblastoma is generally safe. Studies found that patients who received this therapy did not experience serious side effects or reactions that would limit the dose. Importantly, no instances of cytokine release syndrome, a serious immune reaction, occurred.

In one study, patients who received DRI cell therapy along with standard treatment demonstrated good safety results. The therapy was well-tolerated, and no major safety issues were reported. These findings are encouraging for those considering participation in a clinical trial for DRI cell therapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for glioblastoma, which typically involves radiation and chemotherapy with temozolomide, the DRI cell therapy uses modified gamma-delta T cells to target the cancer. These gamma-delta T cells are a type of immune cell capable of recognizing and attacking tumor cells directly. Researchers are excited about this approach because it harnesses the body's immune system to potentially improve precision and effectiveness in attacking cancer cells without harming healthy tissue. This innovative method represents a promising shift from traditional treatments that often come with significant side effects.

What evidence suggests that this treatment might be an effective treatment for glioblastoma?

Research has shown that gamma-delta T cell therapy, specifically DRI cell therapy, may help treat glioblastoma, an aggressive brain tumor. One study found that 11 out of 13 patients maintained stable disease after receiving this treatment. In another case, a patient with a similar brain tumor remained in remission, with no tumor regrowth, for four years following therapy. These findings suggest that DRI cell therapy might control tumor growth and extend the lives of patients with aggressive brain tumors like glioblastoma. Although still in early stages, these results offer hope for the treatment's effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Louis B Nabors, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed glioblastoma multiforme (GBM) who've finished standard treatment and are set for maintenance therapy. They need good organ/marrow function, a Karnofsky Performance Status ≥70%, and an MRI suggesting malignant glioma. Excluded are those with HIV, prior transplants, other GBM treatments, unstable health conditions, or women who are pregnant/breastfeeding.

Inclusion Criteria

My organ and bone marrow functions are within normal ranges.

My MRI suggests I might have a serious brain tumor.

I've finished initial treatment for brain cancer and am ready for ongoing therapy.

Exclusion Criteria

I do not have any severe illnesses or mental health issues that would prevent me from following the study's requirements.

I needed more steroids recently before getting a specific cell therapy.

I have had encephalitis, multiple sclerosis, or another brain infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure

Subjects undergo surgical resection to remove the tumor and have a Rickham catheter placed

1 week

1 visit (in-person)

Apheresis and Cell Synthesis

Apheresis procedure to collect PBMCs for DRI γδ T cell synthesis

1 week

1 visit (in-person)

Initial Treatment

6 weeks of chemotherapy with TMZ and radiation

6 weeks

Maintenance Treatment

6 cycles of TMZ with DRI γδ T cell injections through the Rickham catheter

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term Follow-up

Monitoring for disease progression and overall survival

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• DRI cell therapy

Trial Overview The trial is testing the safety of DRI γδ T cell therapy combined with temozolomide in patients with new GBM. It's experimental and involves two parts: initial surgery to place a device for drug delivery and then receiving the actual cell therapy.

How Is the Trial Designed?

Group I: DRI cell therapy Experimental Treatment 1 Intervention

The only arm will receive the DRI modified gamma delta T cells following standard therapy with radiation and temozolomide chemotherapy concurrent.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

In8bio Inc.

Industry Sponsor

Trials

3

Recruited

60+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04165941

NCT04165941 | Novel Gamma-Delta (γδ)T Cell Therapy ... This study is being conducted to find out if the safety and tolerability of an experimental cell therapy is safe to administer to patients with a newly ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2007

INB-200: Phase 1 study of gene-modified autologous ... 2007. Background: Recent cell therapy and CAR-T initiatives for GBM have shown initial responses but durability has been disappointing.

3. investors.in8bio.com investors.in8bio.com/news-releases/news-release-details/in8bio-recognizes-achievement-4-years-remission-patient-treated

IN8bio Recognizes Achievement of 4-Years in Remission for ... The patient, with a grade 4, IDH-mutant glioma, has been in remission and surviving for 4 years having been treated with INB-200.

4. onclive.com onclive.com/view/clinical-development-of-gamma-delta-t-cell-therapy-inb-400-paused-in-glioblastoma

Clinical Development of Gamma-Delta T-Cell Therapy INB ... Among the 13 patients who received treatment, 1 had a best response of progressive disease (PD), 11 had best responses of stable disease, and 1 ...

5. onealcanceruab.org onealcanceruab.org/news-and-events/news/encouraging-phase-1-data-for-glioblastoma-treatment-reported-by-uab-researchers-at-asco/

Encouraging Phase 1 data for glioblastoma treatment ... This Stupp regimen achieves a median progression-free survival of seven months and an overall survival of approximately 14 to 16 months. The Phase 1 study ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9245381/

Gamma Delta T-Cell Based Cancer Immunotherapy Preliminary results show a good safety profile with activation of Vγ9Vδ2 T-cells and increased tumor infiltration in one melanoma patient. Stable disease has ...