Gene-Modified T Cell Therapy for Glioblastoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy for glioblastoma (a type of brain cancer) to determine if it can safely delay the cancer's return. The study combines genetically modified T cells (a type of immune cell therapy) with a standard chemotherapy drug called temozolomide. Different groups within the trial focus on those with newly diagnosed or relapsed glioblastoma. The trial seeks participants with glioblastoma who have not received extensive prior treatments and can identify a suitable donor if required. As a Phase 1 trial, the 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 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.

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

Research has shown that using a person's own genetically modified T cells has been tested for safety in earlier studies. These studies found that the side effects of these T cells are manageable, meaning they are not too severe and can be controlled. Evidence suggests these T cells might help slow the progression of the disease.

For T cells from donors, another study tested their safety in humans for the first time. This research found that these cells could effectively target and destroy brain tumor cells called glioblastoma. The study mainly focused on ensuring the treatment is safe and can be given to patients without causing serious side effects.

Overall, both types of T cells have shown promising safety results in early studies. Ongoing research is important to confirm these findings and to determine their effectiveness when combined with chemotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard options for glioblastoma, which often include surgery, radiation, and chemotherapy like temozolomide, this new treatment uses genetically modified gamma-delta T cells. These cells are engineered to target and attack cancer cells more precisely. Researchers are excited because these T cells can be derived from the patient's own cells (autologous) or from a donor (allogeneic), potentially offering flexibility and effectiveness in treating both newly diagnosed and relapsed cases. This approach could enhance the immune system's ability to fight the tumor, offering a more targeted and potentially less toxic treatment than traditional chemotherapy.

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

Research has shown that gamma-delta T cells, a type of immune cell, might help fight glioblastoma, a type of brain cancer. In this trial, some participants will receive autologous genetically modified gamma-delta T cells, derived from the patient's own cells. Studies have found that using a patient's own gamma-delta T cells can be safe and show positive results in treating glioblastoma. This approach aims to strengthen the body's immune system to attack the cancer.

Other participants will receive allogeneic genetically modified gamma-delta T cells, derived from a donor. Early lab tests showed that these donor-derived cells can reduce tumor size and improve survival in mice with glioblastoma. These cells work by finding and destroying cancer cells, offering a potential new treatment for this aggressive cancer. Overall, early evidence is promising for both methods, but more research is needed to confirm their effectiveness in humans. ^{2 3 4 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?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9629076/

Human allogenic γδ T cells kill patient-derived glioblastoma ... Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand–receptor

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05664243

Study Details | NCT05664243 | A Phase 1b / 2 Drug ... This is a Phase 1b and 2 open-label cellular therapy trial using genetically modified gamma-delta (γδ) T cells or DeltEx Drug Resistant Immunotherapy (DRI).

3. mdpi.com mdpi.com/2072-6694/17/16/2660

γδ T Cells in Glioblastoma Multiforme: Novel Roles and ... In preclinical models, the adoptive transfer of γδ T cells has been shown to enhance survival and reduce tumor burden in GBM-bearing mice, further supporting ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383523002860

Human gamma-delta (γδ) T cell therapy for glioblastoma Our study introduced γδ T cells as an alternative and novel option to overcome several challenges regarding immune cell therapy in glioblastoma treatment.

5. investors.in8bio.com investors.in8bio.com/news-releases/news-release-details/in8bio-present-data-highlighting-potential-inb-200-and-inb-400

IN8bio to Present Data Highlighting Potential of INB-200 and ... GBM remains a disease with significant unmet need, with limited treatment options and poor associated outcomes.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07144735

NCT07144735 | Allogeneic γδT Cells in Glioblastoma This first-in-human clinical study aims to evaluate the safety and feasibility of locally delivered, allogeneic γδ T cells (genetically edited ...