Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)

NCT05685004 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TVI-AST-008
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 8

Brief Summary

This randomized study is designed to compare the combination of TVI-Brain-1 immunotherapy and standard therapy compared to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. The patients' own cancer cells collected after surgery are combined into a vaccine to produce an immune response that significantly increases the number of cancer neoantigen-specific effector T cell precursors in the patient's body. These cancer neoantigen-specific T cells are harvested from the blood, subsequently stimulated and expanded, and infused back into the patient.

Conditions

Glioblastoma Multiforme of Brain

Outcome Measures

Primary Outcomes (1)

• Survival

  All Subjects will be evaluated and contacted to evaluate their status

  From date of randomization until the date of death from any cause assessed up to 24 months after randomization.

Secondary Outcomes (1)

• Progression-free survival

  From date of randomization until the date of first documented progression assessed up to 24 months after randomization

Other Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Through study completion, an average of 2 years

• Immunogenicity

  Assessed at 24 hours after each vaccine administration

• Other genetic and immunologic parameters

  Assessed at 24 hours after each vaccine administration

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Subjects will have standard surgery which will be followed approximately 5 weeks later by combined radiotherapy and chemotherapy consisting of temozolomide 75 mg/m2 dosed once daily beginning on the first day of radiotherapy and continuing until the final day of radiotherapy. Subjects will receive adjuvant temozolomide, and proceed with post therapy surveillance.

Procedure: Standard of Care; Radiation: Radiotherapy; Drug: Temozolomide

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells

EXPERIMENTAL

TVI-Brain-1 immunotherapy is integrated with radiation and temozolomide in the test group in the following manner: 1) Subjects undergo surgical resection of their cancer and are tapered off steroids. 2) Subjects receive the first vaccination of TVI-Brain-1 as soon as the laboratory prepared vaccine is available for use (approximately 7 - 14 days following surgery). 3) Subjects receive a second vaccination 7-10 days later. 4) Subjects are leukapheresed to obtain immune T cells for ex vivo-activation. 5) Subjects' T cells are stored frozen until after chemoradiotherapy is completed. 6) Following chemoradiotherapy Subjects are infused with activated effector T cells followed by a 10-day course of low-dose interleukin 2 (IL-2). 7) Subjects then proceed with post therapy surveillance.

Biological: TVI-Brain-1; Procedure: Standard of Care; Radiation: Radiotherapy; Drug: Temozolomide

Interventions

TVI-Brain-1 BIOLOGICAL

Attenuated autologous cancer cells and activated autologous blood-derived t cells

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells

Standard of Care PROCEDURE

Surgery for tumor removal or debulking to minimize tumor burden

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells; Standard of Care

Radiotherapy RADIATION

Conformal radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday through Friday) over a period of six weeks.

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells; Standard of Care

Temozolomide DRUG

All Subjects receive 75 mg/m2 of temozolomide daily beginning on the first day of radiotherapy and continuing until the completion of radiotherapy. Standard of care Subjects will also receive adjuvant temozolomide .

Also known as: Chemotherapy

Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells; Standard of Care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed MGMT unmethylated glioblastoma multiforme (no prior treatment)
• Sufficient cancer tissue obtained to allow for manufacture of autologous cancer cell vaccines
• The attenuated autologous cancer cell product generated has satisfied the product release criteria as determined by the sponsor quality control department
• Medical history, physical examination and laboratory testing performed within approximately 7 days before enrollment revealing kidney and liver organ function within normal limits
• not currently receiving glucocorticoids and have been off glucocorticoids for at least 24 hours prior to vaccination as well as when they receive the T cell infusion.
• Patient function assessment (Karnofsky score is \> 60)
• a life expectancy of \> 12 weeks.
• Hemoglobin is \> 10 g/dL (may be transfused)
• White blood cell count is \> 3,000 cells/microliter (mcL) of blood.
• Platelet count is \> 100,000 platelets per mcL of blood (transfusion independent)
• Lymphocyte count is \> 1,000 cells/mcL of blood.

You may not qualify if:

• another concomitant life-threatening disease (not including glioblastoma multiforme)
• a second malignancy that is not in remission as determined by the clinical investigator. Exception: squamous or basal cell carcinoma of the skin.
• requirement for treatment with glucocorticoids to control brain swelling
• presence of active autoimmune disease that is currently being actively treated.
• psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol.
• Current pregnancy or a plan to become pregnant within 1-year following the study.

Sponsors & Collaborators

• TVAX Biomedical: lead

Study Sites (8)

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

Cedar-Sanai Medical Center

Los Angeles, California, 90048, United States

Location

University of Southern California Keck School of Medicine

Los Angeles, California, 90048, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Aaron Mammoser

Atlanta, Georgia, 30309, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66061, United States

Location

Capital Health

Pennington, New Jersey, 08534, United States

Location

Providence St. Vincent

Portland, Oregon, 97225, United States

Location

Related Publications (5)

• Holladay FP, Heitz T, Chen YL, Chiga M, Wood GW. Successful treatment of a malignant rat glioma with cytotoxic T lymphocytes. Neurosurgery. 1992 Sep;31(3):528-33. doi: 10.1227/00006123-199209000-00015.

  PMID: 1407433 BACKGROUND

• Holladay FP, Heitz T, Wood GW. Antitumor activity against established intracerebral gliomas exhibited by cytotoxic T lymphocytes, but not by lymphokine-activated killer cells. J Neurosurg. 1992 Nov;77(5):757-62. doi: 10.3171/jns.1992.77.5.0757.

  PMID: 1403119 BACKGROUND

• Plautz GE, Touhalisky JE, Shu S. Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells. Cell Immunol. 1997 Jun 15;178(2):101-7. doi: 10.1006/cimm.1997.1140.

  PMID: 9225000 BACKGROUND

• Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000 Dec 15;9(6):e9. doi: 10.3171/foc.2000.9.6.10.

  PMID: 16817692 BACKGROUND

• Wood GW, Turner T, Wang YY, Holladay FP. Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats. J Immunother. 1999 Nov;22(6):497-505. doi: 10.1097/00002371-199911000-00004.

  PMID: 10570748 BACKGROUND

MeSH Terms

Interventions

Standard of Care; Radiotherapy; Temozolomide; Drug Therapy

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jean Aguiar, APRN

  TVAX Biomedical, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded over-read of sequential MRI assessments
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2022
• First Posted: January 13, 2023
• Study Start: September 15, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)