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

Randomized Phase 2b Study of Safety And Efficacy Of TVI-Brain-1 Combined With Conformal Radiotherapy And Temozolomide Vs Standard Therapy In Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma Multiforme of Brain
• Intervention / Treatment: Procedure: Standard of Care; Radiation: Radiotherapy; Drug: Temozolomide; Biological: TVI-Brain-1

Detailed Description

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 general procedures include the collection and testing of cancer tissue samples after surgery and chemoradiation therapy (radiation and temozolomide). For the patients randomized into the investigational study treatment group, they will also receive two vaccinations created from their own cancer cells, undergo leukapheresis to collect immune T-cells from their blood, and transfer of those activated effector T-cells after chemoradiation therapy. All patients are followed with MRIs at follow-up visits.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Center for Neurosciences
  • California
    • Los Angeles, California, United States, 90048
      • Cedar-Sanai Medical Center
    • Los Angeles, California, United States, 90048
      • University of Southern California Keck School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Aaron Mammoser
  • Kansas
    • Kansas City, Kansas, United States, 66061
      • University of Kansas Medical Center
  • New Jersey
    • Pennington, New Jersey, United States, 08534
      • Capital Health
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; 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; Surgery for tumor removal or debulking to minimize tumor burden; Radiation: Radiotherapy; 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.; Drug: Temozolomide; 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 .; Other Names: Chemotherapy
Experimental: Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells; 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.	Procedure: Standard of Care; Surgery for tumor removal or debulking to minimize tumor burden; Radiation: Radiotherapy; 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.; Drug: Temozolomide; 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 .; Other Names: Chemotherapy; Biological: TVI-Brain-1; Attenuated autologous cancer cells and activated autologous blood-derived t cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Time to progression is evaluated by review and analysis of serial MRI's taken at specific Time to progression is evaluated by review and analysis of serial MRI's taken at specific timepoints	From date of randomization until the date of first documented progression assessed up to 24 months after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Assessment of changes in patient through Physical Examination	Through study completion, an average of 2 years
Immunogenicity	Delayed-type hypersensitivity (DTH) skin testing using attenuated autologous cancer cells will be performed to assess the immunogenicity of the Subject's cancer.	Assessed at 24 hours after each vaccine administration
Other genetic and immunologic parameters	The study is also designed to determine whether a wide variety of genetic and immunologic parameters that are monitored during and following treatment correlate with clinical outcomes	Assessed at 24 hours after each vaccine administration

Collaborators and Investigators

• Sponsor: TVAX Biomedical
• Collaborators: FDA Office of Orphan Products Development
• Investigators: Study Director: Jean Aguiar, APRN, TVAX Biomedical, Inc

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 22, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 13, 2023

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: TVI-AST-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No