Glioblastoma Multiforme of BrainPhase 2/3NCT05685004
Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
A Phase 2/3 study testing TVI-Brain-1, Radiotherapy and Temozolomide in people with Glioblastoma Multiforme of Brain, run by TVAX Biomedical at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glioblastoma Multiforme of Brain
- What is being tested?
- TVI-Brain-1, Radiotherapy and Temozolomide
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 8 sitesUnited States
- Study dates
- 27 Dec 2023to Nov 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Piedmont
Atlanta, Georgia, 30309
University of Kansas Medical Center
Kansas City, Kansas, 66061
Cedar-Sanai Medical Center
Los Angeles, California, 90048
University of Southern California Keck School of Medicine
Los Angeles, California, 90048
Capital Health
Pennington, New Jersey, 08534
Providence St. Vincent
Portland, Oregon, 97225
Moffitt Cancer Center
Tampa, Florida, 33612
Center for Neurosciences
Tucson, Arizona, 85718
About this study
Official title: 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.
Read the 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.
- Conditions
- Glioblastoma Multiforme of Brain
- Being tested
- TVI-Brain-1, Standard of Care, Radiotherapy, Temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TVI-Brain-1Biological
Attenuated autologous cancer cells and activated autologous blood-derived t cells
Standard of CareProcedure or surgery
Surgery for tumor removal or debulking to minimize tumor burden
RadiotherapyRadiation
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.
TemozolomideDrug
Also called Chemotherapy
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 .
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: TVI-Brain-1; Procedure: Standard of Care; Radiation: Radiotherapy; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
All Subjects will be evaluated and contacted to evaluate their status
Measured: 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
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
Measured: From date of randomization until the date of first documented progression assessed up to 24 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2023
- Study start27 Dec 2023
- Primary completionNov 2030 (estimated)
- Study completionNov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma Multiforme of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TVAX Biomedical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gary Wood, PhD, Study chair, TVAX Biomedical, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05685004
- Sponsor's protocol ID
- TVI-AST-008
- Status last verified
- Sep 2026
- First submitted
- 22 Dec 2022
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 1407433Holladay 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.
PubMed 1403119Plautz 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.
PubMed 9225000Sloan 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.
PubMed 16817692Wood 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.
PubMed 10570748
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05685004
- Acronym / sponsor ID
- TVI-AST-008
- Conditions
- Glioblastoma Multiforme of Brain
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- TVAX BiomedicalIndustry (pharma, biotech, devices)
- Study start
- 27 Dec 2023 (actual)
- Primary completion
- Nov 2030 (estimated)
- Study completion
- Nov 2030 (estimated)
- First posted
- 13 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Procedure: Standard of Care, Radiation: Radiotherapy, Drug: TemozolomideSubjects 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. |
| Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells | Experimental | Biological: TVI-Brain-1, Procedure: Standard of Care, Radiation: Radiotherapy, Drug: TemozolomideTVI-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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TVI-Brain-1Attenuated autologous cancer cells and activated autologous blood-derived t cells | Biological | Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells |
| Standard of CareSurgery for tumor removal or debulking to minimize tumor burden | Procedure or surgery | Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells, Standard of Care |
| RadiotherapyConformal 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. | Radiation | Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells, Standard of Care |
| TemozolomideAlso: ChemotherapyAll 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 . | Drug | Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells, Standard of Care |
Primary outcome
Survival
Time frame: From date of randomization until the date of death from any cause assessed up to 24 months after randomization.
All Subjects will be evaluated and contacted to evaluate their status
1 secondary outcome
Progression-free survival
Time frame: From date of randomization until the date of first documented progression assessed up to 24 months after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Background: PubMed 1407433Holladay 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.
- Background: PubMed 1403119Holladay 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.
- Background: PubMed 9225000Plautz 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.
- Background: PubMed 16817692Sloan 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.
- Background: PubMed 10570748Wood 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Wood, PhD study chair
TVAX Biomedical, Inc
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing TVI-Brain-1, Radiotherapy and Temozolomide in people with Glioblastoma Multiforme of Brain, run by TVAX Biomedical at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: From date of randomization until the date of death from any cause assessed up to 24 months after randomization.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05685004, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.