Personalized Immunotherapy for Glioblastoma

Not currently recruiting at 9 trial locations

Overseen By Jean Aguiar

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: TVAX Biomedical

Must not be taking: Glucocorticoids

Disqualifiers: Second malignancy, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new personalized vaccine for individuals with glioblastoma, a specific type of brain cancer. It combines a novel immunotherapy treatment with standard cancer treatments, such as radiotherapy (also known as radiation therapy) and temozolomide, to determine if it is more effective than standard treatment alone. The vaccine uses a patient's own cancer cells to enhance the immune system's ability to fight the cancer. The trial seeks participants who have recently been diagnosed with glioblastoma and have not yet begun treatment. As a Phase 2, Phase 3 trial, it measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you are not currently taking glucocorticoids and have been off them for at least 24 hours before vaccination and T cell infusion. Other medications are not specified, so it's best to discuss with the trial team.

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

Research has shown that the TVI-Brain-1 immunotherapy underwent safety testing in earlier studies. These studies found that the treatment can extend the lives of patients with recurrent glioblastoma, indicating it is generally well-tolerated. Importantly, no major safety issues emerged, which is encouraging for its use.

Temozolomide, the other treatment in this trial, is already a common therapy for glioblastoma. Research indicates that it is safe and can extend patient survival when combined with radiation therapy. Patients have generally tolerated it well, even with long-term use.

Both treatments have evidence supporting their safety. TVI-Brain-1 has shown promise in earlier studies, and Temozolomide is a standard treatment with a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for glioblastoma, which typically involves surgery followed by radiotherapy and chemotherapy with temozolomide, the investigational treatment TVI-Brain-1 offers an innovative approach. This treatment is unique because it combines a personalized immunotherapy vaccine with the patient's own blood-derived T cells, which are activated outside the body before being reintroduced. This method aims to harness the body's immune system to target cancer more effectively. Researchers are excited about TVI-Brain-1 because its novel mechanism has the potential to enhance the immune response against glioblastoma, potentially improving outcomes for patients facing this aggressive brain cancer.

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

Research has shown that TVI-Brain-1 immunotherapy, one of the treatments studied in this trial, could effectively treat glioblastoma, a type of brain cancer. Studies have found that patients receiving TVAX Immunotherapy, which includes TVI-Brain-1, lived significantly longer on average compared to past data. Specifically, those with recurring glioblastoma had an average survival time of about 32 months. This treatment uses a vaccine made from the patient’s own cancer cells to help the immune system fight the tumor. It works by increasing the number of T cells, a type of immune cell, that specifically attack the cancer. Participants in this trial will receive either the TVI-Brain-1 immunotherapy or the standard of care, which includes surgery followed by radiotherapy and temozolomide. ^{1 2 4 5 6}

Who Is on the Research Team?

Jean Aguiar, APRN

Principal Investigator

TVAX Biomedical, Inc

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed MGMT unmethylated glioblastoma who haven't been treated before. They need enough tumor tissue from surgery to make a vaccine, normal kidney and liver function, no current steroid use, good physical function (Karnofsky score > 60), expected to live more than 12 weeks, and specific blood cell counts within the required range. Pregnant individuals or those planning pregnancy within a year are excluded.

Inclusion Criteria

My hemoglobin level is above 10 g/dL.

Lymphocyte count is > 1,000 cells/mcL of blood

I have a new diagnosis of a specific brain cancer (glioblastoma) without prior treatment.

Exclusion Criteria

Psychological, familial, sociological or geographical conditions that do not permit adequate medical follow-up and compliance with the study protocol

I have another cancer that is not in remission, except for skin cancer.

I need steroids to manage brain swelling.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment Preparation

Subjects undergo surgical resection of their cancer and are tapered off steroids. The first vaccination of TVI-Brain-1 is administered approximately 7-14 days following surgery.

2-3 weeks

Chemoradiotherapy

Subjects receive combined radiotherapy and chemotherapy with temozolomide, followed by leukapheresis to collect immune T cells.

5 weeks

Immunotherapy and T Cell Infusion

Subjects receive a second vaccination, undergo leukapheresis, and are infused with activated effector T cells followed by a 10-day course of low-dose interleukin 2 (IL-2).

3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment with regular MRIs and assessments.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Radiotherapy
• Standard of Care
• Temozolomide
• TVI-Brain-1

Trial Overview The study tests TVI-Brain-1 immunotherapy combined with standard care versus standard care alone in treating glioblastoma. It involves creating a personalized vaccine from the patient's cancer cells to boost immune response and infusing expanded T cells back into the patient.

How Is the Trial Designed?

Group I: Interventional TVI-Brain-1 Autologous Vaccine and activated autologous blood-derived t cells Experimental Treatment 4 Interventions

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.

Group II: Standard of Care Active Control 3 Interventions

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.

Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in United States as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Canada as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Japan as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in China as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Approved in Switzerland as Radiation therapy for:

• Various cancers including breast cancer, lung cancer, prostate cancer, and soft tissue sarcoma

Who Is Running the Clinical Trial?

TVAX Biomedical

Lead Sponsor

Trials

4

Recruited

150+

FDA Office of Orphan Products Development

Collaborator

Trials

73

Recruited

6,400+

Published Research Related to This Trial

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

The combination of fractionated radiotherapy and temozolomide (TMZ), followed by autologous formalin-fixed tumor vaccine (AFTV), was well tolerated in 24 patients with newly diagnosed glioblastoma multiforme (GBM), showing promising safety and efficacy.

One-third of the patients experienced progression-free survival (PFS) of 24 months or more, with a median overall survival (OS) of 22.2 months, indicating that this treatment regimen may enhance antitumor immunity and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma. Ishikawa, E., Muragaki, Y., Yamamoto, T., et al.[2023]

In a study of 165 glioblastoma patients, the extent of tumor resection was the only factor associated with longer survival, indicating that surgical removal of the tumor is crucial for improving outcomes.

The use of Gliadel wafers significantly increased the risk of adverse events, especially in patients with recurrent tumors, with those receiving eight wafers facing a 3-fold higher risk of adverse events and a 5.6-fold higher risk of site-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma. De Bonis, P., Anile, C., Pompucci, A., et al.[2018]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

Temozolomide is a chemotherapeutic agent that effectively crosses the blood-brain barrier and has shown a good safety profile in treating brain metastases from solid tumors, with clinical activity observed in heavily pretreated patients.

In a randomized phase II trial, temozolomide combined with radiation therapy resulted in a significantly higher objective response rate (96% vs. 67%) compared to radiation alone, particularly benefiting patients with newly diagnosed brain and lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide for treating brain metastases. Abrey, LE., Christodoulou, C.[2019]

Whole-brain radiotherapy (WBRT) combined with temozolomide (TMZ) significantly improves the objective response rate in patients with brain metastases from non-small-cell lung cancer (NSCLC), with a relative risk of 1.43 based on a meta-analysis of 25 clinical trials.

However, this combination treatment also increases the risk of severe hematological (grade III-IV) and gastrointestinal toxicities compared to WBRT alone, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis. Han, J., Qiu, M., Su, L., et al.[2022]

In a study involving 3 glioblastoma multiforme (GBM) patients, the combination of autologous formalin-fixed tumor vaccine (AFTV) and temozolomide (TMZ) showed promising results, with two patients exhibiting a partial response to treatment after therapy.

The therapy was well-tolerated with only minor adverse effects, and it led to increased CD3(+)CD8(+) lymphocytes in surgical specimens, suggesting an enhanced immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological changes after autologous formalin-fixed tumor vaccine therapy combined with temozolomide for glioblastoma - three case reports - . Sakamoto, N., Ishikawa, E., Yamamoto, T., et al.[2022]

In a study of 27 patients with newly diagnosed high-grade gliomas, the combination of temozolomide (TMZ) and radiation therapy (RT) demonstrated promising efficacy, with a median overall survival of 19 months and a one-year survival rate of 81.2%.

The treatment was well tolerated with no drug toxicity-related mortality, indicating a favorable safety profile, especially in patients under 50 years old and those who had debulking surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. Shawky, H., Abo Hamar, AH., Galal, S., et al.[2020]

Temozolomide (tmz), a common chemotherapy drug for glioblastoma, can cause cutaneous drug eruptions, which are rare side effects that have not been widely reported.

In two cases studied, one patient showed clinical signs of an allergy to tmz without positive tests, while the second case confirmed the allergy through a positive lymphocyte activation test, highlighting the need for awareness of potential dermatologic reactions during tmz treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma. Deluche, E., Leobon, S., Touraine, F., et al.[2018]

Temozolomide (TMZ) enhances the effectiveness of radiation therapy in treating glioblastoma cells, leading to a significant reduction in colony formation when combined with irradiation, compared to either treatment alone.

While irradiation was more toxic to glioma cells than TMZ, the combination of both treatments increased the sensitivity of glioma cells to radiation, suggesting a potential strategy for improving glioblastoma treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. Babaloui, S., Najafi, M., Mozdarani, H., et al.[2022]

In a phase II study involving 30 patients with brain metastases from non-small cell lung cancer (NSCLC), temozolomide (TMZ) was found to be an active and safe treatment option, with 10% of patients achieving an objective response, including two complete remissions.

No severe (grade 3 or 4) toxicities were reported, and all treatment-related adverse events were mild to moderate, indicating that TMZ can be administered without significant safety concerns in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Giorgio, CG., Giuffrida, D., Pappalardo, A., et al.[2018]

Concurrent treatment with temozolomide (TMZ) and radiation therapy (RT) significantly improves survival in patients with glioblastoma multiforme (GBM), particularly in tumors with O6-methylguanine-DNA methyltransferase (MGMT) methylation, showing a median survival ratio of 5.7 compared to 2.3 for unmethylated tumors.

The study found that only a subset of MGMT methylated tumors benefits from the combined therapy, while sequential treatment of RT followed by TMZ is less effective than concurrent administration, highlighting the importance of treatment timing and tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitizing effects of temozolomide observed in vivo only in a subset of O6-methylguanine-DNA methyltransferase methylated glioblastoma multiforme xenografts. Carlson, BL., Grogan, PT., Mladek, AC., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01081223

NCT01081223 | Phase I/II Study To Test The Safety and ... The study is designed to determine whether vaccinating recurrent grade IV glioma subjects four times with attenuated cancer cells stimulates more powerful ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05685004

Study of Neoantigen-specific Adoptive T Cell Therapy for ... 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

3. tvaxbiomedical.com tvaxbiomedical.com/tvi-brain-1/

TVI-Brain-1 for the Treatment of Glioblastoma Results of these studies demonstrated significantly increased median survival for patients treated with TVAX Immunotherapy as compared to historical controls.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12310467/

cancer vaccines as novel therapeutic strategies for brain tumor Subgroup analysis revealed particularly favorable outcomes in patients with recurrent glioblastoma, who demonstrated a median OS of 966 days (~32 months) and a ...

5. synapse.patsnap.com synapse.patsnap.com/drug/c19cb955e7d54cf3a1b2fb0f5104cb0a

TVI Brain 1 - Drug Targets, Indications, Patents Phase 2 study to test the safety and efficacy of TVI-Brain-1 as a treatment for recurrent grade IV glioma.

6. trial.medpath.com trial.medpath.com/clinical-trial/56c326407422f620/safety-efficacy-tvi-brain-1-glioma

Phase I/II Study To Test The Safety and Efficacy of TVI-Brain-1 ... The study is designed to determine whether vaccinating recurrent grade IV glioma subjects four times with attenuated cancer cells stimulates more powerful ...