GBM Vaccine for Glioblastoma

Recruiting at 10 trial locations

Overseen By Seema Nagpal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VBI Vaccines Inc.

Must not be taking: Immunosuppressants, Antivirals

Disqualifiers: Active infection, Cancer history, Autoimmune, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Variable, until tumor progression

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new vaccine called VBI-1901 for patients whose brain cancer, glioblastoma, has returned. The vaccine aims to help the immune system recognize and fight the cancer cells. Researchers are checking if the vaccine is safe and finding the best dose to use.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not be on immunosuppressive agents within 4 weeks prior to starting the treatment. It's best to discuss your current medications with the study team to ensure they are compatible with the trial requirements.

Is the GBM Vaccine for Glioblastoma safe for humans?

The safety of the GBM Vaccine for Glioblastoma, including versions like VBI-1901, has been evaluated in various studies. These studies generally focus on the safety of similar vaccines in humans, showing that they are feasible and safe, with some adverse events reported but not detailed in the provided abstracts. ^{1 2 3 4 5}

How is the GBM Vaccine for Glioblastoma treatment different from other treatments?

The GBM Vaccine for Glioblastoma, using VBI-1901, is unique because it employs virus-like particles (eVLPs) to stimulate the immune system to target and attack glioblastoma cells, offering a novel approach compared to traditional treatments like surgery, radiation, and chemotherapy. ^{1 2 4 6 7}

What data supports the effectiveness of the treatment VBI-1901 for Glioblastoma?

While there is no direct data on VBI-1901, other vaccine-based treatments for Glioblastoma have shown promise in prolonging survival and progression-free survival in clinical trials. These treatments work by triggering the immune system to target and fight tumor cells, offering hope for improved outcomes in this aggressive cancer. ^{1 2 3 4 7}

Who Is on the Research Team?

Francisco Diaz-Mitoma, MD

Principal Investigator

Variation Biotechnologies Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with recurrent glioblastoma (GBM) who've had initial treatment including surgery and radiation, possibly with chemotherapy. They must have stable or decreasing corticosteroid use, recovered from prior treatments, no large or multi-focal tumors on MRI, and adequate organ function. Women of childbearing age need a negative pregnancy test and agree to contraception.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

I take 4mg or less of corticosteroids daily.

Agreement to use acceptable contraception for sexually active subjects

Exclusion Criteria

Lack of family or social support structure

Contrast-enhancing residual tumor associated with dissemination

Evidence of HCMV viremia above specified levels

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VBI-1901 vaccine every 4 weeks until tumor progression

Variable, until tumor progression

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Extension

Continuation of optimal dose level in recurrent GBM subjects

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• VBI-1901

Trial Overview The study tests the safety and tolerability of VBI-1901 vaccine in combination with standard chemotherapy drugs Carmustine or Lomustine in patients with recurrent GBM. It aims to find the optimal dose of VBI-1901 by gradually increasing it among participants while monitoring their reactions.

How Is the Trial Designed?

Group I: Part C VBI-1901 with GM-CSF Adjuvant Experimental Treatment 1 Intervention

VBI-1901 10 μg HCMV pp65 formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal ID injections.

Group II: Part B GM-CSF Adjuvant Experimental Treatment 1 Intervention

VBI-1901 10 μg HCMV pp65 formulated with GM-CSF (200 μg) in 0.2 to 0.4 mL volume, given in two to four equal ID injections.

Group III: Part B AS01B Adjuvant Experimental Treatment 1 Intervention

VBI-1901 10 μg HCMV pp65 formulated with AS01B (50 μg of QS-21 and 50 μg of MPL per dose) in 1.0 mL volume, given in one IM injection

Group IV: Part A Dose Level 3 Experimental Treatment 1 Intervention

VBI-1901 high dose (10 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Group V: Part A Dose Level 2 Experimental Treatment 1 Intervention

VBI-1901 intermediate dose (2 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Group VI: Part A Dose Level 1 Experimental Treatment 1 Intervention

VBI-1901 low dose (0.4 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Group VII: Part C Standard of Care Treatment Active Control 2 Interventions

Single-agent standard-of-care (SOC) treatment with either carmustine intravenously at a dose of 150 mg/m² or lomustine orally at a dose of 110 mg/m² (up to a maximum dose of 200 mg).

VBI-1901 is already approved in United States for the following indications:

Approved in United States as VBI-1901 for:

• Recurrent glioblastoma

Who Is Running the Clinical Trial?

VBI Vaccines Inc.

Lead Sponsor

Trials

12

Recruited

5,700+

Published Research Related to This Trial

In a study involving 21 patients with recurrent glioblastoma (rGBM), the therapeutic vaccine SITOIGANAP combined with other treatments resulted in a median progression-free survival of 9.14 months and a median overall survival of 19.63 months, indicating a significant survival benefit.

The treatment showed minimal toxicity compared to current therapies, with 48% of patients receiving at least six cycles achieving a median overall survival of 30.64 months and a 1-year survival rate of 90%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Cohort Study of SITOIGANAP to Treat Glioblastoma When Given in Combination With Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Nivolumab or Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Pembrolizumab in Patients Who Failed Prior Treatment With Surgical Resection, Radiation, and Temozolomide. Bota, DA., Taylor, TH., Lomeli, N., et al.[2022]

The AV-GBM-1 vaccine was successfully manufactured for all 63 patients in the trial, demonstrating a high success rate of 97% for tumor cell production and monocyte collection, which is crucial for its effectiveness.

While the treatment was generally well-tolerated, with common side effects including local injection reactions and flu-like symptoms, it also led to significant central nervous system adverse events, such as seizures and headaches, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. Bota, DA., Taylor, TH., Piccioni, DE., et al.[2023]

Immunotherapy using tumor vaccines shows promise in treating glioblastoma (GBM), a highly aggressive brain tumor, by potentially triggering specific immune responses against tumor cells.

Ongoing and upcoming phase III trials of various GBM vaccines could lead to significant improvements in patient survival, making immunotherapy a standard treatment option if proven effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current vaccine trials in glioblastoma: a review. Xu, LW., Chow, KK., Lim, M., et al.[2021]

Glioblastoma is a very aggressive brain tumor with a poor prognosis, often leading to a median survival of less than 2 years despite aggressive treatment, highlighting the need for new therapeutic strategies.

Recent clinical trials of vaccine-based immunotherapies have shown promise in improving progression-free and overall survival in glioblastoma patients, suggesting a potential new avenue for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-Based Immunotherapeutics for the Treatment of Glioblastoma: Advances, Challenges, and Future Perspectives. Cuoco, JA., Benko, MJ., Busch, CM., et al.[2018]

Anti-gene vaccines targeting the growth factor IGF-I, specifically using antisense (AS) and triple helix (TH) approaches, have been shown to significantly increase median survival in glioblastoma (GBM) patients, with some patients surviving up to 2-3 years.

The TH vaccines demonstrated stronger immunogenicity and a more robust immune response compared to AS vaccines, leading to improved outcomes in terms of patient survival, with median survival extending to 17-18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. Trojan, A., Lone, YC., Briceno, I., et al.[2023]

In a study involving 23 glioblastoma patients, vaccination with a virus-modified autologous tumor cell vaccine was found to be safe, with no severe side effects reported, and it significantly improved median progression-free survival (40 weeks vs. 26 weeks in controls) and overall survival (100 weeks vs. 49 weeks in controls).

The vaccination led to a notable increase in antitumor immune responses, evidenced by higher levels of tumor-reactive memory T cells and CD8(+) tumor-infiltrating T-lymphocytes, suggesting that the vaccine not only enhances survival but also stimulates the immune system to fight the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. Steiner, HH., Bonsanto, MM., Beckhove, P., et al.[2021]

Immunotherapy, particularly through vaccination, has emerged as a promising approach to stimulate the immune response against glioblastoma, a highly aggressive brain tumor, but has yet to show success in phase III clinical trials.

Current strategies include peptide vaccines targeting specific tumor antigens and cell-based vaccines, but despite positive results in earlier trials, no definitive phase III outcomes have been achieved, highlighting the need for further research and potential combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination in the immunotherapy of glioblastoma. Kong, Z., Wang, Y., Ma, W.[2023]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Prospective, Cohort Study of SITOIGANAP to Treat Glioblastoma When Given in Combination With Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Nivolumab or Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Pembrolizumab in Patients Who Failed Prior Treatment With Surgical Resection, Radiation, and Temozolomide. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment. [2023]

3. Egypt pubmed.ncbi.nlm.nih.gov

Current vaccine trials in glioblastoma: a review. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Vaccine-Based Immunotherapeutics for the Treatment of Glioblastoma: Advances, Challenges, and Future Perspectives. [2018]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Vaccination in the immunotherapy of glioblastoma. [2023]