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 tests a new vaccine, VBI-1901, to determine its safety and tolerability in people with glioblastoma, a type of brain cancer. The trial consists of different parts, each assessing various doses of the vaccine or its combination with other treatments. Individuals whose glioblastoma has recurred after treatment and who have a stable condition might qualify for this study. Participants must have a confirmed glioblastoma diagnosis and show evidence of cancer recurrence. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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

Research has shown that VBI-1901 is generally safe and well-tolerated in people. Studies with glioblastoma patients (a type of brain cancer) found that this vaccine, particularly with the GM-CSF booster, did not cause severe side effects. Reports from previous trials indicated that this combination helped control the disease without major negative effects. Additionally, using VBI-1901 with the AS01B booster has also been reported as safe and well-tolerated. These findings suggest that VBI-1901 could be a safe option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about VBI-1901 for glioblastoma because it introduces a novel approach using a vaccine to stimulate the immune system against the tumor. Unlike standard chemotherapies like carmustine or lomustine, VBI-1901 is designed to enhance the body's immune response by using a human cytomegalovirus (HCMV) antigen, specifically pp65, formulated with adjuvants like GM-CSF or AS01B. This method aims to harness the body's immune system to target and attack cancer cells directly, offering a potentially more precise and less toxic alternative to traditional treatments. Such an approach could lead to improved outcomes with fewer side effects, sparking hope among researchers for more effective glioblastoma management.

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

Research has shown that VBI-1901, which participants in this trial may receive, can boost the immune system in patients with recurrent glioblastoma, a type of brain cancer. Studies indicate a 43% disease control rate, meaning nearly half of the patients experienced stable disease or improvement. This vaccine is designed to help the immune system recognize and attack cancer cells by targeting specific proteins. Early findings suggest it can help control tumor growth by strengthening the body's natural defenses. These initial results are promising for those considering this treatment option. ^{1 2 6 7 8}

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.

Agreement to use acceptable contraception for sexually active subjects

Tumor specimen available for central pathological review

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

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]

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]

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]

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]

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]

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. vbivaccines.com vbivaccines.com/press-releases/vbi-vaccines-announces-new-tumor-response-data-from-ongoing-randomized-controlled-phase-2b-study-of-vbi-1901-in-recurrent-glioblastoma-patients/

VBI Vaccines Announces New Tumor Response Data ... VBI-1901's ability to stimulate an immune response capable of generating a disease control rate of 43% at this interim stage of the study, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03382977

NCT03382977 | Study to Evaluate Safety, Tolerability, and ... The purpose of this study is to assess the safety and tolerability of VBI-1901 in subjects with recurrent malignant gliomas (glioblastoma, or GBM).

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2014

Evaluation of tumor responses and overall survival in ... Evaluation of GM-CSF and AS01B adjuvants in a phase I/IIa trial of a therapeutic CMV vaccine (VBI-1901) against recurrent glioblastoma (GBM).

4. biospace.com biospace.com/vbi-vaccines-announces-new-tumor-response-data-from-ongoing-randomized-controlled-phase-2b-study-of-vbi-1901-in-recurrent-glioblastoma-patients

VBI Vaccines Announces New Tumor Response Data from ... VBI-1901's ability to stimulate an immune response capable of generating a disease control rate of 43% at this interim stage of the study, ...

5. synapse.patsnap.com synapse.patsnap.com/article/early-positive-results-from-vbi-1901-phase-2b-study-in-recurrent-glioblastoma

Early Positive Results from VBI-1901 Phase 2b Study in ... In the active study arm, two stable diseases have been observed, achieving a 40% early DCR. However, in the control arm, no tumor responses were ...

6. vbivaccines.com vbivaccines.com/wp-content/uploads/2022/02/VBI-1901_B-Riley-Oncology-Conference-January-2022.pdf

Development of eVLP Platform for Viral Associated Cancers optimal therapeutic dose level of VBI-1901 in recurrent GBM patients ... • VBI-1901 + AS01B is safe and well tolerated. • 5/10 tumor ...

7. sec.gov sec.gov/Archives/edgar/data/764195/000149315220021995/ex99-2.htm

VBI Vaccines Announces Positive Interim Phase 2a Data ... Interim data show promising disease control rates in patients vaccinated with VBI-1901 combined with the GM-CSF adjuvant (40%), ...

8. firstwordpharma.com firstwordpharma.com/story/5802740

VBI Vaccines Presents Additional Biomarker Data from ... VBI Vaccines Presents Additional Biomarker Data from Phase 1/2a Study of VBI-1901 in Recurrent GBM at the 2023 Society for Neuro-Oncology (SNO) ...