Combination Immunotherapy for Glioblastoma

Recruiting at 39 trial locations

Overseen By Jill Krause

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Imvax

Must not be taking: Investigational agents, Tumor Treating Fields

Disqualifiers: Bi-hemispheric disease, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 41 weeks

93 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to assess progression-free survival (PFS) and overall survival (OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with placebo.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are receiving treatment with Tumor Treating Fields or Optune®, you cannot participate in the trial.

Is the combination immunotherapy for glioblastoma safe?

Temozolomide, a drug used in combination with radiotherapy for glioblastoma, generally has a lower toxicity compared to older chemotherapy drugs, but rare cases of serious blood disorders like therapy-related acute myeloid leukemia have been reported. ^{1 2 3 4 5}

What makes the combination immunotherapy treatment IGV-001 unique for glioblastoma?

The combination immunotherapy treatment IGV-001 is unique because it uses a patient's own glioblastoma tumor cells combined with an antisense oligonucleotide (a small piece of DNA or RNA designed to bind to specific molecules) against the IGF type 1 receptor, aiming to enhance the immune response against the tumor, which is different from standard treatments that typically involve only radiation and chemotherapy. ^{1 3 5 6 7}

What data supports the effectiveness of the drug Temozolomide for glioblastoma?

Research shows that combining Temozolomide with radiotherapy improves survival rates in glioblastoma patients, especially when the MGMT promoter is methylated. Additionally, Temozolomide with intensity modulated radiation therapy enhances immune function and overall treatment effectiveness in glioma patients. ^{1 5 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals newly diagnosed with Glioblastoma (WHO Grade III or IV). They must have a measurable brain lesion, test positive for certain antigens, have good organ function and performance status (KPS score ≥ 70), and the tumor should be in the supratentorial compartment. Excluded are those with bi-hemispheric disease, prior GBM treatments, other cancers within 3 years (with exceptions), severe immune conditions, heart issues, recent live vaccines or active infections.

Inclusion Criteria

I have had a specific brain scan showing a measurable tumor.

I have had a specific brain scan showing a measurable lesion.

My organs and bone marrow are working well.

Exclusion Criteria

Is partaking in another interventional study. Participants who are partaking in an observational study are eligible

My MRI shows cancer has spread to both sides of my brain, brain stem, or cerebellum.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Participants are implanted with biodiffusion chambers containing IGV-001 or placebo on Day 1 and explanted on Day 3

3 days

1 visit (in-person)

Treatment

Participants receive radiotherapy per institutional standards for 5 days per week along with temozolomide for up to 12 weeks, followed by temozolomide on Days 1 to 5 of each 28-day cycle for up to 6 cycles

41 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• IGV-001
• Placebo
• Standard of Care (SOC): Radiation Therapy
• Temozolomide

Trial Overview The study tests IGV-001 Cell Immunotherapy against a placebo in patients with Glioblastoma to see if it improves progression-free survival (PFS) and overall survival (OS). All participants will also receive standard care including radiation therapy and Temozolomide chemotherapy.

How Is the Trial Designed?

Group I: IGV-001 Experimental Treatment 3 Interventions

Participants will be implanted with biodiffusion chambers containing IGV-001 on Day 1 and explanted on Day 3 (at approximately 48 hours following implantation). After 6 weeks, participants will receive radiotherapy (RT) per institutional standards for 5 days per week along with temozolomide 75 mg/m\^2 orally, once daily (QD) for up to 12 weeks followed by temozolomide 150 to 200 mg/m\^2, orally, on Days 1 to 5 of each 28-day cycle for up to 6 cycles (Week 41).

Group II: Placebo Placebo Group 3 Interventions

Participants will be implanted with biodiffusion chambers containing placebo on Day 1 and explanted on Day 3 (at approximately 48 hours following implantation). After 6 weeks, participants will receive RT per institutional standards for 5 days per week along with temozolomide 75 mg/m\^2 orally, QD for up to 12 weeks followed by temozolomide 150 to 200 mg/m\^2, orally, on Days 1 to 5 of each 28-day cycle for up to 6 cycles (Week 41).

Who Is Running the Clinical Trial?

Imvax

Lead Sponsor

Trials

1

Recruited

90+

Published Research Related to This Trial

In a phase III study involving 716 patients with newly diagnosed glioblastoma, the addition of the immune checkpoint inhibitor nivolumab (NIVO) to standard radiotherapy (RT) and temozolomide (TMZ) did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to placebo, with median OS of 28.9 months for NIVO versus 32.1 months for placebo.

The study found a higher rate of grade 3/4 treatment-related adverse events in the NIVO group (52.4%) compared to the placebo group (33.6%), indicating that while NIVO did not enhance efficacy, it was associated with increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Lim, M., Weller, M., Idbaih, A., et al.[2023]

In a study of 103 glioblastoma patients treated with standard temozolomide and radiotherapy, the median overall survival was found to be 13.7 months, highlighting the effectiveness of this treatment regimen.

Three key prognostic factors were identified that negatively impacted overall survival: age over 65 years, a Medical Research Council (MRC) scale score of 3-4, and the occurrence of postoperative complications, suggesting that these factors can help predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. Verlut, C., Mouillet, G., Magnin, E., et al.[2020]

In a study of 79 patients with glioblastoma, the combination of radiotherapy and temozolomide resulted in a median overall survival of 18.3 months and 2-year survival rate of 37.1%, which aligns with previous international studies.

The main side effect observed was hematologic toxicity in 8.8% of patients, indicating that while the treatment is effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. Jeon, HJ., Kong, DS., Park, KB., et al.[2018]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, 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 (TMZ) is commonly used as an adjuvant therapy for malignant glioma, but in this case study, a patient developed treatment-related acute myeloid leukemia (t-AML) after receiving 15 cycles of TMZ, highlighting a rare but serious complication.

The case raises questions about the duration of TMZ therapy, as the patient showed no tumor progression but still developed t-AML, suggesting a need for better guidelines to balance treatment benefits and risks in long-term TMZ use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. Kosugi, K., Saito, K., Takahashi, W., 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. [2023]

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

Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. [2023]

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

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience. [2018]

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

Effect of Temozolomide Combined with Intensity Modulated Radiation Therapy on Serum Factor, Immune Function and Clinical Efficacy in Postoperative Glioma Patients. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]

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

Future directions for temozolomide therapy. [2019]

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

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma. [2018]

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

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma. [2023]

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

Phase Ib Clinical Trial of IGV-001 for Patients with Newly Diagnosed Glioblastoma. [2022]