Combination Immunotherapy for Glioblastoma

Not currently recruiting at 41 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether IGV-001, a new treatment, can help people newly diagnosed with glioblastoma (an aggressive brain cancer) live longer without disease progression. Participants will receive either the experimental IGV-001 treatment alongside standard therapies like radiation and temozolomide (a chemotherapy drug) or a placebo instead of IGV-001. This trial may suit those recently diagnosed with glioblastoma in the brain's upper regions (supratentorial compartment) who have not undergone prior surgery or treatment for the cancer. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that IGV-001 is generally safe for people. A recent study found no new risks when comparing IGV-001 to the usual treatment for glioblastoma, a type of brain cancer. Participants who received IGV-001 did not experience unexpected or severe side effects compared to those on standard treatments. While the study noted serious side effects, they were not more common than those typically expected with current treatments. Thus, IGV-001 appears to be well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for glioblastoma?

Researchers are excited about IGV-001 for glioblastoma because it introduces a novel approach by using biodiffusion chambers to deliver the treatment directly to the tumor site. This method differs from the standard of care, which typically involves radiation and the chemotherapy drug temozolomide. IGV-001’s unique delivery system allows for targeted therapy, potentially enhancing effectiveness and minimizing side effects. By concentrating the treatment at the tumor, it may offer a more direct attack on cancer cells, promising quicker and more significant results than traditional systemic treatments.

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

Research has shown that IGV-001, one of the treatments studied in this trial, may help treat glioblastoma, a type of brain cancer. In an earlier study, patients with newly diagnosed glioblastoma tolerated IGV-001 well, and it showed several signs of effectiveness. Another study found that IGV-001 had a good balance of benefits and risks, with no new dangers compared to standard treatments. IGV-001 is a personalized treatment that helps the immune system attack cancer cells, first proven effective in animal studies. These findings suggest that IGV-001 could be a promising option for improving survival in glioblastoma patients. ^{2 6 7 8 9}

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

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]

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 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 (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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10639175/

CTIM-17. ADDITIONAL RESULTS FROM A PHASE 1B ... IGV-001 was well tolerated and multiple efficacy signals were observed in a Phase 1b study in patients with ndGBM (Andrews et al., 2021).

2. onclive.com onclive.com/view/igv-001-showcases-positive-benefit-risk-profile-in-newly-diagnosed-glioblastoma

IGV-001 Showcases Positive Benefit-Risk Profile in Newly ... Blinded safety data showed that IGV-001 led to no new risks compared with standard of care in a phase 2b trial for glioblastoma, with 86 serious ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04485949

Study Details | NCT04485949 | A Phase 2b ... The purpose of this study is to assess progression-free survival (PFS) and overall survival (OS) in newly diagnosed Glioblastoma (GBM) participants treated with ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/27/7/1912/671878/Phase-Ib-Clinical-Trial-of-IGV-001-for-Patients

Phase Ib Clinical Trial of IGV-001 for Patients with Newly ... We believe IMV-001, in the siRNA class, serves as the most effective proapoptotic stimulus stressing malignant glioma cells (27) and also ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1556450/full

IGV-001 cellular immunotherapy for newly diagnosed ... IGV-001 is a personalized, autologous cellular immunotherapy for glioblastoma. Its anti-tumor efficacy was initially demonstrated in mouse models using ...

6. imvax.com imvax.com/wp-content/uploads/2024/10/EANO-Ph2b_EarlySafety-Poster_9Oct2024_final.pdf

Early Safety Data From a Randomized, Multicenter, Double ... BDCs are irradiated, producing IGV-001, which is implanted into 2 abdominal sites (between the rectus abdominis muscle and fascia) of patients ...

7. endbraincancer.org endbraincancer.org/2024/12/imvax-igv-001-new-safety-data/

IMVAX IGV-001 New Safety Data Imvax presented blind safety data from the company's ongoing randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial ...

8. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii88/7890496

Neuro-Oncology | Oxford Academic After surgical resection, subjects were randomized 2:1 and treated with IGV-001 or placebo followed by SOC. The primary outcome is PFS, defined ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38060340/

Autologous cell immunotherapy (IGV-001) with IGF-1R ... The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed ...