Pembrolizumab + Optune GIO® + NeuroBlate® for Glioblastoma

(OPTIMUS PRIME Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Ashley Ghiaseddin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Florida

Must be taking: Pembrolizumab

Must not be taking: Anti-angiogenics, Anti-PD-1

Disqualifiers: Immunodeficiency, Active autoimmune, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

In this study we are evaluating the safety and feasibility of the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent or progressive glioblastoma (GBM) WHO Grade IV, IDH wild type or recurrent or progressive astrocytoma WHO grade IV.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain treatments like anti-angiogenic agents or specific immunotherapies before joining. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Pembrolizumab + Optune GIO® + NeuroBlate® for Glioblastoma?

Research shows that pembrolizumab, a part of this treatment, can enhance immune responses and improve survival in patients with recurrent glioblastoma when given before surgery. This suggests that pembrolizumab may help the body's immune system fight the tumor more effectively. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Optune GIO®, and NeuroBlate® safe for humans?

Pembrolizumab, a part of this treatment, has been shown to be generally safe in humans, with common side effects like tiredness, rash, itching, and diarrhea, and less common effects like thyroid issues, inflammation of the colon, liver, and lungs. However, specific safety data for the combination with Optune GIO® and NeuroBlate® is not available in the provided research. ^{1 3 6 7 8}

How is the treatment with Pembrolizumab + Optune GIO® + NeuroBlate® for glioblastoma different from other treatments?

This treatment is unique because it combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with Optune GIO®, a device that uses electric fields to disrupt cancer cell growth, and NeuroBlate®, a laser therapy that targets and destroys tumor tissue. This multi-modal approach aims to enhance the effectiveness of treatment for glioblastoma, a condition with limited standard treatment options. ^{1 2 3 4 6}

Research Team

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Eligibility Criteria

Adults with recurrent or progressive glioblastoma (a type of brain tumor) can join this trial. They must have had a recent MRI, not received certain previous treatments, and be physically able to undergo the procedures. The trial excludes those who've had specific anti-angiogenic agents.

Inclusion Criteria

I am 18 years old or older.

My condition is a type of brain cancer called glioblastoma or grade IV astrocytoma.

My brain tumor has grown, as confirmed by MRI, and I haven't used anti-angiogenic drugs except in specific cases.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the triple combination of Optune GIO®, MLA, and pembrolizumab. Treatment includes pre-MLA Optune GIO® for 3-10 days, MLA, and post-MLA Optune GIO® with pembrolizumab every 3 weeks.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with ongoing safety assessments and monitoring for disease progression or intolerable toxicity.

3 months

Treatment Details

Interventions

• NeuroBlate® (Device)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study tests combining three treatments for brain tumors: TTFields therapy using Optune GIO®, laser ablation surgery with NeuroBlate®, and an immunotherapy drug called Pembrolizumab. It aims to see if they're safe when used together.

Participant Groups

Group I: Arm 2: Optune GIO®+Pembrolizumab pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA Experimental Treatment 3 Interventions

Patients randomized to treatment arm 2, will start treatment with Optune GIO® for 3-10 days and receive one infusion of pembrolizumab before undergoing MLA/biopsy. Patients will resume Optune GIO® no earlier than 10 days post-surgery and receive pembrolizumab 200 mg IV every 3 weeks (+/- 4 days) starting no sooner than 1 week after the start of Optune GIO®.

Group II: Arm 1: Optune GIO® pre-MLA; MLA; followed by Optune GIO® + Pembrolizumab post MLA Experimental Treatment 3 Interventions

Patients randomized to treatment arm 1 will start treatment with Optune GIO® for 3-7 days and undergo MLA and biopsy for tumor diagnosis and immune monitoring. Treatment with Optune GIO® will be paused prior to the MLA procedure until at least 10 days post MLA. Patients will then resume treatment with Optune GIO® and receive pembrolizumab 200 mg IV every 3 weeks (+/- 4 days) starting no sooner than 1 week after the start of Optune GIO®.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UF Health Shands Hospital Gainesville, FL

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1428

Patients Recruited

987,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Nayak, L., Molinaro, AM., Peters, K., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. de Groot, J., Penas-Prado, M., Alfaro-Munoz, K., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Cloughesy, TF., Mochizuki, AY., Orpilla, JR., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Goldberg, SB., Gettinger, SN., Mahajan, A., et al.[2022]

References

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

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. [2021]

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

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]

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

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]