Pembrolizumab + Optune GIO® + NeuroBlate® for Glioblastoma

(OPTIMUS PRIME Trial)

Overseen By Victoria Hope

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

20 Participants Needed

What You Need to Know Before You Apply

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.

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 2 3 4 5}

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 6 7}

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 6 7 8}

Who Is on the Research Team?

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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

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.

I had a special brain scan within the last 28 days.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• NeuroBlate®
• Pembrolizumab

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.

How Is the Trial Designed?

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®.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

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]

In a phase II study involving 80 patients with recurrent glioblastoma, pembrolizumab combined with bevacizumab showed a 6-month progression-free survival (PFS-6) of 26% and a median overall survival (OS) of 8.8 months, indicating limited efficacy despite being well tolerated.

Pembrolizumab alone had a much lower PFS-6 of 6.7% and no objective responses, suggesting that while the combination therapy had some durable responses, neither treatment was effective enough for significant clinical benefit.

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]

In a phase II trial involving 15 patients with recurrent glioblastoma, pembrolizumab treatment did not lead to significant immune activation within the tumor microenvironment, which was characterized by a lack of T cells and a predominance of CD68+ macrophages.

Despite no treatment-related deaths and a median overall survival of 20 months, the study found that pembrolizumab alone was insufficient to induce a robust immune response in most patients, suggesting that additional strategies may be needed to enhance its efficacy in glioblastoma.

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]

In a clinical trial involving 35 patients with recurrent glioblastoma, those who received neoadjuvant therapy with pembrolizumab before surgery showed significantly longer overall survival compared to those who only received adjuvant therapy after surgery.

Neoadjuvant treatment was linked to beneficial changes in the tumor's immune environment, including increased T cell activity and reduced cell-cycle-related gene expression, suggesting that this approach may enhance the body's immune response against glioblastoma more effectively than post-surgical treatment alone.

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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

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]

Citations

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]