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?

This trial tests a new combination of treatments for individuals with recurring or worsening glioblastoma, an aggressive brain cancer. Researchers aim to determine the safety and feasibility of using Optune GIO® (a device delivering electrical fields to the brain) and pembrolizumab (an immune therapy drug) with NeuroBlate® (a laser treatment). Participants are divided into two groups: one begins with Optune GIO® alone, while the other starts with both Optune GIO® and pembrolizumab before the laser procedure. Ideal candidates are adults whose glioblastoma has returned or worsened and who have not previously used certain cancer drugs. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

Previous studies have used the combination of pembrolizumab with TTFields (Tumor Treating Fields) to treat brain tumors. This combination has demonstrated a stronger immune response and some improvement in delaying tumor growth. While pembrolizumab alone has limited effects, it appears more effective when combined with other treatments.

Regarding safety, pembrolizumab is generally well-tolerated but can cause side effects such as tiredness, skin rash, or fever. People with glioblastoma who used this drug in combination with other therapies rarely experienced severe side effects.

NeuroBlate, a laser treatment for brain tumors, has been shown to be generally safe, though some risks exist. The most common issues were seizures (2%), muscle weakness (1.5%), and wound infections (1.5%). These complications are rare, and serious problems like bleeding were even less common at 0.5%.

Overall, both treatments have a safety record suggesting they are well-tolerated by most patients, but like any medical treatment, some risks are involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine innovative technologies with an established immunotherapy to tackle glioblastoma, a notoriously aggressive brain cancer. Optune GIO® uses electric fields to disrupt cancer cell division, offering a unique approach compared to traditional chemotherapy or radiation. Paired with pembrolizumab, an immunotherapy that helps the immune system recognize and attack cancer cells, this combination aims to enhance treatment efficacy. By integrating tumor-treating fields and immune checkpoint blockade, this approach could potentially improve patient outcomes more effectively than current standard treatments, which rely primarily on surgery, radiation, and temozolomide.

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

This trial will evaluate the combination of pembrolizumab with Optune GIO for treating glioblastoma. Research has shown that using pembrolizumab with Optune GIO may improve progression-free survival (PFS) in patients. In some cases, this combination has led to strong disease control, with some patients experiencing almost complete recovery. Specifically, Optune GIO in this combination has helped patients with recurring glioblastoma live longer. These findings suggest that this treatment combination could effectively manage this challenging condition. Participants in this trial will be randomized into two treatment arms to assess the effectiveness of these combinations. ^{6 7 8 9 10}

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 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]

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 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 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 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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025001357

Efficacy and safety of adjuvant TTFields plus ... This study confirms that the use of TTFields in conjunction with pembrolizumab enhances immune recognition and anti-tumor immunity, significantly improving PFS ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10695547/

Efficacy of tumour-treating fields therapy in recurrent ... In the context of recurrent GBM, Optune has improved survival and fewer adverse effects than conventional treatment. Nevertheless, long-term ...

3. immunitybio.com immunitybio.com/initial-data-shows100-disease-control-in-5-out-of-5-patients-with-recurrent-glioblastoma-with-two-patients-in-near-complete-response-treated-with-immunitybios-anktiva-nk-cell-therapy-p/

Initial Data Shows 100% Disease Control in 5 Out of 5 ... Initial Data Shows 100% Disease Control in 5 Out of 5 Patients With Recurrent Glioblastoma With Two Patients in Near Complete Response Treated ...

4. cancernetwork.com cancernetwork.com/view/ttfields-plus-temozolomide-pembrolizumab-controls-tumors-in-glioblastoma

TTFields Plus Temozolomide/Pembrolizumab Controls ... Patients with newly diagnosed glioblastoma had improved survival when treated with TTFields plus temozolomide and pembrolizumab.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06556563

EF-41/KEYNOTE D58: Phase 3 Study of Optune ... This is a multicenter, two-arm, randomized, double-blind, placebo-controlled study of Optune® (Tumor Treating Fields at 200 kHz) together with maintenance ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23560574/

Results of the NeuroBlate System first-in-humans ... - PubMed The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

7. journals.lww.com journals.lww.com/neurosurgery/fulltext/2020/09000/laser_ablation_of_abnormal_neurological_tissue.40.aspx

Laser Ablation of Abnormal Neurological Tissue Using... Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation.

8. neuroblatemeded.com neuroblatemeded.com/resources/12-month-outcomes-for-patients-receiving-minimally-invasive-laser-ablation/

12-Month Outcomes for Patients Receiving Minimally Invasive ... Summary. Discussion of 12-month outcomes for brain tumor patients receiving minimally invasive laser ablation. Highlights/Chapters.

9. thejns.org thejns.org/view/journals/j-neurosurg/118/6/article-p1202.xml

Results of the NeuroBlate System first-in-humans Phase I ... The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303846720302857

Survival outcomes in patients with recurrent glioblastoma ... The most common complications were seizures (2%), motor deficits (1.5 %), wound infection (1.5 %), transient hemiparesis (1%) and hemorrhage (0.5 %). No deaths ...