NovoTTF-200A + Pembrolizumab for Melanoma

Not yet recruiting at 1 trial location

Overseen By Eric T Wong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eric Wong, MD

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Chemotherapy, Radiotherapy, Autoimmune, others

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

Compensation: Varies

Number of Visits: 69

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat melanoma that has spread to the brain by using the NovoTTF-200A device, combined with the drug pembrolizumab, to assess their safety and effectiveness together. The goal is to determine if this combination can manage melanoma specifically in the brain. Individuals with brain-metastasized melanoma who have had issues with or cannot take certain therapies might be suitable for this trial. Participants must be prepared to use the NovoTTF-200A device regularly and have caregiver support for device management. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy or radiotherapy within 4 weeks before the trial or if you are on systemic steroid therapy at a dose equivalent to 4 mg daily of dexamethasone or more within 7 days prior to the trial.

What prior data suggests that the NovoTTF-200A device is safe for treating melanoma with brain metastases?

Research shows that using the NovoTTF-200A device with the drug pembrolizumab may help treat cancer, but ensuring safety is crucial. Previous studies have examined pembrolizumab in people with melanoma, and the results suggest it is generally safe. While side effects can occur, they are usually manageable.

NovoTTF-200A, a device used to treat tumors, has been tested with pembrolizumab. Studies indicate that this combination can help the body fight tumors more effectively. Safety data from these studies suggest that both treatments are generally safe together. However, some patients might experience side effects like tiredness or skin reactions.

Although research is ongoing, early results are promising. Researchers are closely monitoring the combination treatment to ensure it is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NovoTTF-200A combined with Pembrolizumab for melanoma because it offers a unique approach compared to traditional treatments like surgery, radiation, and chemotherapy. NovoTTF-200A uses electric fields to disrupt cancer cell division, a novel mechanism that differs from the usual immune checkpoint inhibitors or targeted therapies. Combined with Pembrolizumab, a well-known immune checkpoint inhibitor that helps the immune system attack cancer cells, this treatment has the potential to enhance effectiveness by targeting cancer on multiple fronts. This dual approach could offer an innovative way to manage melanoma and improve outcomes for patients.

What evidence suggests that the NovoTTF-200A device is effective for treating metastatic melanoma in the brain?

Research has shown that pembrolizumab, a medicine that helps the immune system fight cancer, improves survival rates in people with advanced melanoma. Data from ten years of study reveal that 34% of patients treated with pembrolizumab were still alive, indicating a significant survival benefit. Early research suggests that NovoTTF-200A might help treat melanoma that has spread to the brain by using electric fields to stop cancer cells from dividing. Although less information exists on NovoTTF-200A alone, this trial will study the combination of NovoTTF-200A with pembrolizumab, which shows promise for better effectiveness in treating melanoma that has spread to the brain. This combination aims to leverage pembrolizumab's proven success and NovoTTF-200A's novel approach for potentially better outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Eric Wong, MD

Principal Investigator

Lifespan Cancer Institute

Are You a Good Fit for This Trial?

Adults with melanoma that has spread to the brain can join this trial. They need measurable disease, a life expectancy over 6 months, and normal organ/marrow function. Participants must be willing to use birth control and have support for device treatment. Excluded are those recently on certain therapies, with hypersensitivities or other cancers, serious health issues like heart conditions or infections, pregnant/breastfeeding women, or uncontrolled illnesses.

Inclusion Criteria

My organs and bone marrow are functioning normally.

You are expected to live for more than 6 months.

I have taken a pregnancy test in the last 14 days and it was negative.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

Participants who are receiving any other investigational agents

I have been treated for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive NovoTTF-200A continuously and Pembrolizumab every 3 weeks in a 3+3 design cohort

21 days per cycle

Continuous device use, Pembrolizumab every 3 weeks

Phase II Treatment

Participants continue to receive NovoTTF-200A continuously and Pembrolizumab every 3 weeks

21 days per cycle

Continuous device use, Pembrolizumab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Visits at 63, 129, 189 days, and 30 days after last treatment

What Are the Treatments Tested in This Trial?

Interventions

• NovoTTF-200A
• Pembrolizumab

Trial Overview The study is testing NovoTTF-200A (a device) combined with Pembrolizumab (a drug) for safety and effectiveness in treating brain metastases from melanoma. The goal is to see how well these treatments work together against this advanced stage of skin cancer.

How Is the Trial Designed?

Group I: PHASE 2: NovoTTF-200A + PEMBROLIZUMAB Experimental Treatment 2 Interventions

* NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Group II: PHASE 1: NovoTTF-200A + PEMBROLIZUMAB Experimental Treatment 2 Interventions

The Phase I portion of the study will have a 3 + 3 design and consist of one cohort treated * NovoTTF-200A will be applied continuously, with 21 consecutive days defined as a treatment cycle. * Pembrolizumab will be administered once every 3 weeks, with 21 consecutive days also defined as a treatment cycle

Who Is Running the Clinical Trial?

Eric Wong, MD

Lead Sponsor

Trials

1

Recruited

30+

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Published Research Related to This Trial

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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 study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02130466

NCT02130466 | A Study of the Safety and Efficacy ... A Study of the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With Trametinib and Dabrafenib in Participants With Advanced Melanoma (MK-3475 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11674442/

Immune Checkpoint Inhibitors in Glioblastoma IDHwt Treatment Expanded Access for Pembrolizumab (MK-3475) to Patients with Melanoma or Glioblastoma/Glioma After Failed Standart Therapy, at High ...

3. withpower.com withpower.com/trial/phase-2-neoplasms-second-primary-10-2019-31ac1

NovoTTF-200A + Pembrolizumab for Melanoma What data supports the effectiveness of the drug pembrolizumab for treating melanoma? Pembrolizumab has been shown to improve survival and response rates in ...

4. ctv.veeva.com ctv.veeva.com/study/novottf-200a-pembrolizumab-in-melanoma-brain-metastasis

NovoTTF-200A + Pembrolizumab In Melanoma Brain Metastasis The purpose of this study is to obtain information on the safety and effectiveness of the study device, NovoTTF-200A, in melanoma participants ...

5. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02973789

NCT02973789 | Effect of Tumor Treating Fields (TTFields) ... The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-200T device, concurrent ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8665

LUNAR-2: Pivotal, randomized, open-label study of tumor ... A pivotal, global, randomized, trial investigating the efficacy and safety of TTFields concomitant with pembrolizumab (P) and platinum-based chemotherapy (C)

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6094659/

Pembrolizumab in the management of metastatic melanoma Improved overall survival was demonstrated in both treated and untreated melanoma patients in two key studies representing a breakthrough in this field [23,24].

10. 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 ...