TTFields + Pembrolizumab for Lung Cancer

(KEYNOTE B36 Trial)

Recruiting at 24 trial locations

Overseen By Kassie Balestrieri, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NovoCure GmbH

Must be taking: Pembrolizumab

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: CNS metastases, EGFR mutation, ALK translocation, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating advanced or metastatic non-small cell lung cancer (NSCLC) that is PD-L1 positive. It combines an experimental treatment called Tumor Treating Fields (TTFields), which uses electric fields to target cancer cells, with the known drug pembrolizumab. The goal is to determine if TTFields with pembrolizumab helps patients live longer without their cancer worsening, compared to using pembrolizumab alone. Individuals diagnosed with advanced NSCLC, who have not received previous treatments for it and can use the TTFields device, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot receive other systemic or localized cancer treatments while participating.

What prior data suggests that the NovoTTF-200T device is safe for treating lung cancer?

Research has shown that using Tumor Treating Fields (TTFields) with the NovoTTF-200T device, alongside pembrolizumab, appears safe. Patients have generally tolerated this treatment well. In studies, most side effects were mild to moderate, such as skin irritation at the device site and fatigue.

Pembrolizumab is already approved for other uses and has a known safety record. Common side effects include tiredness, skin rash, and nausea, while serious side effects are less common but possible.

Overall, combining TTFields and pembrolizumab has not revealed any unexpected safety issues. Prospective trial participants should discuss potential side effects with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lung cancer, which often include chemotherapy and targeted therapies, the combination of TTFields and pembrolizumab is unique because it employs a novel mechanism of action. TTFields, or Tumor Treating Fields, use electric fields to disrupt cancer cell division, which is quite different from traditional approaches. Meanwhile, pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. By combining these two methods, researchers are hopeful that this approach could enhance the effectiveness of lung cancer treatment, offering a dual attack on the tumor that could lead to improved outcomes for patients.

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

Research shows that using Tumor Treating Fields (TTFields) with pembrolizumab may help treat non-small cell lung cancer (NSCLC). In this trial, one group of participants will receive the combination of TTFields and pembrolizumab. Studies have found that this combination can help the immune system better recognize and fight the cancer. Specifically, it has significantly extended progression-free survival, the period during which the cancer does not worsen, in previous patients. Other trials suggest that this combination might be more effective than pembrolizumab alone, which is being tested in the control group of this trial. These findings support the potential effectiveness of this treatment for patients with advanced NSCLC. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 22 or older with advanced or metastatic non-small cell lung cancer (NSCLC) that hasn't been treated before. Participants must have a PD-L1 positive tumor and be able to use the NovoTTF-200T device. They should not have certain genetic mutations, untreated brain metastases, or recent major surgery, and cannot be pregnant.

Inclusion Criteria

Your disease can be measured using a standard method called RECIST 1.1.

My lung cancer is advanced and cannot be removed by surgery, and it does not have certain genetic changes.

I have not had any drug treatments for my lung cancer.

Exclusion Criteria

My condition can be treated with surgery or chemoradiation aiming for a cure.

I have had treatment for advanced lung cancer before, but not palliative radiotherapy.

I will not need any cancer treatment other than the study's while participating.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive TTFields to the thorax using the NovoTTF-200T device for an average of 18 hours a day concomitant with pembrolizumab 200 mg IV every 3 weeks, or pembrolizumab alone

24 months

Follow-up

Participants are monitored for disease status monthly by telephone until disease progression, initiation of non-study cancer treatment, consent withdrawal, or end of study

What Are the Treatments Tested in This Trial?

Interventions

• NovoTTF-200T

Trial Overview The study tests Tumor Treating Fields (TTFields) delivered by the NovoTTF-200T alongside pembrolizumab versus pembrolizumab alone in treating NSCLC. It aims to see if adding TTFields improves progression-free survival compared to just the drug treatment.

How Is the Trial Designed?

Group I: Arm 2: Control Group Experimental Treatment 1 Intervention

Pembrolizumab (MK-3475)

Group II: Arm 1: Treatment Group Experimental Treatment 2 Interventions

Pembrolizumab (MK-3475) and TTFields

NovoTTF-200T is already approved in United States, European Union, Japan for the following indications:

Approved in United States as NovoTTF-200T for:

• Glioblastoma multiforme

Approved in European Union as NovoTTF-200T for:

• Glioblastoma multiforme

Approved in Japan as NovoTTF-200T for:

• Glioblastoma multiforme

Who Is Running the Clinical Trial?

NovoCure GmbH

Lead Sponsor

Trials

16

Recruited

3,700+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Immune checkpoint inhibitors, like pembrolizumab, have shown significant and lasting improvements in treating advanced non-small cell lung cancer (NSCLC), particularly in patients with high PD-L1 expression.

Pembrolizumab has been approved by the U.S. FDA for NSCLC that has progressed after other treatments, indicating its efficacy in a challenging patient population, but further research is needed to enhance treatment outcomes through combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of pembrolizumab in the treatment of advanced non-small cell lung cancer. Santabarbara, G., Maione, P., Rossi, A., et al.[2021]

In a review of five randomized trials with nearly 2,000 participants, both pembrolizumab (PEM) and tislelizumab (TIS) combined with chemotherapy showed significant improvements in progression-free survival (PFS) compared to chemotherapy alone, with median PFS of 8.89 months for PEM and 7.97 months for TIS.

The indirect comparison indicated that PEM and TIS have similar efficacy when combined with chemotherapy, meeting regulatory criteria for equivalence, suggesting that either treatment could be a viable option for patients with advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab plus chemotherapy vs. pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. Messori, A., Rivano, M., Chiumente, M., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

Immunotherapy has significantly improved survival rates for patients with metastatic non-small cell lung cancer (NSCLC), particularly in stage IV cases, with some patients experiencing durable responses.

Immune checkpoint inhibitors like nivolumab and atezolizumab are effective treatment options regardless of PD-L1 expression, while pembrolizumab requires a minimum level of PD-L1 expression to be used, highlighting the importance of biomarker testing in treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in previously treated non-small cell lung cancer (NSCLC). Leal, TA., Ramalingam, SS.[2020]

In a study of 256 patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression, pembrolizumab (P) alone showed a median overall survival (OS) of 12.5 months, while the combination of pembrolizumab with platinum-based chemotherapy (PCT) had a median OS of 20.4 months, suggesting a potential advantage for PCT, especially in female patients.

Despite the observed differences in OS, the study found no statistically significant differences in long-term outcomes between P and PCT, indicating that further randomized trials are needed to confirm these findings and explore efficacy across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a monotherapy or in combination with platinum-based chemotherapy in advanced non-small cell lung cancer with PD-L1 tumor proportion score (TPS) ≥50%: real-world data. Dudnik, E., Moskovitz, M., Rottenberg, Y., et al.[2022]

In a phase 3 trial involving 616 patients with untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC), the addition of pembrolizumab to standard chemotherapy significantly improved overall survival, with a 12-month survival rate of 69.2% compared to 49.4% for the placebo group.

Patients receiving pembrolizumab also experienced longer progression-free survival (8.8 months) compared to those on placebo (4.9 months), demonstrating the efficacy of pembrolizumab in enhancing treatment outcomes for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., et al.[2022]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

In a study of 187 patients with non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, those with PD-L1 levels of 90%-100% showed significantly better treatment outcomes with pembrolizumab, including a higher overall response rate (60% vs. 32.7%) and longer median progression-free survival (14.5 months vs. 4.1 months).

Patients with higher PD-L1 expression not only had improved response rates but also longer overall survival, indicating that PD-L1 levels can be a critical factor in predicting the efficacy of pembrolizumab as a first-line treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Aguilar, EJ., Ricciuti, B., Gainor, JF., et al.[2023]

Immune checkpoint inhibitors, such as Pembrolizumab, Nivolumab, and Atezolizumab, have significantly improved treatment outcomes for advanced nonsmall cell lung cancer (NSCLC), especially for patients who have progressed after chemotherapy.

A new patient-oriented algorithm has been developed to help clinicians choose the most effective and personalized treatment options for advanced NSCLC, aiming to enhance patient quality of life and survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current uses of check inhibitors in the fight against advanced and/or metastatic lung cancer: will immunotherapy overcome chemotherapy? Cetin, B., Bilgetekin, İ., Ozet, A.[2020]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

In a study of 97 non-small cell lung cancer patients treated with pembrolizumab, 40% experienced treatment-related adverse events (trAEs), with common ones being rash, fatigue, and hypothyroidism.

Patients who experienced trAEs had significantly better clinical outcomes, including a higher objective response rate (38.5% vs. 8.9%), longer progression-free survival (248 days vs. 60 days), and longer overall survival (493 days vs. 144.5 days), suggesting that trAEs may be indicative of a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Lisberg, A., Tucker, DA., Goldman, JW., et al.[2022]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06558799?term=NCT06558799&rank=1

NCT06558799 | LUNAR-4: Effect of Tumor Treating Fields ... The purpose of the study is to test the effectiveness and safety of TTFields therapy, delivered using the NovoTTF-200T device, concomitant with pembrolizumab in ...

2. 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)

3. novocuretrials.com novocuretrials.com/cancer-clinical-trials/lung-cancer-clinical-trials-keynote-b36

KEYNOTE B36 - Lung Cancer Clinical Trial The KEYNOTE B36 study is pilot, randomized, open-label study designed to evaluate the safety and effectiveness of TTFields, generated by the medical device ...

4. novocure.com novocure.com/novocure-announces-presentations-tumor-treating-fields-therapy-including-new-clinical-data-and-real

Novocure Announces Presentations on Tumor Treating ... an oral presentation of data from the 2-THE-TOP trial, suggesting TTFields therapy had an enhanced effect with pembrolizumab in patients with newly diagnosed ...

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

Article 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04892472

Study Details | NCT04892472 | EF-36/Keynote B36: A Pilot, ... This is a multicenter, randomized, open-label study of Tumor Treating Fields (TTFields) at 150 kHz to the thorax using the NovoTTF-200T System with IV ...