Dr. Uri Weinberg Explains Novel Mesothelioma Treatment NovoTTF-100L

NovoTTF-100L for mesothelioma

In May 2019, the Federal Drug Administration (FDA) approved a new mesothelioma treatment for the first time in 15 years. The new treatment, known as NovoTTF-100L, is applied in combination with chemotherapy. The combination treatment was approved as a first-line therapy for patients with pleural mesothelioma. The approval came following positive results from the STELLAR study, which showed a median overall survival of 18.2 months.

Novocure is the oncology company that developed NovoTTF-100L, a treatment based on tumor treating fields (TTFields). recently spoke with Novocure’s VP of Clinical Development, Dr. Uri Weinberg, to learn more about the novel treatment and its potential in future research.

Tumor Treating Fields for Mesothelioma

Dr. Weinberg has worked at Novocure since 2008. As a medical student, he met Yoram Palti, a professor emeritus of physiology and biophysics, who invented tumor treating fields (electrical fields that disrupt cell division). Palti later founded Novocure and invited Dr. Weinberg to work with the company. Novocure was a startup at the time, focused on developing a novel treatment for cancer.

“This was very, very attractive to me as a young physician,” Dr. Weinberg recalled. “This was a way for me to make a real difference in the lives of patients and their families.”

Today, the company has grown to nearly 800 employees. Since its founding, Dr. Weinberg and his colleagues have been testing tumor treating fields as a cancer treatment, initially focusing on glioblastoma, a type of aggressive brain tumor. In recent years, they decided to investigate TTFields for other cancers, including mesothelioma.

“The disease is very interesting and poses a true challenge to researchers, and there is a real unmet need for novel therapies,” Dr. Weinberg said of his interest in researching mesothelioma. “In preclinical experiments conducted by our research team at Novocure, we saw that mesothelioma cells are especially susceptible to tumor treating fields, which cause cellular death when applied to such tumor models.”

Tumor treating fields work by applying non-invasive, low-intensity alternating electrical fields to disrupt cell division. The fields interfere with the normal function of proteins that allow for cell division, thus stopping or slowing cancer growth.

Currently, the treatment is only approved as a first-line therapy in combination with chemotherapy. More research is needed to understand the efficacy of NovoTTF-100L when combined with other treatments or as a second-line option for patients.

“From the abundance of data we have regarding their mechanism of action, I certainly think TTFields could potentially be effective in other stages of disease, such as following recurrence. This has not been tested in clinical trials so far,” Dr. Weinberg explained. “In glioblastoma, we know that starting TTFields treatment sooner, in order to have a longer duration of treatment, can result in better outcomes. Starting TTFields at an earlier stage of mesothelioma, rather than at a later stage, could be potentially more effective for patients. We therefore designed the clinical trial in mesothelioma for first line.”

Though NovoTTF-100L has only been tested with chemotherapy so far, Dr. Weinberg can see the potential of tumor treating fields with other therapies, such as immunotherapy.

“Being a low toxicity therapy, there is an opportunity to combine TTFields with other treatments that are used to treat malignancies like mesothelioma. The treatment is applied locally, so it is not expected to affect the distant body systems. The most common adverse event associated with the device is skin irritation, but this is usually reported as a mild effect by the treating doctors,” Dr. Weinberg said.

“So, based on preclinical data from animal models that were tested, the combination of TTFields with immune checkpoint inhibitors could potentially be effective.” He continued, “This has been shown in other cancer models, but we might see the same results in mesothelioma. We think that our results suggest a stronger immune response against the cancer, so there’s the opportunity to see a greater efficacy when the two treatments are combined. But to draw definitive conclusions regarding the effects of TTFields with immune checkpoint inhibitors in patients, we will need to see results of clinical studies.”

The Future of Tumor Treating Fields

Developing the first FDA-approved mesothelioma treatment in 15 years was an exciting moment for Dr. Weinberg and the rest of the team at Novocure.

“It involves a lot of emotions. Obviously, being part of the team that investigated tumor treating fields in mesothelioma — leading to the approval of the FDA following so many years without new treatments approved — it makes me feel very happy and proud.”

Dr. Weinberg continued, “There are numerous people that dedicated so much of their time and efforts to reach this moment. From the inventor Professor Palti, the preclinical, physics and clinical research teams, as well as Novocure’s management and our CEO, Mr. Asaf Danziger. In order for such a thing to be successful, all of these people and many others need to be engaged in tremendous work and collaborate with each other. It took so many years to develop from the initial idea to get this to patients. Obviously, this would have never happened without the dedication of the clinicians who conducted the clinical trial, the patients themselves and their family members. I am grateful for their sacrifice.”

Overall, Dr. Weinberg and his colleagues at Novocure are excited to see this treatment help mesothelioma patients.

“The most rewarding feeling to everybody, and to me personally, is that mesothelioma patients now have another treatment option after so much time. We hope this makes a real difference for people who suffer so much from this disease.”

Though the team currently has no active clinical trials for mesothelioma, TTFields continue to be studied in other cancers. Other trials are investigating TTFields in phase III trials for non-small cell lung cancer, brain metastases, pancreatic cancer and ovarian cancer. Smaller pilot studies are currently being done in hepatocellular cancer and will soon be done in gastric cancer. The team at Novocure is also preparing for future clinical trials.

“We continue to research glioblastoma, the other cancer where we received FDA approvals. We continue to research this indication with a large phase III trial for newly diagnosed glioblastoma,” Dr. Weinberg said. “We are preparing more future clinical studies for new malignancies. We have a very significant pipeline of cancer models that have been tested pre-clinically and successfully with TTFields, so the number of cancers tested in clinical studies is expected to increase over time.”

Dr. Weinberg hopes NovoTTF-100L will become more widely available across the world and for more types of cancer.

“First and foremost, I’m very hopeful that this treatment is available in the U.S. for patients now and in other regions around the world. We hope to make a real difference in the lives of patients and to allow patients to get better therapy and outcomes. So that’s the most important, in my view,” Dr. Weinberg stated.

“We feel tumor treating fields is a platform technology that should be tested in different countries and hopefully demonstrate efficacy in different tumor types,” He continued. “The goal of Novocure is to extend survival in some of the most aggressive forms of different cancers. We will do whatever we can to achieve that, and I am committed to this myself.”