Tumor Treating Fields Creator on Mesothelioma Therapy

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In 2019, Tumor Treating Fields became the second therapy approved by the U.S. Food and Drug Administration for treatment of malignant pleural mesothelioma.

It has been 15 years since the FDA first approved the chemotherapy regimen of pemetrexed (Alimta) with platinum therapy as the only standard option for patients.

The road to this new mesothelioma treatment has seen the completion of several successful clinical trials and an innovative method of collecting research data from many sources. The path ahead promises advancements and improvements to this therapy and the possibility of improved survival for patients with advanced disease.

Novocure’s chief science officer and one of the co-creators of Optune Lua Tumor Treating Fields, Dr. Uri Weinberg, recently discussed the history of its development with The Mesothelioma Center at Asbestos.com.

He also detailed the ongoing progress of widening its availability to patients and the work his team is doing to expand the therapeutic uses of TTFields.

“When I joined Novocure 12 years ago, I wanted to do something that would be the most impactful for patients and their families,” Weinberg said. “That was what drove me to study medicine.”

STELLAR Results Led to TTFields Development

The clinical trial STELLAR produced the results that would lead to the device’s approval by the FDA in 2019.

“The STELLAR study was designed as a single-arm trial for 80 unresectable pleural mesothelioma patients who all received Alimta and platinum agent concomitant with TTFields at 150kHz as first-line therapy,” Weinberg said. “The study was designed to be compared to historical control studies, and the results demonstrated that the median overall survival for these patients treated with TTFields in addition to their chemotherapy was 18.2 months.”

The study demonstrated impressive results that improved overall survival for mesothelioma patients.

“All patients were treated with the Optune Lua device, and overall survival was 21.2 months for patients with epithelioid type and 12.1 months for patients with a non-epithelioid type [about 25% of patients],” said Weinberg. “We had 40% of patients who had a partial response, and median progression-free survival was 7.6 months. STELLAR demonstrated that Optune Lua could be combined with chemotherapy with no increase in serious adverse events when added to the standard of care.”

New Trials Include Collaboration with Merck Using Keytruda

Tumor Treating Fields works by delivering alternating electrical fields that disrupt the natural process of cell division, called mitosis. Engineers tune the electrical fields to a specific frequency to affect mitosis mechanisms, which are ubiquitous to all types of cancer cells.

Doctors prescribe the device with chemotherapy in a multimodal therapy plan.

“Currently, we are already testing TTFields in several clinical trials,” Weinberg said. “We have ongoing phase III trials in pancreatic adenocarcinoma, non-small cell lung cancer, ovarian carcinoma and brain metastasis from small cell lung cancer. We are also running early phase trials in hepatocellular [liver] and gastric cancer.”

Novocure recently announced a collaboration with the pharmaceutical company Merck to test TTFields with the immunotherapy agent pembrolizumab (Keytruda). Keytruda is an anti-PD-1 immune checkpoint inhibitor that activates the patient’s immune system to fight cancer cells.

The new study will open within a few months to patients with advanced or metastatic non-small cell lung cancer.

“This study takes into account the very encouraging preclinical results we have seen in animal models,” Weinberg said. “It demonstrates that TTFields could actually increase the level of inflammation and response of the immune system against the tumor cells when combined with immune checkpoint inhibitors.”

Novocure Works to Increase TTFields Availability

Treatment centers in 49 locations across the U.S. have gone through training and certification to prescribe TTFields for mesothelioma, but adoption hasn’t been as swift as with other treatments.

“When looking at the history of medicine, one needs to consider that the world of medicine, for very clear reasons, needs to be a little conservative and a little bit careful when it comes to the introduction of new technology,” Weinberg said.

“Novocure’s strategy has been to invest a lot in the science of preclinical research,” he added. “For over two decades, we have been working on establishing the very solid science in order to now use it with the health care providers in order to educate them, make them feel comfortable with our mechanism of action and with our clinical data.”

Novocure has reported a consistent increase in the number of patients receiving the device since its release. According to Weinberg, part of Novocure’s strategy for adoption is thoroughly educating mesothelioma treatment centers and their health care providers.

“We are utilizing scientific publications available in the literature, both preclinical and clinical, which is a major part of what is incorporated into all our training,” he said.

Throughout the COVID-19 pandemic, Novocure’s field teams have ensured that the ongoing research is not compromised.

“The important thing for us in Novocure’s philosophy is that we can maintain the quality of our work,” Weinberg said. “We insist on doing things with the right measures and levels of accuracy, even though we have to change the mode of action.”

Future TTFields Updates to Bring More Flexibility

Due to the current nature of Tumor Treating Fields as a home device that patients can carry with them, there are few restrictions with the treatment. Patients can maintain a high quality of life while using the device in most environments.

“We know that patients can maintain their daily activities, socializing with friends and going out, and traveling, cycling, mountain climbing and skiing,” Weinberg said. “This is extremely rewarding to our entire team, as our approach has always been to do whatever we can to make treatment easier for patients and maintain their quality of life.”

Weinberg cautions that patients on TTFields should always discuss with their physician which activities are safe for their condition while on the therapy.

“This is what our engineering team continuously is working on, making the device more convenient,” he said. “We’re investing a lot in this.”

Novocure is working on updates to the Optune Lua device that will hopefully improve its effectiveness against more types of cancer.

“One such study that is already ongoing is our trial where we use high-intensity arrays,” Weinberg said. “We increase the surface of the arrays to deliver higher currents without reaching the threshold of temperature at which the increase in current is outed.”

The Optune Lua team is also utilizing MRI data to map certain cancers and personalize array placement on the patient’s body. According to Weinberg, updates to the software are in progress.

“Our goal is to have one software package used by the physician to facilitate the planning of the TTFields treatment for each tumor,” he said.

Novocure has only reached “the tip of the iceberg” with the possibilities of Tumor Treating Fields, Weinberg said. As availability of the device expands for patients, many physicians hope it will improve the prognosis for this rare and deadly disease. Currently there is no mesothelioma cure.

“What we hear from physicians now is that this is going on very well,” Weinberg said. “The general feedback I’m getting is that patients who apply for Optune Lua and use the device are pleased with the treatment and the opportunity.”

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Sean Marchese, MS, RN, author for The Mesothelioma Center

Oncology Medical Writer and Registered Nurse

Sean Marchese is a registered nurse and medical writer at The Mesothelioma Center. He has a background in respiratory and thoracic oncology clinical trials. Sean has assisted physicians with the development of chemotherapy and surgical planning for patients with head, neck and thoracic cancers. As a registered nurse, Sean has worked with cancer patients undergoing pain management therapies and patients with brain and nervous system cancers in an inpatient setting.

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