LUNAR-4

The LUNAR-4 Study is intended for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (TPS ≥1%) and who have received prior PD-1/PD-L1 inhibitor and platinum-based chemotherapy. This clinical study is evaluating the safety and efficacy of Tumor Treating Fields (TTFields), delivered by the NovoTTF-200T device, together with immunotherapy, pembrolizumab.

Novocure GmbH, the study sponsor, maintains this website to help patients get basic information about the study.

If you want to take part in the LUNAR-4 Study, please contact one of the participating centers as soon as possible.

Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division. TTFields may interfere with the electrically charged cellular components of cancer cells, disrupting their normal function and ultimately may lead to cell death. As a result, the cancer cell division may be slowed, or even stopped, inhibiting tumor growth. Additionally, laboratory experiments suggest TTFields have the ability to enhance how the body’s immune system reacts to the tumor, which may make it more difficult for cancer cells to repair DNA damage and interfere with cancer cells ability to migrate to different regions of the body.

TTFields are delivered to the body region where the primary tumor is located using an investigational medical device called NovoTTF-200T. NovoTTF-200T is a portable, battery-operated device designed to deliver TTFields of 150kHz.

Patients receiving TTFields need to wear four adhesive patches called transducer arrays (arrays) on their chest, which deliver the TTFields non-invasively to the cancer site. The device is intended for continuous home use by patients.

NovoTTF-200T for the treatment of non-small cell lung cancer is investigational; it has not been approved by health authorities for this indication. The safety and effectiveness of TTFields in this condition is still unknown, and will be evaluated in this clinical study.

TTFields therapy has been approved for adult patients with recurrent (as a monotherapy) and newly diagnosed glioblastoma (GBM) (together with a chemotherapy called temozolomide), in the United States under the Premarket Approval (PMA) pathway. It has obtained a CE mark in Europe, and is approved in Japan for the same indication. The use of TTFields together with chemotherapy has also been CE marked in Europe and approved for adult patients with malignant pleural mesothelioma (MPM) under the FDA’s Humanitarian Device Exemption (HDE) pathway in the United States.

The LUNAR-4 Study is a pilot, single-arm, open-label, multinational study designed to evaluate the safety and efficacy of Tumor Treating Fields (TTFields, 150 kHz), generated by the medical device NovoTTF-200T, together with pembrolizumab for the treatment of metastatic non-small cell lung cancer (NSCLC) previously treated with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy. Study patients will receive continuous TTFields treatment, delivered by the NovoTTF-200T device, together with pembrolizumab, which is delivered intravenously. The study is expected to enroll 69 patients in multiple medical centers around the world.

The study is intended for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (TPS ≥1%) and who have received prior PD-1/PD-L1 inhibitor and platinum-based chemotherapy.

Final eligibility can only be determined by a clinical study physician at one of the participating clinical study centers.

Patients enrolled in this study will receive continuous TTFields treatment, delivered by the NovoTTF-200T device, together with pembrolizumab, which is delivered intravenously. TTFields treatment will be continuous for at least 18 hours a day on average.

TTFields treatment may be continued until disease progression as assessed by the investigator, or until any of the treatment discontinuation conditions are met.

To receive treatment, the patient needs to wear four adhesive patches called arrays on their chest which deliver the TTFields non-invasively to the tumor location. Array placement may require shaving of the contact site before starting to use the device, and twice a week for as long as its use continues. The arrays are replaced and re-applied on a regular basis for as long as the patient is receiving the treatment.

The use of NovoTTF-200T will include training on the operation of the equipment by a qualified Device Support Specialist (DSS). Patients will continue to use the device at home.

Once trained, patients using NovoTTF-200T can setup and use the device themselves (with the help of a family member or a caregiver if needed), or may receive support from their DSS.

The device is designed to be user-friendly and all technical aspects related to using it are maintained by the DSS. The DSS can also help patients in finding technical solutions to allow each individual to receive TTFields while maintaining his/her normal daily routines.

For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with a LUNAR-4 study physician:

Inclusion Criteria (summary, not complete list)

1. At least 22 years of age in the USA or at least 18 years of age outside of the USA.
2. Life expectancy of > 3 months.
3. Histologically or cytologically confirmed diagnosis of NSCLC.
4. Documented positive tumor PD-L1 expression (TPS≥1%).
5. ECOG Score of 0-1.
6. Diagnosis of radiological progression while on or after first platinum-based systemic therapy administered for advanced or metastatic disease.
7. Subjects must have received one line of PD-1/PD-L1 inhibitor therapy for advanced or metastatic NSCLC.
8. Subjects who received PD-1/PD-L1 inhibitor for advanced disease, must have had a best response on PD-1/PD-L1 inhibitor of stable disease, partial response or complete response (in the opinion of the treating physician).

Exclusion Criteria (summary, not complete list)

1. Mixed small cell and NSCLC histology.
2. Subject must not have leptomeningeal disease or spinal cord compression.
3. Contra-indication for PD-1/PD-L1 inhibitor therapy.
4. Subject with more than (>) 2 lines of therapy in the advanced setting.
5. Subject had major surgery <3 weeks prior to study enrollment.
6. Subject received lung radiation therapy of > 30 Gy within 6 months before the first dose of study treatment.
7. Subject has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Subject has active autoimmune disease that has required systemic treatment in past 2 years.
9. Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study enrollment.
10. Significant comorbidity which is expected to affect the subject’s prognosis or ability to receive the study treatment.
11. Subject must not be receiving or planning to receive another investigational therapy during study participation.
12. Implanted electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso.

Expected total enrollment is 69 patients. The study will enroll patients in multiple medical centers around the world. Please contact a center near you as soon as possible if you would like to learn more about participating in the LUNAR-4 study.

There will be no cost to participate in this study. The study sponsor (Novocure) will pay for reasonable treatment related supplies, including the NovoTTF-200T device and accessories. Patients and their insurance will be responsible for medical treatments received in the normal course of patient care. The study sponsor may also reimburse patients for reasonable travel costs directly related to the study’s procedures. Such reimbursements may be done according to the policy of the study center at which the patient is being treated and according to the applicable country regulations. Prior to enrolling in the study, please consult with the clinical study team at the center about the local reimbursement policy, and your rights.

Patients participating in the LUNAR-4 Study should use the device continuously for an average of at least 18 hours a day, but may take breaks during daily use for some activities. The treating physician may modify the treatment schedule and use of the device as needed.

The DSS will provide device support to patients and caregivers.

Please note: While the DSS provides comprehensive device and technical support, they do not offer medical advice. Please direct all medical questions to your study clinician.

NovoTTF-200T is intended for continuous use for at least 18 hours a day. The device does not interfere with household or personal electrical devices. There is no exposure of TTFields to non-users, such as co-workers and family members.

NovoTTF-200T is a wearable, portable device. Use of the device requires shaving of the contact site and the application of adhesive patches called arrays to the chest. Naturally, some patients may be concerned about their appearance or their lifestyle while using the device. The arrays and the wires connecting to the device may be concealed underneath the patient’s clothes. By doing so, the bag carrying the device may be the only element of NovoTTF-200T visible to others. The medical team and DSS will provide personalized assistance specific to each patient on how best to wear the device.

In addition to regularly shaving the contact area, patients will regularly change their arrays to ensure continuous treatment. The medical team will assist in creating a plan and instructing patients on array placement.

The device is designed to give patients the option to maintain their lifestyle without interference to their daily routines. Patients can consult the treating physician ahead of time regarding any activity in question. In addition, the DSS can provide information to address any lifestyle concerns.

The device bag can be worn as a shoulder bag, a backpack, a messenger bag, or hand-held. The total weight of the device including a battery is around 1.3 kilograms, or 2.7 pounds. Novocure can provide as many portable batteries as needed.

In order to ensure continuous treatment, patients will plug NovoTTF-200T in to an AC adapter when staying in a location for more than a few hours.

Cancer cells divide and multiply rapidly within the lung cancer tumor. These cancer cells carry different types of electrically charged elements that play a role during the cell division process. Other healthy cells in the chest multiply at a much slower rate, if at all.

The NovoTTF-200T device in this study delivers low-intensity, wave-like electric fields to the location of the tumor. These fields are known as Tumor Treating Fields (TTFields).

Preclinical studies showed that due to the shape and size of cancer cells when they are multiplying, TTFields cause electrically-charged cellular components of these cells to change their location within the dividing cell, disrupting their normal function and may ultimately lead to cell death.

In addition, cancer cells also contain miniature building blocks that act as tiny motors in moving essential parts of the cells from place-to-place. TTFields interfere with the normal orientation of these tiny motors since they are also electrically charged. As a result, the cancer cell division is slowed, or even stopped, inhibiting tumor growth.

A summary of TTFields’ mechanism of action is illustrated in the following animation:

To date, the sponsor has investigated a number of similar devices developed to deliver TTFields to different tumors. The main difference between the previously studied devices and NovoTTF-200T is the frequency of TTFields provided by each device. The frequency is adjusted by the manufacturer of the devices in order to optimize the treatment for each treated cancer, based on data from laboratory experiments.

NovoTTF-100L, a previous model of NovoTTF-200T, has been evaluated in a pilot study of 42 patients with inoperable non-small cell lung cancer (NSCLC) patients who received TTFields together with standard chemotherapy to evaluate the safety of TTFields in this indication. A follow up phase 3 study including both the NovoTTF-100L and NovoTTF-200T devices in 276 metastatic NSCLC patients showed an increase in the overall survival of patients who received TTFields in combination with standard of care therapies compared to the patients that received standard of care therapies alone.

A similar device, NovoTTF-200A (also called Optune^®), delivers TTFields to the brain and was approved by the FDA under the Premarket Approval (PMA) pathway for the treatment of adults with recurrent and newly diagnosed glioblastoma, a type of aggressive primary brain tumor. Optune has a CE Mark in Europe for the treatment of glioblastoma, and is also approved in Japan and Greater China. For the treatment of malignant pleural mesothelioma (MPM), Optune Lua^® has a CE Mark in Europe and was FDA approved under the Humanitarian Device Exemption (HDE) pathway for this use, in the United States.

Based on the science behind TTFields and the clinical results to date, NovoTTF-200T is not expected to have systemic side effects in patients suffering from NSCLC. In previous studies performed with Optune®, the device investigated in glioblastoma, a high percentage of patients have experienced local skin irritation beneath the transducer arrays, which was mild to moderate in severity in the vast majority of cases.

In the aforementioned study for non-small cell lung cancer, there were no serious systemic side effects attributed to TTFields by the study doctors. The only device-related side effect was mild to moderate skin irritation under the arrays placed on the skin.

The information provided in this website is partial, and you should consult with your treating physician concerning the complete safety profile of TTFields.

The objective of this study is to evaluate the safety and efficacy of Tumor Treating Fields (TTFields), delivered by the NovoTTF-200T device, together with pembrolizumab in subjects with metastatic NSCLC previously treated with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.

Please contact an investigator at the study center closest to you. You may also contact Novocure, the study sponsor, if you need assistance reaching a study center [Contact Us].

The use of NovoTTF-200T is not expected to have systemic side effects, based on our clinical data to date. Some patients have experienced skin irritation beneath the transducer arrays. When TTFields are delivered, the arrays may cause mild warming and tingling of the skin underneath them.

Please consult with a study physician at one of the participating centers for additional information about potential side effects from using NovoTTF-200T and the other treatments in the LUNAR-4 clinical study.

Patients may not necessarily be physically carrying the device most of the time, but will rather use it while it is continuously placed in one location (e.g. on a desk, a table or on the floor inside the carrying bag). The device was designed to allow the performance of normal daily routines. The device and the portable battery weigh about 1.3 kilograms, or 2.7 pounds, altogether and can be carried in a dedicated shoulder bag or backpack when walking around.

There is no exposure of TTFields to non-users, such as co-workers and family members. The use of the device will not interfere with household or standard personal electrical devices.

You can use the device while maintaining most of your daily routines. The arrays may be concealed underneath your clothes. The Device Support Specialist (DSS) will offer help and support related to appearance issues if you are using TTFields.