KEYNOTE B36 – Lung Cancer Clinical Trial

overview

The KEYNOTE B36 study is intended for patients who have been diagnosed with, but have not been treated for, PD-L1 positive advanced or metastatic non-small cell lung cancer (NSCLC). This clinical study is evaluating the safety and efficacy of Tumor Treating Fields (TTFields) delivered by the NovoTTF-200T device concomitant with standard immunotherapy, pembrolizumab, compared to  pembrolizumab alone for first line treatment of patients with advanced or metastatic NSCLC. [The KEYNOTE B36 study].

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 KEYNOTE B36 study, please contact one of the participating centers [KEYNOTE B36 CENTERS] as soon as possible.

about TTFields  

Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division [Science of TTFields]. 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.

TTFields are delivered to the body region where the 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 [Living with TTFields].

NovoTTF-200T for the treatment of non-small cell lung cancer is investigational; it has not been approved by the U.S. Food and Drug Administration (FDA). 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 KEYNOTE B36 study

The KEYNOTE B36 study is pilot, randomized, open-label study designed to evaluate the safety and effectiveness of TTFields, generated by the medical device NovoTTF-200T [About TTFields]. Study patients will receive pembrolizumab for first line treatment of advanced or metastatic non-small cell lung cancer (NSCLC) alone or concomitantly administered with the TTField device. The study is expected to enroll 100 patients. The study will enroll patients in multiple medical centers across North America. [KEYNOTE B36 Centers].

The KEYNOTE B36 Study Design

The study is intended for patients with  advanced or metastatic NSCLC that have not received previous treatment. Final eligibility can only be determined by the clinical study physician in one of the clinical study centers.

Patients will be randomized (similar to a coin toss) into one of two groups:

• TTFields Group: Patients enrolled in the TTFields group will receive continuous TTFields treatment  using NovoTTF-200T. All patients will concomitantly receive pembrolizumab, a standard immunotherapy agent, which is delivered intravenously.

• Control Group: Patients enrolled in the control group will receive pembrolizumab, a standard immunotherapy agent, delivered intravenously. Patients in this group who have disease progression will be offered to crossover to the TTFields group.

Treatment for both groups will continue for 24 months until 35 study treatments have been administered, disease progression, or if investigator or patient decide to stop treatment.

Using the Device

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 [Living with TTFields].

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.

Eligibility

For the complete list of eligibility criteria please go to clinicaltrials.gov or consult with a KEYNOTE B36 study physician:

Inclusion Criteria (summary, not complete list) 

1. Diagnosed with stage III or metastatic NSCLC
2. Has a PD-L1 positive (TPS≥1%) tumor
3. Has not received prior treatments for advanced or metastatic NSCLC (palliative treatment and adjuvant or neoadjuvant chemotherapy for non-metastatic disease that were completed greater than 12 mo. prior to advanced or metastatic disease are allowed)
4. At least 22 years of age

Exclusion Criteria (summary, not complete list) 

1. Has an EGFR sensitizing mutation and/or ALK translocation
2. Can be treated with curative intent with either surgical resection and/or chemoradiation
3. Has received prior systemic anti-cancer therapy or prior radiotherapy for advanced or metastatic NSCLC (However, therapy for non-metastatic disease, if completed 12 months prior to diagnosis with advanced or metastatic NSCLC, is allowed.)
4. Being unable to operate the NovoTTF-200T device independently or with the help of a caregiver
5. Current pregnancy
6. Significant illnesses not associated with the primary disease
7. Implanted electronic devices (e.g. pacemaker) in the upper torso

Enrollment

Expected total enrollment is 100 patients. The study will enroll patients in multiple medical centers in North America. Please contact one of them as soon as possible if you would like to participate in the KEYNOTE B36 study. 

Study Costs

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 will also reimburse patients for reasonable travel costs directly related to the study’s procedures. Such reimbursements are done according to the policy of the study center at which the patient is being treated. Prior to enrolling in the study, please consult with the clinical study team at the center about the local reimbursement policy and your rights.

living with TTFields

Patients participating in the KEYNOTE B36 study in the TTFields group 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 technical support, they do not offer medical advice. Please direct all medical questions to your study clinician.

Using the NovoTTF-200T Device

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.

What does it look like?

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 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.

Portability

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.

science of TTFields

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 thorax multiply at a much slower rate, if at all.

TTFields Mechanism of Action

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:

TTFIELDS ARE NOT APPROVED FOR THE TREATMENT OF ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER IN THE UNITED STATES. THE SAFETY AND EFFICACY OF TTFIELDS FOR THIS INDICATION HAS NOT BEEN ESTABLISHED.

Past Clinical Experience

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(P), a previous model of NovoTTF-200T, has been evaluated in a pilot study of 42 patients with inoperable non-small cell lung cancer patients who received TTFields together with standard chemotherapy to evaluate the safety of TTFields in this indication.

A similar device, NovoTTF-200A (also called Optune®), delivers TTFields to the brain and is 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.

Side Effects

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 by the study doctors to TTFields. The only side effect which was related to the device 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.

FAQ  

What is the objective of this study?

This pilot study is designed to evaluate the safety and efficacy of TTFields concomitant with pembrolizumab, a standard immunotherapy agent, compared to pembrolizumab alone for first line treatment of patients with advanced or metastatic NSCLC.

How can I participate in the KEYNOTE B36 study?

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].

What are the expected side effects of TTFields?

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. For more information, see Science of TTFields.

Please consult with a study physician at one of the centers participating in the study for additional information about potential side effects from using NovoTTF-200T and the other treatments in the KEYNOTE B36 clinical study [KEYNOTE B36 Centers].

Do I need to carry the device all the time?

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.

Will the use of TTFields pose any risk to family members or other people?

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.

How will the device affect my social life?

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. For additional information, please see Living with TTFields.