Pivotal, Randomized, Open-label Study of Optune® (Tumor Treating Fields) Concomitant With RT & TMZ for the Treatment of Newly Diagnosed GBM

Summary

Objectives

Optune® is a medical device that has been approved for the treatment of recurrent and
newly diagnosed glioblastoma (GBM) by the Food and Drug Administration (FDA) in the
United States. Optune® has obtained a CE mark in Europe for recurrent and newly diagnosed
GBM.

The current standard of care for GBM includes the addition of Optune® to maintenance
temozolomide (TMZ), following the completion of radiation therapy (RT).

The purpose of the current study is to test if the earlier introduction of Optune®, at
the time of radiation therapy (which is given together with temozolomide), improves
clinical outcomes compared to the standard of care.

The study will randomize 950 subjects equally to one of two treatment arms:

1. Treatment arm I: Patients receive TTFields at 200 kHz to the brain using the Optune®
System together with RT and TMZ, followed by maintenance TMZ concomitant with the
Optune® treatment.

2. Treatment arm II: Patients receive RT and TMZ alone, followed by maintenance TMZ
concomitant with TTFields at 200 kHz to the brain using the Optune®.

All patients are to receive standard RT and TMZ treatment followed by maintenance TMZ
chemotherapy and Optune® according to the current standard of care regimen.

Optune® will continue until second disease progression per RANO Criteria or 24 months
(the earlier of the two) unless any of the treatment discontinuation conditions described
under criteria for patient withdrawal or termination are met.

After surgery or biopsy, subjects that would like to participate will be required to
submit samples of their tumor to a lab for testing. The results of this test will be used
for randomization into the trial.

If the subject is assigned to the treatment group that will start Optune® therapy during
radiation therapy, Optune® therapy will begin within 7 days of enrolling in the study and
no later than the first day of RT and TMZ treatment.

After the initial visit, subjects will continue treatment at home, while pursuing normal
daily routines. Subjects are required to use the device for at least 18 hours a day.
Short breaks in treatment for personal hygiene and other personal needs is allowed. Total
usage time will be recorded and provided to the sponsor.

Subjects will be required to return to the clinic every 4 weeks until study participation
ends. Once every 8 weeks until the tumor potentially returns twice, subjects will have a
contrast MRI of the head and neurological exam performed for the first 6 months of the
study and then at least every three months until a total time period of 24 months.Once
every 12 weeks until second disease progression, subjects will also fill out a quality of
life questionnaire.

After the second time the tumor returns, subjects will return to the clinic for one final
visit approximately 30 days after the last treatment with Optune®.

After discontinuing Optune® subjects will be contacted once per month by telephone to
answer basic questions about their health status.