Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII

Silevertinib was designed to block a growth signal important to some cancers where tumors

grow because of changes in a protein called epidermal growth factor receptor (EGFR).

These changes are called gene amplifications, mutations, or alterations and are found in

tumors. Temozolomide is a drug that fights cancer cells by damaging DNA (the genetic

material of cells), which could cause the tumor cells to die. It is the standard

treatment for adults with certain types of newly diagnosed brain cancer, like GBM. It is

given together with radiotherapy and sometimes afterward as maintenance therapy.

This study has 2 parts. To be eligible for the study, participants must have received a

diagnosis of GBM, had surgery to remove or reduce the size of the tumor, and received

adjuvant radiation therapy and temozolomide. No other prior treatments for GBM are

allowed.

In Part 1 (called the Safety Lead-in), participants will receive silevertinib combined

with temozolomide to determine if the combination is safe and to find the best dose.

Approximately 12 participants are expected to enroll in Part 1 of the study.

In Part 2, all participants will be randomized to one of two different treatment groups:

- Group 1: Silevertinib + temozolomide

- Group 2: Temozolomide only

Approximately 150 participants are expected to be randomized in Part 2 of the study.

In both Part 1 and Part 2, the study treatment will be given in "cycles". Each cycle will

be 28 days. After a cycle ends, the next cycle will immediately begin the next day. Both

silevertinib and temozolomide will be taken orally. Silevertinib is taken daily until

disease progression and temozolomide is taken for the first 5 days of each cycle (up to 6

cycles).

If participants are found to be eligible for the study and enrolled (in Part 1) or

randomized (in Part 2), participants will:

- Take the study drug as directed

- Return for frequent clinic visits to monitor overall health and status of GBM

- Undergo imaging and other laboratory tests to determine status of GBM

- Complete a paper diary at home to record the date and time(s) that the study drug is

taken