The purpose of this study is to see if combining silevertinib with temozolomide after surgery and radiotherapy helps treat newly diagnosed glioblastoma (GBM) better than using temozolomide alone in the maintenance setting.
Specifically, this study is being done to find answers to the following questions:
* How much of the study drugs (silevertinib combined with temozolomide) should be given to participants with GBM? * What are the side effects participants have when taking the study drug (silevertinib combined with temozolomide)? * Can the study drug (silevertinib combined with temozolomide) help participants with GBM live longer without disease progression compared to treatment with temozolomide alone?
Newly diagnosed histologically confirmed glioblastoma that is isocitrate dehydrogenase wild type (IDH-WT).
Positive EGFR status in the brain tumor as determined by a commercially available test or validated laboratory assay (CLIA or comparable certification).
For Part 1 (Safety Lead-in) ONLY: EGFR alterations.
For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.
Recurrent multifocal disease, metastatic, leptomeningeal, or extracranial GBM, or gliomatosis cerebri.
Progression of GBM prior to Enrollment, Screening, or Randomization.
Biopsy-only/no resectional surgery.
Prior or concomitant treatment for GBM with an EGFR-targeting agent, including silevertinib, bevacizumab, cytotoxic chemotherapy, immunotherapy, experimental therapies, Gliadel wafers, GammaTile®, or other intratumoral or intracavitary antineoplastic therapy.
Parallel
silevertinib in combination with temozolomide
DrugParticipants enrolled into Part 1 (Safety Lead-In) or randomized to Arm A in Part 2 will receive silevertinib at dose determined in Part 1 until disease progression in combination with temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles.
temozolomide (TMZ)
DrugParticipants randomized to Arm B will receive temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.
Overall Survival
Overall survival defined as time from first dose of study drug to death from any cause.
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