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

Key Who May Qualify: - Newly diagnosed diagnosed by tissue sample (biopsy-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. - For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay. - No treatment for newly diagnosed GBM other than surgery followed by standard-of-care adjuvant postoperative radiation (54 to 60 Gy) and TMZ chemotherapy. - At least 4 weeks since completion of radiation therapy, with a post-radiation MRI showing no progression. Key Who Should NOT Join This Trial: - 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. - Intent to use Optune® (TTF). - Significant other uncontrolled health conditions or other malignancies. Always talk to your doctor about whether this trial is right for you.