Clinical Trial 24148

• Overview

  Study Title:

  A Phase 2 Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Silevertinib, an Oral EGFR Inhibitor, in Combination with Temozolomide in Patients with Newly Diagnosed Glioblastoma with Unmethylated MGMT Promoter and EGFRvIII

  Summary:

  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.

  Objective:

  Primary *To compare the PFS of patients with newly diagnosed GBM with unmethylated MGMT promoter and EGFRvIII treated with silevertinib and TMZ or TMZ alone, administered as maintenance therapy post-adjuvant chemoradiation. Secondary *To compare the OS of patients with newly diagnosed GBM with unmethylated MGMT promoter and EGFRvIII treated with silevertinib and TMZ or TMZ alone, administered as maintenance therapy post-adjuvant chemoradiation. *Part 1 Only: To determine a RP2CD of silevertinib and TMZ to study in a randomized trial. *To assess the safety and tolerability of the combination of silevertinib and TMZ. To characterize the PK of the combination of silevertinib and TMZ.

• Treatments

  Therapies:

  Chemotherapy (NOS); EGFR Inhibitor

  Medications:

  Silevertinib (); Temodal (Temozolomide); Temozolomide ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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.
  • 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.

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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.

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