Silevertinib plus temozolomide for newly diagnosed GBM with unmethylated MGMT and EGFRvIII

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 2, two-part trial in adults with newly diagnosed, IDH‑wildtype glioblastoma who have completed surgery and standard postoperative radiation with temozolomide. Part 1 is a small safety lead-in (about 12 participants) to find a tolerable dose of silevertinib given with temozolomide; Part 2 randomizes roughly 150 participants to receive either silevertinib plus temozolomide or temozolomide alone in 28‑day cycles. Eligible participants for the randomized portion must have EGFRvIII-positive tumors and an unmethylated MGMT promoter, with no tumor progression on a post‑radiation MRI. The primary outcome focuses on length of time participants live without disease progression while receiving maintenance therapy.

Why it matters

Who can join: the full rules

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.

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.

Where it's running

• University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
  Birmingham, Alabama, United States Recruiting
• Highlands Oncology Group
  Springdale, Arkansas, United States Recruiting
• UCSD Moores Cancer Center
  La Jolla, California, United States Recruiting
• Cedars-Sinai Medical Center
  Los Angeles, California, United States Recruiting
• UC Irvine Health
  Orange, California, United States Recruiting
• Stanford University
  Palo Alto, California, United States Recruiting

Study contacts

• Study coordinator: Black Diamond Therapeutics Clinical Trial Navigation Service
• Email: blackdiamondtx@careboxhealth.com
• Phone: (866) 955-4397

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.