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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• silevertinib in combination with temozolomide (Drug): Participants 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) (Drug): Participants 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

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan
• radiation: Part of the study plan

Main goals

• Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) (12 months)

Other goals

• Overall Survival

Planned enrollment: 162 (estimated).

• University of Alabama at Birmingham O'Neal Comprehensive Cancer Center, Birmingham, Alabama
• Highlands Oncology Group, Springdale, Arkansas
• UCSD Moores Cancer Center, La Jolla, California
• Cedars-Sinai Medical Center, Los Angeles, California
• UC Irvine Health, Orange, California
• Stanford University, Palo Alto, California
• Yale Cancer Center, New Haven, Connecticut
• Johns Hopkins Sibley Memorial Hospital, Washington D.C., District of Columbia
• Miami Cancer Institute, Miami, Florida
• Moffitt Cancer Center, Tampa, Florida
• Piedmont Oncology Research, Atlanta, Georgia
• Johns Hopkins Sidney Kimmel Cancer Center - Baltimore, Baltimore, Maryland
• Massachusetts General Hospital, Boston, Massachusetts
• Beth Israel Deaconess Medical Center, Boston, Massachusetts
• Dana Farber Cancer Institute, Boston, Massachusetts
• University of Michigan, Ann Arbor, Michigan
• Henry Ford Cancer- Detroit, Detroit, Michigan
• Washington University School of Medicine Siteman Cancer Center, St Louis, Missouri
• University of Nebraska Medical Center, Omaha, Nebraska
• John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey
• Rutgers Cancer Institute, New Brunswick, New Jersey
• Atlantic Health, Summit, New Jersey
• Northwell Health Center for Advanced Medicine - Brain Tumor Center, Lake Success, New York
• Columbia University Irving Medical Center, New York, New York
• Montefiore Medical Center, The Bronx, New York
• Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio
• Ohio State University, Columbus, Ohio
• Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Philadelphia, Pennsylvania
• UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania
• Prisma Health, Greenville, South Carolina
• UT MD Anderson Cancer Center, Houston, Texas
• Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
• Inova Schar Cancer Institute, Fairfax, Virginia
• VCU Massey Comprehensive Cancer Center, Richmond, Virginia
• University of Wisconsin Carbone Cancer Center, Madison, Wisconsin

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07326566

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 22, 2026. Public record; not medical advice.