Study of Silevertinib With Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT 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. 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?

Interventions

• 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

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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.

Sites (25)

• University of Alabama at Birmingham O'Neal Comprehensive Cancer Center, Birmingham, Alabama · RECRUITING
• Highlands Oncology Group, Springdale, Arkansas · RECRUITING
• Cedars-Sinai Medical Center, Los Angeles, California · RECRUITING
• Stanford University, Palo Alto, California · RECRUITING
• Yale Cancer Center, New Haven, Connecticut · RECRUITING
• Johns Hopkins Sibley Memorial Hospital, Washington D.C., District of Columbia · RECRUITING
• Miami Cancer Institute, Miami, Florida · RECRUITING
• Moffitt Cancer Center, Tampa, Florida · RECRUITING
• Johns Hopkins Sidney Kimmel Cancer Center - Baltimore, Baltimore, Maryland · RECRUITING
• Massachusetts General Hospital, Boston, Massachusetts · RECRUITING
• Beth Israel Deaconess Medical Center, Boston, Massachusetts · RECRUITING
• Dana Farber Cancer Institute, Boston, Massachusetts · RECRUITING
• Henry Ford Cancer- Detroit, Detroit, Michigan · RECRUITING
• Washington University School of Medicine Siteman Cancer Center, St Louis, Missouri · RECRUITING
• John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey · RECRUITING
• Rutgers Cancer Institute, New Brunswick, New Jersey · RECRUITING
• Atlantic Health, Summit, New Jersey · RECRUITING
• Northwell Health Center for Advanced Medicine - Brain Tumor Center, Lake Success, New York · RECRUITING
• Columbia University Irving Medical Center, New York, New York · RECRUITING
• Montefiore Medical Center, The Bronx, New York · RECRUITING
• Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center, Philadelphia, Pennsylvania · RECRUITING
• UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania · RECRUITING
• Prisma Health, Greenville, South Carolina · RECRUITING
• Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah · RECRUITING
• Inova Schar Cancer Institute, Fairfax, Virginia · RECRUITING