RecruitingPhase 2

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

United States162 participantsStarted 2026-05-05

Plain-language 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?

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this trial specifically requires that my tumor be EGFRvIII-positive and have unmethylated MGMT, how will my doctor test for these markers, and have my results already confirmed I have both?
2This is a Phase 2 trial, which means silevertinib is still being studied for safety and effectiveness in people — what do we know so far about its side effect profile, especially combined with temozolomide, which I may already be familiar with as a standard GBM treatment?
3The trial is measuring progression-free survival as its main goal — what does that mean in practical terms for me, and how does that compare to what I might expect from standard chemoradiation alone for newly diagnosed GBM with unmethylated MGMT?
4Unmethylated MGMT is known to respond less well to temozolomide on its own — does my doctor think targeting EGFRvIII with silevertinib could make a meaningful difference for my specific tumor profile, or is standard treatment still the more established path right now?
5What would participating in this trial actually look like for my daily life — how often would I need to come in for treatment and monitoring, and if my disease progresses on the trial, what options would still be available to me?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

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

Timeframe: 12 months

Trial details

NCT IDNCT07326566

SponsorBlack Diamond Therapeutics, Inc.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2028-11

Contact for this trial

Black Diamond Therapeutics Clinical Trial Navigation Service

(866) 955-4397 blackdiamondtx@careboxhealth.com

View on ClinicalTrials.gov More Glioblastoma (GBM) trials