Silevertinib plus temozolomide for newly diagnosed GBM with unmethylated MGMT and EGFRvIII
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
This trial tests whether adding silevertinib to standard temozolomide helps people with newly diagnosed glioblastoma that have EGFRvIII and an unmethylated MGMT promoter live longer without the cancer getting worse.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 162 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Black Diamond Therapeutics, Inc. Industry-sponsored |
| Drugs / interventions | bevacizumab, silevertinib, chemotherapy, immunotherapy, radiation |
| Locations | 5 sites (Springdale, Arkansas and 4 other locations) |
| Trial ID | NCT07326566 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults with newly diagnosed, IDH‑wildtype glioblastoma who are EGFR‑positive (and for randomization specifically EGFRvIII‑positive and MGMT‑unmethylated), who have completed surgery and standard postoperative radiation with temozolomide and have no radiographic progression at least four weeks after radiation are potential candidates.
Not a fit: Patients with methylated MGMT, non‑EGFRvIII tumors, recurrent or multifocal/leptomeningeal/extracranial GBM, biopsy‑only diagnosis, or progression before enrollment are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, adding silevertinib to temozolomide could help people with EGFRvIII, unmethylated‑MGMT GBM stay progression‑free longer than with temozolomide alone.
How similar studies have performed: Previous EGFR‑targeted approaches in glioblastoma have shown limited success, so combining a next‑generation EGFR inhibitor like silevertinib with temozolomide is relatively novel and not yet proven.
Eligibility criteria
Show full inclusion / exclusion 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. 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 this trial is running
Springdale, Arkansas and 4 other locations
- Highlands Oncology Group — Springdale, Arkansas, United States (Recruiting)
- Cedars-Sinai Medical Center — Los Angeles, California, United States (Recruiting)
- Atlantic Health — Summit, New Jersey, United States (Recruiting)
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Recruiting)
Study contacts
- Study coordinator: Black Diamond Therapeutics Clinical Trial Navigation Service
- Email: blackdiamondtx@careboxhealth.com
- Phone: (866) 955-4397
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.