People diagnosed with glioblastoma often face difficult treatment decisions and a need for additional treatment options. A new Phase 2 clinical trial is evaluating silevertinib in combination with temozolomide (TMZ) in adults with newly diagnosed glioblastoma with EGFRvIII and unmethylated MGMT promoter status. The study is designed to determine whether adding silevertinib to TMZ can help delay tumor growth or recurrence following initial therapy.
Understanding EGFRvIII and Silevertinib
Glioblastoma tumors can contain different genetic changes (mutations) that help drive tumor growth. About half of glioblastoma tumors have changes in a gene called epidermal growth factor receptor (EGFR). EGFR is a protein that helps control cell growth and division. When EGFR is altered, cells can grow too quickly and avoid dying, which may lead to cancer. EGFRvIII is the most common EGFR alteration found in glioblastoma.
Silevertinib is an investigational oral medicine being studied for cancers driven by EGFR alterations. Unlike standard chemotherapy, which affects rapidly dividing cells more broadly, silevertinib is intended to target specific EGFR alterations, including EGFRvIII.
Understanding MGMT Promoter Methylation and Temozolomide (TMZ)
Another important factor in this study is MGMT promoter methylation status, which helps predict how well TMZ may work. TMZ is an oral chemotherapy that damages the DNA of cancer cells, which may cause tumor cell death. If the MGMT promoter is “on” (unmethylated), the tumor can repair the damage from TMZ, so the treatment may not work as well.
About the Study
The BDTX-1535-201 study (NCT07326566) is enrolling adults who have been newly diagnosed with glioblastoma and have completed standard initial treatment, including surgery, radiation therapy, and TMZ chemotherapy. Eligible participants must have tumors that are positive for EGFRvIII and have an unmethylated MGMT promoter.
The study began with a safety lead-in (Part 1), which was designed to establish a safe and appropriate dose of silevertinib in combination with TMZ for the randomized Part 2 portion of the trial. Approximately 150 participants are expected to enroll in Part 2.
Participants in Part 2 are randomly assigned to one of two treatment groups:
- Silevertinib plus TMZ
- TMZ alone
The main goal of this study is to learn whether adding silevertinib to TMZ can help keep glioblastoma from growing. Researchers will also study the side effects of taking silevertinib with TMZ and whether the combination helps patients live longer as compared to treatment with TMZ alone.
How Do I Learn More About the Study?
Silevertinib is an investigational medicine and has not been approved for treatment of glioblastoma or any other disease. Individuals interested in learning more about the trial should speak with their healthcare team.
Resources and Additional Information
- American Brain Tumor Association. Clinical Trial NCT07326566. ABTA Clinical Trials Finder. https://www.abta.org/find-clinical-trials/#/study/NCT07326566
- ClinicalTrials.gov. Study of Silevertinib with Temozolomide for the Treatment of Newly Diagnosed GBM With Unmethylated MGMT and EGFRvIII (NCT07326566). https://clinicaltrials.gov/study/NCT07326566
- Black Diamond Therapeutics. Silevertinib for Glioblastoma (GBM). https://blackdiamondtherapeutics.com/pipeline-programs/silevertinib-gbm
- National Brain Tumor Society. Telling the Truth, the Whole Truth, and Nothing but the Truth on EGFR. https://braintumor.org/news/telling-the-truth-the-whole-truth-and-nothing-but-the-truth-on-egfr/
- National Brain Tumor Society. Let’s Talk About MGMT. https://braintumor.org/news/lets-talk-about-mgmt/
