Study of Silevertinib With Temozolomide for the Treatment of 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
1 other identifier
interventional
162
1 country
4
Brief 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?
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2026
Typical duration for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 7, 2026
CompletedFirst Posted
Study publicly available on registry
January 8, 2026
CompletedStudy Start
First participant enrolled
April 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2029
April 29, 2026
March 1, 2026
2.6 years
January 7, 2026
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.
12 months
Secondary Outcomes (1)
Overall Survival
18 months
Study Arms (2)
silevertinib and temozolomide
EXPERIMENTALsilevertinib 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
ACTIVE COMPARATORtemozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
Interventions
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
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Highlands Oncology Group
Springdale, Arkansas, 72762, United States
Atlantic Health
Summit, New Jersey, 07901, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Black Diamond Therapeutics Clinical Trial Navigation Service
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 7, 2026
First Posted
January 8, 2026
Study Start
April 1, 2026
Primary Completion (Estimated)
November 1, 2028
Study Completion (Estimated)
March 1, 2029
Last Updated
April 29, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share