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

May 26, 2026 updated by: Black Diamond Therapeutics, Inc.

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

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?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Silevertinib was designed to block a growth signal important to some cancers where tumors grow because of changes in a protein called epidermal growth factor receptor (EGFR). These changes are called gene amplifications, mutations, or alterations and are found in tumors. Temozolomide is a drug that fights cancer cells by damaging DNA (the genetic material of cells), which could cause the tumor cells to die. It is the standard treatment for adults with certain types of newly diagnosed brain cancer, like GBM. It is given together with radiotherapy and sometimes afterward as maintenance therapy.

This study has 2 parts. To be eligible for the study, participants must have received a diagnosis of GBM, had surgery to remove or reduce the size of the tumor, and received adjuvant radiation therapy and temozolomide. No other prior treatments for GBM are allowed.

In Part 1 (called the Safety Lead-in), participants will receive silevertinib combined with temozolomide to determine if the combination is safe and to find the best dose. Approximately 12 participants are expected to enroll in Part 1 of the study.

In Part 2, all participants will be randomized to one of two different treatment groups:

  • Group 1: Silevertinib + temozolomide
  • Group 2: Temozolomide only

Approximately 150 participants are expected to be randomized in Part 2 of the study.

In both Part 1 and Part 2, the study treatment will be given in "cycles". Each cycle will be 28 days. After a cycle ends, the next cycle will immediately begin the next day. Both silevertinib and temozolomide will be taken orally. Silevertinib is taken daily until disease progression and temozolomide is taken for the first 5 days of each cycle (up to 6 cycles).

If participants are found to be eligible for the study and enrolled (in Part 1) or randomized (in Part 2), participants will:

  • Take the study drug as directed
  • Return for frequent clinic visits to monitor overall health and status of GBM
  • Undergo imaging and other laboratory tests to determine status of GBM
  • Complete a paper diary at home to record the date and time(s) that the study drug is taken

Study Type

Interventional

Enrollment (Estimated)

162

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Recruiting
        • Highlands Oncology Group
        • Contact:
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University School of Medicine Siteman Cancer Center
        • Contact:
    • New Jersey
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
    • South Carolina
      • Greenville, South Carolina, United States, 29605

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: silevertinib and temozolomide
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
Drug: silevertinib in combination with temozolomide
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.
Other Names:
  • Temodar
  • TMZ
  • BDTX-1535
Active Comparator: temozolomide
temozolomide 150-200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle for maximum of 6 cycles
Drug: temozolomide (TMZ)
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
Other Names:
  • Temodar
  • TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
Time Frame: 12 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 18 months
Overall survival defined as time from first dose of study drug to death from any cause.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Black Diamond Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

January 7, 2026

First Submitted That Met QC Criteria

January 7, 2026

First Posted (Actual)

January 8, 2026

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 26, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BDTX-1535-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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