Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions
Study Details
Study Description
Brief Summary
This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma. BDTX-1535 was designed to block a growth signal important to some cancers. BDTX-1535 is being tested in this study to see if it can be given safely to people who have tumors that can be dependent on that growth signal because of changes in a protein called EGFR. These gene changes are called amplifications, mutations, fusions or alterations and are found only in the tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Early Phase 1 |
Detailed Description
Eligible participants will enroll in the Phase 0 study and receive BDTX-1535 prior to a planned resection. During surgery, blood, tumor, and CSF samples will be collected to measure the amount of drug that is present in the samples. Participants with tumors demonstrating PK response will continue with once-daily BDTX-1535 treatment, continuously in 28-day cycles after surgery. Participants will continue to receive BDTX-1535 until the progression of disease, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Recurrent high-grade glioma participants with EGFR alterations
|
Drug: BDTX-1535
BDTX-1535 is an inhibitor of EGFR mutations
|
| Experimental: Recurrent high-grade glioma participants with EGFR fusion
|
Drug: BDTX-1535
BDTX-1535 is an inhibitor of EGFR mutations
|
Outcome Measures
Primary Outcome Measures
- Unbound concentration of BDTX-1535 in tumor tissue [Phase 0 Intraoperative Sample]
Unbound BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
- Total concentration of BDTX-1535 in tumor tissue [Phase 0 Intraoperative Sample]
Total BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue
- Progression Free Survival (PFS) [6 months]
Rate of 6-month progression-free survival
Secondary Outcome Measures
- Concentration of BDTX-1535 in CSF [Phase 0 Intraoperative sample]
BDTX-1535 level in CSF will be determined
- Percentage of pEGFR positive cells in tumor tissue [Phase 0 Intraoperative Sample]
Expression of pEGFR in BDTX-1535 treated HGG tissue compared to archival tissue.
- Percentage of pERK positive cells in tumor tissue [Phase 0 Intraoperative Sample]
Expression of pERK in BDTX-1535 treated HGG tissue compared to archival tissue.
- Overall survival (OS) [Up to 12 months after the last study dose]
Median overall survival in participants with demonstrated PK effect
- Safety and tolerability - adverse events [Up to 30 days after the last study dose]
Number of adverse events through study completion
- Safety and tolerability - death [24 months]
Number of deaths
- Clinical laboratory abnormalities per CTCAE [Up to 30 days after the last study dose]
Incidence of Clinical laboratory abnormalities per CTCAE
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants who have had a prior resection of diagnosed HGG (2021 WHO grade 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy.
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Adequate archival or biopsy tissue available for testing of EGFR alterations.
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Participants must have measurable disease preoperatively.
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Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale.
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Ability to swallow oral medications.
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Participant has adequate bone marrow and organ function
Exclusion Criteria:
-
Pregnancy or breastfeeding.
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Known allergic reactions to components of the BDTX-1535.
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Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis, as determined by the investigator.
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Known active systemic bacterial infection, fungal infection, or detectable viral infection .
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Significant cardiovascular disease.
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Symptomatic or radiographic leptomeningeal disease.
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Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study .
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Concurrent use of prohibited medications.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St. Joseph's Hospital and Medical Center | Phoenix | Arizona | United States | 85013 |
Sponsors and Collaborators
- St. Joseph's Hospital and Medical Center, Phoenix
- Ivy Brain Tumor Center
- Barrow Neurological Institute
Investigators
- Principal Investigator: Nader Sanai, MD, Chief Scientific Officer/Director of the Ivy Brain Tumor Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2023-20
- 24-500-090-34-38