Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-triggered Expansion Cohort

Conditions
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High Grade Glioma

Intervention / Treatment
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* Drug: BDTX-1535


Participation Criteria
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Eligibility Criteria
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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. Adequate archival or biopsy tissue available for testing of EGFR alterations. Participants must have measurable disease preoperatively. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale. Ability to swallow oral medications. Participant has adequate bone marrow and organ function Exclusion Criteria: Pregnancy or breastfeeding. Known allergic reactions to components of the BDTX-1535. 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. Known active systemic bacterial infection, fungal infection, or detectable viral infection . Significant cardiovascular disease. Symptomatic or radiographic leptomeningeal disease. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study . Concurrent use of prohibited medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recurrent high-grade glioma participants with EGFR alterations<br> | Drug: BDTX-1535<br>* BDTX-1535 is an inhibitor of EGFR mutations<br>|
| Experimental: Recurrent high-grade glioma participants with EGFR fusion<br> | Drug: BDTX-1535<br>* BDTX-1535 is an inhibitor of EGFR mutations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unbound concentration of BDTX-1535 in tumor tissue | Unbound BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue | Phase 0 Intraoperative Sample | 
| Total concentration of BDTX-1535 in tumor tissue | Total BDTX-1535 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue | Phase 0 Intraoperative Sample | 
| Progression Free Survival (PFS) | Rate of 6-month progression-free survival | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of BDTX-1535 in CSF | BDTX-1535 level in CSF will be determined | Phase 0 Intraoperative sample | 
| Percentage of pEGFR positive cells in tumor tissue | Expression of pEGFR in BDTX-1535 treated HGG tissue compared to archival tissue. | Phase 0 Intraoperative Sample | 
| Percentage of pERK positive cells in tumor tissue | Expression of pERK in BDTX-1535 treated HGG tissue compared to archival tissue. | Phase 0 Intraoperative Sample | 
| Overall survival (OS) | Median overall survival in participants with demonstrated PK effect | Up to 12 months after the last study dose | 
| Safety and tolerability - adverse events | Number of adverse events through study completion | Up to 30 days after the last study dose | 
| Safety and tolerability - death | Number of deaths | 24 months | 
| Clinical laboratory abnormalities per CTCAE | Incidence of Clinical laboratory abnormalities per CTCAE | Up to 30 days after the last study dose |