High Grade GliomaEarly Phase 1NCT06072586
A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (rHGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions
A Early Phase 1 study testing BDTX-1535, BDTX-1535 combined with radiation therapy and BDTX-1535 combined with temozolomide and radiation therapy in people with High Grade Glioma and Glioblastoma, run by St. Joseph's Hospital and Medical Center, Phoenix at 2 sites in United States.
Trial summary
This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma (nGBM). BDTX-1535 was designed to block a growth signal important to some cancers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Grade Glioma, Glioblastoma
- What is being tested?
- BDTX-1535, BDTX-1535 combined with radiation therapy and BDTX-1535 combined with temozolomide and radiation therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Oct 2023to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Arms A \& B: Recurrent high grade glioma (2021 WHO Grades 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy.
- Arm C, D, \& E: Newly diagnosed glioblastoma (2021 WHO Grade 4), who have not received any tumor directed intervention other than biopsy or resection.
- Candidate for clinical resection of rHGG (Arms A \& B) or nGBM (Arms C \& D).
- Adequate archival or biopsy tissue available for testing of EGFR alterations. The tissue must have evidence of EGFR alterations including variants, fusion, and mutations with or without amplifications. rHGG participants with EGFR fusion will be solely enrolled into Arm B.
- Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
- Provision of signed and dated, written informed consent (personally or by the legally authorized representative, if applicable) prior to any study specific procedures, sampling and analyses.
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- Age ≥ 18 at time of consent
- 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 as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL (at time of surgery)
- Hemoglobin ≥ 8.5 g/dL (Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)
- Total bilirubin ≤ 1.5 X ULN (Participants with Gilbert's syndrome with a total bilirubin ≤ 3.0 times ULN and direct bilirubin within normal limits are permitted.)
- AST (SGOT) ≤ 3 X institutional ULN
- ALT (SGPT) ≤ 3 X institutional ULN
- Serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance ≥ 60 mL/min (calculated using Institutional standard method)
- Participants on corticosteroids at baseline must be on stable or decreasing doses for at least 5 days prior to Day 1.
- Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
- For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation until the end of treatment administration and for 16 weeks after the last dose of study drug.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner until the end of treatment administration and for 16 weeks after the last dose of study drug.
- Agreement to adhere to Lifestyle Considerations throughout study duration.
Who cannot join
- 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 (requiring intravenous [IV] antibiotics or fever >38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening of viral infection is not required for enrollment.
- Significant cardiovascular disease, including NYHA Class III or IV congestive heart failure, myocardial infarction, unstable angina, poorly controlled cardiac arrhythmias, or stroke in the preceding 6 months prior to study Day 1.
- 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 (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
- Concurrent use of prohibited medications: coadministration of strong CYP2C8 and CYP3A4 inhibitors and inducers with BDTX-1535. These should be discontinued 1 week or 5 half-lives (whichever is greater) prior to study Day 1. Strong inhibitors of P-gp (e.g., Amiodarone, carvedilol, dronedarone, propafenone, quinidine, ranolazine, and verapami) and BCRP (e.g., curcumin, cyclosporin A, and eltrombopag) should be used with caution. Sensitive substrates of P-gp, BCRP, and OATP should also be used with caution.
- Therapeutic intent treatment with another investigational drug or other intervention within 5 half-lives of the investigational product whichever is longer.
- With the exception of alopecia, any unresolved toxicities from prior therapy greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5) Grade 1 at the time of starting study treatment and patients with chronic Grade 2 unresolved toxicities may be eligible following discussion with the Principal Investigator.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Chandler Regional Medical Center
Chandler, Arizona, 85224
Annette Taylor, RN, 480-728-5721, annette.taylor3@commonspirit.org
Kaith Almefty, MD
- Recruiting
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Phase 0 Navigator, 602-406-8605, research@ivybraintumorcenter.org
Nader Sanai, MD
About this study
Official title: A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-triggered Expansion Cohort
This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma (nGBM). 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.
The study design includes a Phase 0 component with PK/PD-trigger for participant enrollment into an Expansion Phase 1 component. The primary objective of the Phase 0 component is to evaluate the PK endpoints of BDTX-1535. The primary objective of the Phase 1 component is to establish the safe dose of BDTX-1535 to be used in participants with a specified treatment regimen, three of which include standard of care radiotherapy for nGBM participants.
Read the detailed description
The Phase 0 component will include treatment of rHGG (Arms A and B) and nGBM participants (Arms C, D, and E) with BDTX-1535 prior to a planned tumor resection. During surgery, blood, tumor, and CSF samples will be collected to measure the amount of drug that is present in the samples. Arm A includes ascending dose levels with two cohorts, and Arm C includes two dose level cohorts to determine the Optimal Biological Dose (OBD).
The Phase 1 component will include treatment in different dose regimens. Participants with tumors demonstrating PK response (Arms A, B, and C) or PD response (Arms D and E) will continue treatment.
- Conditions
- High Grade Glioma, Glioblastoma
- Being tested
- BDTX-1535, BDTX-1535 combined with radiation therapy, BDTX-1535 combined with temozolomide and radiation therapy
- Keywords
- Silevertinib
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BDTX-1535Drug
Also called Silevertinib
BDTX-1535 is an inhibitor of EGFR mutations
BDTX-1535 combined with radiation therapyDrug
Also called Silevertinib
During Phase 1, BDTX-1535 concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT.
BDTX-1535 combined with temozolomide and radiation therapyDrug
Also called Silevertinib
During Phase 1, BDTX-1535 concurrently with standard of care upfront RT and TMZ, followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations | Experimental | Phase 0: Cohort 1 will receive 200 mg BDTX-1535 once daily (Days 1-5). Cohort 2 will receive 400 mg BDTX-1535 three times over one week (Days 1, 3, and 5). The final dose will be administered 2-4 hours before tumor resection on Day 5.
Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. Receives: Drug: BDTX-1535 |
| Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion | Experimental | Phase 0: Participants will received BDTX-1535 once daily (Days 1-5). The dose level will be determined based on PK results from Arm A, unbound drug concentration in non-enhancing tumor. The final dose will be administered 2-4 hours before tumor resection on Day 5.
Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. Receives: Drug: BDTX-1535 |
| Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination) | Experimental | Phase 0: Participants in Cohort 1 will receive 200 mg of BDTX-1535 once daily for 5 days, and participants in Cohort 2 will receive 150 mg of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. . Participants with unmethylated MGMT promoter tumors demonstrating PK response will proceed to the Phase 1 Expansion component. The OBD will be the lowest dose that achieves the following: 9 of 12 participants show PK response and 6 of 12 participants show PD response.
Phase 1: Participants with unmethylated MGMT promoter tumors demonstrating a PK response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. Receives: Drug: BDTX-1535 combined with radiation therapy |
| Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety) | Experimental | Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with unmethylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component.
Phase 1: Arm D: Participants with unmethylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. Receives: Drug: BDTX-1535 combined with radiation therapy |
| Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol) | Experimental | Phase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with methylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component.
Phase 1: Participants with methylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT and temozolomide (TMZ), followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. Receives: Drug: BDTX-1535 combined with temozolomide and radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unbound BDTX-1535 Concentration in Tumor Tissue
Unbound BDTX-1535 concentration in Gd enhancing and Gd non-enhancing tumor tissue will be determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
Measured: Intraoperative
Total BDTX-1535 Concentration in Tumor Tissue
Total BDTX-1535 concentration in Gd enhancing and Gd non-enhancing tumor tissue will be determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
Measured: Intraoperative
Incidence of DLTs Observed
Considered DLTs: Hem toxicity: 8+ days ≥G4 neutropenia/febrile neutropenia; ≥G4, or ≥G3 with clinically significant bleeding, thrombocytopenia; ≥G3 anemia requiring transfusion. Non-hem lab abnormalities: Any AR ≥G3 of ALT/AST or increase in ALT/AST >3x ULN with concurrent increase in total bilirubin >2x ULN (per Hy's Law) in pt with baseline <G1 ALT/AST; Any AR ≥G3 of ALT/AST >2x baseline or 10x ULN in pt with baseline >G2 ALT/AST due to liver mets; Non-hem dose limiting toxicity ≥G3 (per Investigator; except for G3 nausea, vomiting, or diarrhea lasting <72 hrs with adequate antiemetic/supportive care; G3 fatigue or anorexia lasting <1 week; ≥G3 electrolyte abnormality lasting up to 72 hrs, isn't clinically complicated, and resolves spontaneously or responds to intervention). AR requiring dose reduction in C1, causes >2 week delay of C2, causes 8+ day dose interruption in C1.
DLTs exclude: alopecia; lymphopenia; isolated lab changes w/o clinical sequelae or significance
Measured: From day of first dose to the end of concurrent RT treatment at 10 weeks
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by NCI-CTCAE v5
AEs that occur while participants are on study treatment.
Measured: Day of first dose until 30 days after final day of participation
Number of Participants with Treatment-Related Adverse Events (TRAEs) as Assessed by NCI-CTCAE v5
Causality will be graded using these categories: definitely related, probably related, potentially related, unlikely to be related, and not related. Causality will be assessed by the clinician who examines and evaluates the participant based on temporal relationship and their clinical judgment. The Medical Monitor will also provide causal relationship for any Serious Adverse Events (SAEs).
Measured: Day of first dose until 30 days after final day of participation
Number of Participants with Abnormal Laboratory Values as Assessed per NCI-CTCAE v5
Significant changes from participant's baseline established during screening.
Measured: Day of first dose until 30 days after final day of participation
Secondary outcomes (6)
BDTX-1535 Concentration in CSF
BDTX-1535 concentration in CSF will be determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
Measured: Intraoperative
Change in pEGFR Expression in Tumor Tissue
BDTX-1535 treated tumor tissue collected during Phase 0 surgery will be compared to archival tissue (baseline) to determine change in pEGFR expression.
Measured: Baseline and intraoperative
Change in pERK Expression in Tumor Tissue
BDTX-1535 treated tumor tissue collected during Phase 0 surgery will be compared to archival tissue (baseline) to determine change in pERK expression.
Measured: Baseline and intraoperative
6-Month Progression Free Survival (PFS6) Rate
PFS6 rate will be determined in participants who take at least one dose of study treatment.
Measured: From the date of Phase 0 surgery to date of disease recurrence or death, whichever occurs first, assessed up to 12 months after study completion
Median Progression Free Survival (PFS)
Median PFS will be determined in participants with positive PK or PD response.
Measured: From the date of Phase 0 surgery until the date of death due to any cause, assessed for up to 12 months after study completion
Median Overall Survival (OS)
Median OS will be determined in participants with positive PK or PD response.
Measured: From the date of Phase 0 surgery until the date of death due to any cause, assessed for up to 12 months after study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start18 Oct 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Hospital and Medical Center, Phoenix
- Sponsor type
- University, hospital or other
- Collaborators
- Ivy Brain Tumor Center, Barrow Neurological Institute
- Responsible party
- Sponsor
- Investigators
- Nader Sanai, MD, Principal investigator, Chief Scientific Officer/Director of the Ivy Brain Tumor Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06072586
- Sponsor's protocol ID
- 2023-20
- Other IDs
- 24-500-090-34-38
- Status last verified
- Oct 2026
- First submitted
- 25 Sep 2023
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-triggered Expansion Cohort
- ClinicalTrials.gov ID
- NCT06072586
- Acronym / sponsor ID
- 2023-20
- Conditions
- High Grade Glioma, Glioblastoma
- Keywords
- Silevertinib
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 82 participants (estimated)
- Lead sponsor
- St. Joseph's Hospital and Medical Center, PhoenixUniversity, hospital or other
- Collaborators
- Ivy Brain Tumor Center, Barrow Neurological Institute
- Study start
- 18 Oct 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will administer the investigational drug, BDTX-1535 to eligible patients with recurrent high-grade glioma (HGG) and newly-diagnosed glioblastoma (nGBM). 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.
The study design includes a Phase 0 component with PK/PD-trigger for participant enrollment into an Expansion Phase 1 component. The primary objective of the Phase 0 component is to evaluate the PK endpoints of BDTX-1535. The primary objective of the Phase 1 component is to establish the safe dose of BDTX-1535 to be used in participants with a specified treatment regimen, three of which include standard of care radiotherapy for nGBM participants.
Detailed description
The Phase 0 component will include treatment of rHGG (Arms A and B) and nGBM participants (Arms C, D, and E) with BDTX-1535 prior to a planned tumor resection. During surgery, blood, tumor, and CSF samples will be collected to measure the amount of drug that is present in the samples. Arm A includes ascending dose levels with two cohorts, and Arm C includes two dose level cohorts to determine the Optimal Biological Dose (OBD).
The Phase 1 component will include treatment in different dose regimens. Participants with tumors demonstrating PK response (Arms A, B, and C) or PD response (Arms D and E) will continue treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations | Experimental | Drug: BDTX-1535Phase 0: Cohort 1 will receive 200 mg BDTX-1535 once daily (Days 1-5). Cohort 2 will receive 400 mg BDTX-1535 three times over one week (Days 1, 3, and 5). The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. |
| Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion | Experimental | Drug: BDTX-1535Phase 0: Participants will received BDTX-1535 once daily (Days 1-5). The dose level will be determined based on PK results from Arm A, unbound drug concentration in non-enhancing tumor. The final dose will be administered 2-4 hours before tumor resection on Day 5. Phase 1: Participants will received 200 mg BDTX-1535 treatment once daily, continuously in 28-day cycles after surgery. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. |
| Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination) | Experimental | Drug: BDTX-1535 combined with radiation therapyPhase 0: Participants in Cohort 1 will receive 200 mg of BDTX-1535 once daily for 5 days, and participants in Cohort 2 will receive 150 mg of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. . Participants with unmethylated MGMT promoter tumors demonstrating PK response will proceed to the Phase 1 Expansion component. The OBD will be the lowest dose that achieves the following: 9 of 12 participants show PK response and 6 of 12 participants show PD response. Phase 1: Participants with unmethylated MGMT promoter tumors demonstrating a PK response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. |
| Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety) | Experimental | Drug: BDTX-1535 combined with radiation therapyPhase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with unmethylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Arm D: Participants with unmethylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. |
| Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol) | Experimental | Drug: BDTX-1535 combined with temozolomide and radiation therapyPhase 0: Participants will receive the OBD of BDTX-1535 once daily for 5 days. The final dose will be administered 2-4 hours before tumor resection on Day 5. Participants with methylated MGMT promoter tumors demonstrating PD response will proceed to the Phase 1 Expansion component. Phase 1: Participants with methylated MGMT promoter tumors demonstrating a PD response will continue BDTX-1535 treatment at the same dose received during Phase 0, concurrently with standard of care upfront RT and temozolomide (TMZ), followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT. Participants will receive BDTX-1535 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow-up, or study termination by the sponsor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Arms A \& B: Recurrent high grade glioma (2021 WHO Grades 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy.
- Arm C, D, \& E: Newly diagnosed glioblastoma (2021 WHO Grade 4), who have not received any tumor directed intervention other than biopsy or resection.
- Candidate for clinical resection of rHGG (Arms A \& B) or nGBM (Arms C \& D).
- Adequate archival or biopsy tissue available for testing of EGFR alterations. The tissue must have evidence of EGFR alterations including variants, fusion, and mutations with or without amplifications. rHGG participants with EGFR fusion will be solely enrolled into Arm B.
- Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
Key exclusion criteria (10 listed)
- 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 (requiring intravenous [IV] antibiotics or fever >38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening of viral infection is not required for enrollment.
- Significant cardiovascular disease, including NYHA Class III or IV congestive heart failure, myocardial infarction, unstable angina, poorly controlled cardiac arrhythmias, or stroke in the preceding 6 months prior to study Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BDTX-1535Also: SilevertinibBDTX-1535 is an inhibitor of EGFR mutations | Drug | Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations, Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion |
| BDTX-1535 combined with radiation therapyAlso: SilevertinibDuring Phase 1, BDTX-1535 concurrently with standard of care upfront RT, followed by adjuvant monotherapy with BDTX-1535 continuously in 28-day cycles after RT. | Drug | Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination), Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety) |
| BDTX-1535 combined with temozolomide and radiation therapyAlso: SilevertinibDuring Phase 1, BDTX-1535 concurrently with standard of care upfront RT and TMZ, followed by adjuvant BDTX-1535 combined with standard of care TMZ continuously in 28-day cycles after RT. | Drug | Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol) |
Primary outcome
Unbound BDTX-1535 Concentration in Tumor Tissue
Time frame: Intraoperative
Unbound BDTX-1535 concentration in Gd enhancing and Gd non-enhancing tumor tissue will be determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
Total BDTX-1535 Concentration in Tumor Tissue
Time frame: Intraoperative
Total BDTX-1535 concentration in Gd enhancing and Gd non-enhancing tumor tissue will be determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method.
Incidence of DLTs Observed
Time frame: From day of first dose to the end of concurrent RT treatment at 10 weeks
Considered DLTs: Hem toxicity: 8+ days ≥G4 neutropenia/febrile neutropenia; ≥G4, or ≥G3 with clinically significant bleeding, thrombocytopenia; ≥G3 anemia requiring transfusion. Non-hem lab abnormalities: Any AR ≥G3 of ALT/AST or increase in ALT/AST >3x ULN with concurrent increase in total bilirubin >2x ULN (per Hy's Law) in pt with baseline <G1 ALT/AST; Any AR ≥G3 of ALT/AST >2x baseline or 10x ULN in pt with baseline >G2 ALT/AST due to liver mets; Non-hem dose limiting toxicity ≥G3 (per Investigator; except for G3 nausea, vomiting, or diarrhea lasting <72 hrs with adequate antiemetic/supportive care; G3 fatigue or anorexia lasting <1 week; ≥G3 electrolyte abnormality lasting up to 72 hrs, isn't clinically complicated, and resolves spontaneously or responds to intervention). AR requiring dose reduction in C1, causes >2 week delay of C2, causes 8+ day dose interruption in C1. DLTs exclude: alopecia; lymphopenia; isolated lab changes w/o clinical sequelae or significance
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by NCI-CTCAE v5
Time frame: Day of first dose until 30 days after final day of participation
AEs that occur while participants are on study treatment.
Number of Participants with Treatment-Related Adverse Events (TRAEs) as Assessed by NCI-CTCAE v5
Time frame: Day of first dose until 30 days after final day of participation
Causality will be graded using these categories: definitely related, probably related, potentially related, unlikely to be related, and not related. Causality will be assessed by the clinician who examines and evaluates the participant based on temporal relationship and their clinical judgment. The Medical Monitor will also provide causal relationship for any Serious Adverse Events (SAEs).
Number of Participants with Abnormal Laboratory Values as Assessed per NCI-CTCAE v5
Time frame: Day of first dose until 30 days after final day of participation
Significant changes from participant's baseline established during screening.
6 secondary outcomes
BDTX-1535 Concentration in CSF
Time frame: Intraoperative
Change in pEGFR Expression in Tumor Tissue
Time frame: Baseline and intraoperative
Change in pERK Expression in Tumor Tissue
Time frame: Baseline and intraoperative
6-Month Progression Free Survival (PFS6) Rate
Time frame: From the date of Phase 0 surgery to date of disease recurrence or death, whichever occurs first, assessed up to 12 months after study completion
Median Progression Free Survival (PFS)
Time frame: From the date of Phase 0 surgery until the date of death due to any cause, assessed for up to 12 months after study completion
Median Overall Survival (OS)
Time frame: From the date of Phase 0 surgery until the date of death due to any cause, assessed for up to 12 months after study completion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Ivy Brain Tumor Center WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nader Sanai, MD principal investigator
Chief Scientific Officer/Director of the Ivy Brain Tumor Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing BDTX-1535, BDTX-1535 combined with radiation therapy and BDTX-1535 combined with temozolomide and radiation therapy in people with High Grade Glioma and Glioblastoma, run by St. Joseph's Hospital and Medical Center, Phoenix at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Phase 0 Navigator (602-406-8605, research@ivybraintumorcenter.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unbound BDTX-1535 Concentration in Tumor Tissue (time frame: Intraoperative). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.