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

NCT ID: NCT06072586

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-18
• Study Completion Date: 2027-12-31

Brief 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. 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.

Conditions

High Grade Glioma; Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Recurrent High-Grade Glioma Participants with EGFR Alterations

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.

Group Type: EXPERIMENTAL

BDTX-1535

Intervention Type: DRUG

BDTX-1535 is an inhibitor of EGFR mutations

Arm B: Recurrent High-Grade Glioma Participants with EGFR Fusion

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.

Group Type: EXPERIMENTAL

BDTX-1535

Intervention Type: DRUG

BDTX-1535 is an inhibitor of EGFR mutations

Arm C: Newly-Diagnosed GBM Participants with EGFR Alterations (OBD Determination)

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.

Group Type: EXPERIMENTAL

BDTX-1535 combined with radiation therapy

Intervention Type: DRUG

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.

Arm D: Newly-Diagnosed GBM Participants with EGFR Alterations (BDTX-1535 + RT Safety)

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.

Group Type: EXPERIMENTAL

BDTX-1535 combined with radiation therapy

Intervention Type: DRUG

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.

Arm E: Newly-Diagnosed GBM Participants with EGFR Alterations (Stupp protocol)

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.

Group Type: EXPERIMENTAL

BDTX-1535 combined with temozolomide and radiation therapy

Intervention Type: DRUG

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.

Interventions

BDTX-1535

BDTX-1535 is an inhibitor of EGFR mutations

Intervention Type: DRUG

BDTX-1535 combined with radiation therapy

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.

Intervention Type: DRUG

BDTX-1535 combined with temozolomide and radiation therapy

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

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 (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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ivy Brain Tumor Center

OTHER

Sponsor Role: collaborator

Barrow Neurological Institute

OTHER

Sponsor Role: collaborator

St. Joseph's Hospital and Medical Center, Phoenix

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nader Sanai, MD

Role: PRINCIPAL_INVESTIGATOR

Chief Scientific Officer/Director of the Ivy Brain Tumor Center

Locations

Chandler Regional Medical Center

Chandler, Arizona, United States

Site Status: RECRUITING

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Phase 0 Navigator

Role: CONTACT

research@ivybraintumorcenter.org

602-406-8605

Facility Contacts

Annette Taylor, RN

Role: primary

annette.taylor3@commonspirit.org

480-728-5721

Phase 0 Navigator

Role: primary

research@ivybraintumorcenter.org

602-406-8605

Related Links

http://www.ivybraintumorcenter.org/

Ivy Brain Tumor Center Website

Other Identifiers

24-500-090-34-38

Identifier Type: OTHER

Identifier Source: secondary_id

2023-20

Identifier Type: -

Identifier Source: org_study_id