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

Part of paid clinical trials in Chandler, Arizona.

Sponsor
St. Joseph's Hospital and Medical Center, Phoenix
Study ID
NCT06072586
Phase
EARLY_PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • BDTX-1535 — DRUG
    BDTX-1535 is an inhibitor of EGFR mutations
  • BDTX-1535 combined with radiation therapy — 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.
  • BDTX-1535 combined with temozolomide and radiation therapy — 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.

Study Details

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.

Key Dates

Start date
Oct 18, 2023
Status verified
Sep 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2027

Study Design

Enrollment
82 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Unbound BDTX-1535 Concentration in Tumor Tissue [ Time Frame: Intraoperative ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Chandler Regional Medical CenterChandlerArizona85224
Annette Taylor, RN
[email protected]
480-728-5721
Kaith Almefty, MD (PRINCIPAL_INVESTIGATOR)
St. Joseph's Hospital and Medical CenterPhoenixArizona85013
Phase 0 Navigator
[email protected]
602-406-8605
Nader Sanai, MD (PRINCIPAL_INVESTIGATOR)

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Chandler Regional Medical Center· Chandler, AZSt. Joseph's Hospital and Medical Center· Phoenix, AZ

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