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

• ClinicalTrials.gov Identifier: NCT06072586
• Recruitment Status: Recruiting
• First Posted: October 10, 2023
• Last Update Posted: November 28, 2023
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: Ivy Brain Tumor Center; Barrow Neurological Institute
• Information provided by (Responsible Party): St. Joseph's Hospital and Medical Center, Phoenix

Tracking Information

• First Submitted Date: September 25, 2023
• First Posted Date: October 10, 2023
• Last Update Posted Date: November 28, 2023
• Actual Study Start Date: October 18, 2023
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2023)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 2, 2023)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions
• Official Title: 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
• 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.
• 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 Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: High Grade Glioma

Intervention

Drug: BDTX-1535

BDTX-1535 is an inhibitor of EGFR mutations

Study Arms

• Experimental: Recurrent high-grade glioma participants with EGFR alterations
  Intervention: Drug: BDTX-1535
• Experimental: Recurrent high-grade glioma participants with EGFR fusion
  Intervention: Drug: BDTX-1535

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 2, 2023): 22
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2025
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility 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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Phase 0 Navigator; 602-406-8605; research@ivybraintumorcenter.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06072586
• Other Study ID Numbers: 2023-20; 24-500-090-34-38 ( Other Identifier: SJHMC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: St. Joseph's Hospital and Medical Center, Phoenix
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Original Study Sponsor: Same as current

Collaborators

• Ivy Brain Tumor Center
• Barrow Neurological Institute

Investigators

• Principal Investigator: Nader Sanai, MD; Chief Scientific Officer/Director of the Ivy Brain Tumor Center

• PRS Account: St. Joseph's Hospital and Medical Center, Phoenix
• Verification Date: November 2023