A Study to Determine How BI 907828 (Brigimadlin) is Taken up in the Tumor (Phase 0) and to Determine the Highest Dose of BI 907828 (Brigimadlin) That Could be Tolerated (Phase 1a) in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma

NCT05376800 | Completed Phase 1 FDA Drug

• 3 other identifiers: 1403-00072023-506409-20-002021-005737-17
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 7

Brief Summary

This study is open to adults with newly diagnosed glioblastoma, a type of brain tumor. The study has two parts. Part 1 is open to people who can get their brain tumor removed by surgery. Part 2 is open to people who already had such a brain surgery. This study tests a medicine called BI 907828 (Brigimadlin). BI 907828 (Brigimadlin) is a socalled MDM2 inhibitor that is being developed to treat cancer. The purpose of Part 1 of the study is to find out how BI 907828 (Brigimadlin) is taken up in the tumor. Participants take a single dose of BI 907828 (Brigimadlin) as a tablet before the brain surgery. Part 1 of the study takes about 1 month. During this time, participants have their brain tumor removed by surgery and visit the study site about 8 times. The purpose of Part 2 is to find the highest dose of BI 907828 (Brigimadlin) that the participants can tolerate in combination with standard radiation therapy. During the first 6 weeks, participants get standard radiation therapy. In addition, they take a dose of BI 907828 (Brigimadlin) once every 3 weeks. Participants may continue to take BI 907828 (Brigimadlin) as long as they benefit from treatment and can tolerate it. They visit the study site regularly. During the entire study, doctors also regularly check participants' health and take note of any unwanted effects.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (4)

• Phase 0: Measured total concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions

  Brain tissue samples will be collected after standard of care neurosurgical tumor resection. Concentration of BI 907828 (Brigimadlin) will be quantitated in nanomole/kilogram (nmol/Kg) of tissue by validated liquid chromatography mass spectrometry (LC/MS) method.

  Up to 24 hours (h)

• Phase 0: Calculated unbound concentration of BI 907828 (Brigimadlin) in brain tissue homogenate from noncontrast enhancing and contrast enhancing brain tumor regions

  Brain tissue samples will be collected after standard of care neurosurgical tumor resection. Concentration of BI 907828 (Brigimadlin) will be quantitated in nanomole/kilogram (nmol/Kg) of tissue by validated liquid chromatography mass spectrometry (LC/MS) method.

  Up to 24 hours (h)

• Phase Ia: Occurrence of dose-limiting toxicity (DLT), graded according to Common Terminology Criteria for Adverse Events version 5.0, during the Maximum Tolerated Dose (MTD) evaluation period

  Up to 63 Days

• Phase Ia: Occurrence of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 during the entire treatment period

  Up to 7 months.

Secondary Outcomes (5)

• Phase 0: Dose-dependent changes of expression levels of Tumor suppressor protein p53 (TP53) target genes in contrast enhancing brain regions and non-contrast enhancing brain regions

  Up to 24 hours (h)

• Phase Ia: Progression-free survival (PFS)

  Up to 8 months.

• Phase Ia: Maximum plasma concentration (Cmax) of BI 907828 (Brigimadlin) in plasma at Cycle 1

  Up to Day 17

• Phase Ia: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)

  Up to Day 17

• Phase Ia: Area under the Curve of BI 907828 (Brigimadlin) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)

  Up to Day 17

Study Arms (2)

Phase 0 Part: BI 907828 (Brigimadlin)

EXPERIMENTAL

Drug: BI 907828 (Brigimadlin)

Phase Ia Part: BI 907828 (Brigimadlin)

EXPERIMENTAL

Drug: BI 907828 (Brigimadlin)

Interventions

BI 907828 (Brigimadlin) DRUG

BI 907828 (Brigimadlin)

Also known as: Brigimadlin

Phase 0 Part: BI 907828 (Brigimadlin); Phase Ia Part: BI 907828 (Brigimadlin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically (if prior biopsy) or radiologically diagnosed glioblastoma.
• Neurosurgical tumor resection is indicated and planned according to the assessment of the treating physician.
• Patients must be at least 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (an ECOG of 2 is acceptable, if it is due to non-cancer-related disability, and after agreement with the sponsor).
• Histologically demonstrated diagnosis of TP53 wild type glioblastoma harboring unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoters. Glioblastoma definition according to 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) tumors, i.e. IDH- wild type only.
• Patient has undergone neurosurgical tumor resection and is eligible for standard radiotherapy.
• For patients, who have participated in Phase 0, the interval between the single dose of BI 907828 (Brigimadlin) and subsequent Phase 1a treatment must be at least 21 days.

You may not qualify if:

• Patient who must receive or intends to receive restricted medications.
• Patients with pacemakers or other metallic implants that can interfere with the magnetic field during Magnetic Resonance Imaging (MRI) investigations.
• Inability to undergo contrast-enhanced MRI (Glomerular Filtration Rate (GFR) \<30 mL/min).
• Patients who have received previous systemic therapy (with the exception of patients who participated in Phase 0) or radiotherapy for glioblastoma.
• Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Patients with pacemakers or other metallic implants that can interfere with the magnetic field during MRI investigations.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (7)

Mayo Clinic-Arizona

Phoenix, Arizona, 85054, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Glioblastoma

Interventions

brigimadlin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 0 part: measurement of BI 907828 (Brigimadlin) concentrations in brain tissue Phase Ia part: dose escalation

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 17, 2022
• Study Start: November 30, 2022
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); BE (1); ES (2)