This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)

A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study of BI 907828 (Brigimadlin) in Patients With Advanced or Metastatic Solid Tumors

This study is open to adults with different types of advanced cancer (solid tumors). The purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the participants can tolerate. The most suitable dose is used in the second part to find out whether brigimadlin makes tumors shrink.

In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet. Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every 4 weeks.

The participants are in the study for as long as they benefit from and can tolerate treatment. The doctors regularly check the participants' general health during the study.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BI 907828

• Study Type: Interventional
• Enrollment (Actual): 266
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet, København
• Germany
  • Berlin, Germany, 13125
    • HELIOS Klinikum Berlin-Buch
  • Cologne, Germany, 50937
    • Universitätsklinikum Köln (AöR)
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen, Georg-August-Universität
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Israel
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center
• Japan
  • Tokyo, Chuo-ku, Japan, 104-0045
    • National Cancer Center Hospital
• Poland
  • Poznan, Poland, 60-693
    • MED POLONIA SP Z O O, Clinical Trials Department,Poznan
  • Warsaw, Poland, 02-781
    • Oncology Center-Maria Sklodowska-Curie Institute
• South Korea
  • Seoul, South Korea, 03722
    • Severance Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico de Santiago
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska Comprehensive Cancer Center
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists-Sarasota-61670
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute, Downtown
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Pathologically documented, advanced solid tumors.

• Patients fulfilling one or more of the following criteria:

  • Radiologically documented disease progression or relapse
  • Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist.
  • Patients with MDM2 amplified sarcomas who require first line treatment (for Ph Ib/dose expansion - Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status, and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any line of therapy. If TP53 status is not available during screening, the patient may be included with unknown TP53 status if a tissue sample is submitted for central laboratory assessment. If TP53 status cannot be evaluated, the patient may be included if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract (including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.
• Phase Ib (expansion phase) only:
• At least one target lesion that can be accurately measured per RECIST v.1.1.
• Phase Ia:
• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker, and PGx analyses.
• Phase Ib:
• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses and blood sampling for PK, pharmacodynamics, and biomarker analyses.
• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen, collected before screening within 12 months of enrollment, may be submitted. If these requirements cannot be met, then the patient may be allowed to enter the study at Sponsor discretion, after agreement between the Investigator and Sponsor.
• Further inclusion criteria apply

Exclusion Criteria:

• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated brain metastases may participate provided they are stable, without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or computed tomography (CT) scan), for at least four weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline; have no evidence of new or enlarging brain metastases. Patients on corticosteroids must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to start of study treatment, or planned within 12 months after screening (e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation	Drug: BI 907828; Film-coated tablet; Other Names: brigimadlin
Experimental: Dose Expansion	Drug: BI 907828; Film-coated tablet; Other Names: brigimadlin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase Ia- Maximum tolerated dose (MTD) based on number of patients with dose limiting toxicities (DLTs) during first treatment cycle	Up to 28 days
Phase Ib - Progression-free survival	Up to 24 months
Phase Ia - Number of patients with DLTs during first treatment cycle (21 days, Arm A; 28 days, Arm B)	Up to 28 days
Phase Ib - Number of patients with DLTs during the first treatment cycle	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase Ia - Cmax: Maximum measured concentration of BI 907828 in plasma	Up to 24 months
Phase Ia - AUC0-∞: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity	Up to 24 months
Phase Ib - Objective response	Up to 24 months
Phase Ib - Overall survival	Up to 24 months
Phase Ib - Number of patients with Grade ≥3 treatment-related adverse events observed during the entire treatment period	Up to 24 months
Phase Ib - Cmax: Maximum measured concentration of BI 907828 in plasma	Up to 24 months
Phase Ib - AUC0-∞: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity	Up to 24 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• LoRusso P, Yamamoto N, Patel MR, Laurie SA, Bauer TM, Geng J, Davenport T, Teufel M, Li J, Lahmar M, Gounder MM. The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study. Cancer Discov. 2023 Aug 4;13(8):1802-1813. doi: 10.1158/2159-8290.CD-23-0153.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): November 13, 2025
• Study Completion (Actual): November 13, 2025

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; brigimadlin
• Other Study ID Numbers: 1403-0001; 2017-003210-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• IPD Sharing Access Criteria: For study documents - upon signing of a "Document Sharing Agreement". For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No