Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma

Brightline-4: A Phase III Open-label, Single-arm, Multi-center Study to Assess the Safety and Efficacy of Brigimadlin (BI 907828) Treatment in Patients With Treatment-naïve or Pre-treated Advanced Dedifferentiated Liposarcoma

This study is open to adults with a type of cancer called dedifferentiated liposarcoma (DDLPS). They can join the study if their tumours are positive for MDM2. The purpose of this study is to find out whether a medicine called brigimadlin (BI 907828) is tolerated by and helps people with DDLPS. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer.

Participants take brigimadlin as a tablet once every 3 weeks. Participants may continue to take brigimadlin as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check participants' health and take note of any unwanted effects. The doctors also regularly check tumour size.

Study Overview

• Status: Completed
• Conditions: Liposarcoma, Dedifferentiated
• Intervention / Treatment: Drug: Brigimadlin

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • CABA, Argentina, 1280AEB
    • Hospital Britanico de Buenos Aires
  • CABA, Argentina, C1120AAB
    • Sanatorio Finochietto
  • Ciudad Autonoma de Bs As, Argentina, C1426ANZ
    • Instituto Médico Especializado Alexander Fleming
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital-Randwick-66496
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Brazil
  • Fortaleza, Brazil, 60810-180
    • Pronutrir
  • Londrina, Brazil, 86015-520
    • Hospital do Câncer de Londrina
  • Santo André, Brazil, 09060-650
    • CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
  • São Luís, Brazil, 65060-645
    • Hospital Sao Domingos
  • São Paulo, Brazil, 01323-001
    • H.S.J. Beneficência Portuguesa - São Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J. E. Child Comprehensive Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre (MUHC)
• Japan
  • Aichi, Nagoya, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Aichi, Nagoya, Japan, 466-8560
    • Nagoya University Hospital
  • Chiba, Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East
  • Fukuoka, Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Fukuoka, Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Miyagi, Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Okayama, Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Sapporo, Hokkaido, Japan, 003-0804
    • Hokkaido Cancer Center
  • Tokyo, Koto-ku, Japan, 135-8550
    • Japanese Foundation for Cancer Research
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Chelsea
  • Manchester, United Kingdom, M20 4BX
    • The Christie
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic-Arizona
  • California
    • Beverly Hills, California, United States, 90212
      • Precision NextGen Oncology
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Florida
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Abramson Cancer Center at Pennsylvania Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center & Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, P.S.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated, written informed consent form (ICF) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any study-specific procedures, sampling, or analyses
2. Male or female patients ≥18 years old at the time of signature of the ICF
3. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use two medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of <1% per year when used consistently and correctly beginning at screening, during study participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information

4. Histologically documented locally advanced or metastatic, unresectable (i.e. surgery morbidity would outweigh potential benefits), progressive or recurrent Dedifferentiated liposarcoma (DDLPS), meeting the criteria for an open study cohort:

   • Cohort A: patient has not received prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
   • Cohort B: patient has received any prior systemic therapy for DDLPS in any setting (including adjuvant, neoadjuvant, maintenance, palliative)
5. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridisation (FISH) or next-generation sequencing (NGS)
6. Presence of at least 1 measurable target lesion according to RECIST version 1.1. In patients who only have 1 target lesion, the baseline imaging must be performed at least 2 weeks after any biopsy of the target lesion
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Life expectancy ≥3 months at the start of treatment in the opinion of the investigator Further inclusion criteria apply.

Exclusion Criteria:

1. Known mutation in the TP53 gene (screening for TP53 status is not required)
2. Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to start of study treatment or planned within 6 months after screening
3. Previous administration of brigimadlin or any other MDM2-p53 or MDM4 regulator of p53 (MDM4/MDMX)-p53 antagonist
4. Previous treatment in study 1403-0008 (Brightline-1)
5. Having to receive, or intending to receive, restricted medications or any drug considered likely to interfere with the safe conduct of the study
6. Receiving treatment for brain metastases or leptomeningeal disease (LMD) which may interfere with safety and/or endpoint assessment
7. Unable to swallow the study treatment
8. Previous or concomitant malignancies other than the one treated in this study within the previous 2 years, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ, or other malignancy that is considered cured by local treatment Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brigimadlin treatment	Drug: Brigimadlin; Brigimadlin; Other Names: BI 907828

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of Treatment-emergent adverse events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 during the entire treatment period	up to 23 months
Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment period	up to 23 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment-emergent serious adverse events (SAEs)		up to 23 months
Occurrence of TEAEs leading to study treatment discontinuation		up to 23 months
Occurrence of TEAEs leading to dose reduction		up to 23 months
Occurrence of TEAEs leading to dose delay		up to 23 months
Occurrence of TEAEs of special interest (adverse events of special interest [AESIs])		up to 23 months
Progression-free survival (PFS)	PFS is defined as the time from treatment start until the earliest date of tumour progression according to RECIST version 1.1, based on investigator assessment, or death from any cause	up to 23 months
Overall survival (OS)	OS is defined as the time from treatment start until death from any cause	up to 23 months
Duration of objective response (DOR)	DOR is defined as the time from first documented confirmed OR until the earliest date of disease progression or death among patients with confirmed OR (based on investigator assessment)	up to 23 months
Disease control (DC)	DC is defined as a best overall response of CR, PR, or stable disease (SD) where best overall response is defined according to RECIST version 1.1 based on investigator assessment	up to 23 months
Objective response (OR)	OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (based on investigator assessment) from the date of treatment start until the earliest date of disease progression, death, last evaluable tumour assessment before start of subsequent anticancer therapy, lost to follow-up, withdrawal of consent or end of study (EoS)	up to 23 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Actual): December 12, 2025
• Study Completion (Actual): December 12, 2025

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Adipose Tissue; Liposarcoma; brigimadlin
• Other Study ID Numbers: 1403-0019; 2023-504522-19-00 (Registry Identifier: CTIS)

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.mystudywindow.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: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• 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