Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma

Brightline-1: A Phase II/III, Randomized, Open-label, Multi-center Study of Brigimadlin (BI 907828) Compared to Doxorubicin as First Line Treatment of Patients With Advanced Dedifferentiated Liposarcoma

This study is open to people with a type of cancer called dedifferentiated liposarcoma. People with advanced liposarcoma aged 18 or older who are not receiving any other cancer treatment can participate.

The purpose of this study is to compare a medicine called brigimadlin (BI 907828) with doxorubicin in people with liposarcoma. Brigimadlin (BI 907828) is a so-called MDM2 inhibitor that is being developed to treat cancer. Doxorubicin is a medicine already used to treat cancer including liposarcoma.

During the study, participants get either brigimadlin (BI 907828) or doxorubicin. Every 3 weeks, participants take brigimadlin (BI 907828) as tablets or doxorubicin as an infusion into a vein. Participants can switch to brigimadlin (BI 907828) treatment if they did not benefit from doxorubicin treatment.

Participants can continue treatment in the study as long as they benefit from it and can tolerate it.

Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital-Randwick-66496
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Centre Research
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency - Vancouver
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100021
    • Cancer Hospital of Chinese Academy of Medical Science
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Guangzhou, China, 510060
    • Sun yat-sen University Cancer Center
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Affiliated to Fudan University
  • Wuhan, China, 430022
    • Wuhan Union Hospital
• Czechia
  • Brno, Czechia, 65653
    • Masaryk Memorial Cancer Institute
  • Olomouc, Czechia, 77900
    • University Hospital Olomouc
  • Prague, Czechia, 150 06
    • University Hospital Motol
• Denmark
  • Herlev, Denmark, 2730
    • Herlev and Gentofte Hospital
• Finland
  • Helsinki, Finland, 00290
    • HUCH Comprehensive Cancer Center, building 2
  • Tampere, Finland, 33520
    • Tampere University Hospital
• France
  • Bordeaux, France, 33000
    • INS Bergonie
  • Lille, France, 59020
    • CTR Oscar Lambret
  • Lyon, France, 69373
    • CTR Leon Berard
  • Marseille, France, 13385
    • HOP Timone
  • Paris, France, 75014
    • Hopital Cochin
  • Rennes, France, 35042
    • CTR Eugène Marquis
  • Toulouse, France, 31059
    • INS Claudius Regaud IUCT-Oncopole
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Bad Saarow, Germany, 15526
    • Helios Klinikum Bad Saarow
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Dresden, Germany, 01307
    • Technische Universität Dresden
  • Essen, Germany, 45147
    • Universitätsklinikum Essen AöR
  • Hamburg, Germany, 22763
    • Asklepios Kliniken GmbH & Co. KGaA
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Mannheim, Germany, 68167
    • Universitätsklinikum Mannheim GmbH
  • München, Germany, 81377
    • Klinikum der Universität München AÖR
  • Stuttgart, Germany, 70376
    • Robert Bosch Gesellschaft für Medizinische Forschung mbH
• Greece
  • Athens, Greece, 115 27
    • Hippokration General Hospital of Athen
  • Haidari, Greece, 12462
    • "Attikon" University General Hospital of Attica
  • Thessaloniki, Greece, 54622
    • Bioclinic Thessaloniki
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital-Hong Kong-20715
• Italy
  • Bergamo, Italy, 24125
    • Humanitas Gavazzeni
  • Candiolo (TO), Italy, 10060
    • Istituto di Candiolo
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Napoli, Italy, 80131
    • Istituto Nazionale IRCCS Tumori Fondazione Pascale
  • Orbassano (TO), Italy, 10043
    • AOU San Luigi Gonzaga
  • Padua, Italy, 35128
    • Istituto Oncologico Veneto IRCCS
  • Palermo, Italy, 90129
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00128
    • Università Campus Bio-Medico - ROMA
• 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, Chuo-ku, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Koto-ku, Japan, 135-8550
    • Japanese Foundation for Cancer Research
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Nederlands Kanker Instituut
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum (LUMC)
• Norway
  • Oslo, Norway, N-0379
    • Oslo Universitetssykehus HF, Radiumhospitalet
• Portugal
  • Lisbon, Portugal, 1649-035
    • ULS de Santa Maria, E.P.E
  • Lisbon, Portugal, 1099-023
    • IPO Lisboa Francisco Gentil, EPE
• Spain
  • Barcelona, Spain, 08026
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital Duran i Reynals
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico de Santiago
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Lund, Sweden, 22185
    • Skanes universitetssjukhus
  • Stockholm, Sweden, 17177
    • Karolinska Universitetssjukhuset Stockholm
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Abdurrahman Yurtaslan Oncology Training and Research Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • Headington, United Kingdom, OX3 9DS
    • Churchill Hospital
  • London, United Kingdom, NW1 2BU
    • University College Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Chelsea
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona
  • California
    • Beverly Hills, California, United States, 90212
      • Precision NextGen Oncology
    • Duarte, California, United States, 91010
      • City of Hope-Duarte-56419
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Cancer Specialists-Omaha-69502
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College 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.
• Male or female patients ≥18 years old at the time of signature of the informed consent form (ICF). Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial 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.
• Histologically proven locally advanced or metastatic, unresectable (surgery morbidity would outweigh potential benefits), progressive or recurrent dedifferentiated liposarcoma (DDLPS). Locally performed histopathological diagnosis will be accepted for entry into this trial but will be confirmed by independent pathological review while the patients receive treatment in this trial.
• Written pathology report indicating the diagnosis of DDLPS with positive mouse double minute 2 homolog (MDM2) immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization or next generation sequencing (NGS) must be available.
• Formalin fixed paraffin embedded tumor blocks or slides must be available for retrospective histopathological central review.
• Presence of at least one measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least 2 weeks after any biopsy of the target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patient must be willing to donate blood samples for the pharmacokinetics, pharmacodynamics, and tumor mutation analysis.
• Patient willing to undergo a mandatory tumor biopsy at the time point specified in the flowchart unless exempt.
• Adequate organ function.

Exclusion Criteria:

• Known mutation in the TP53 gene (screening for TP53 status is not required).
• Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening.
• Prior systemic therapy for liposarcoma in any setting (including adjuvant, neoadjuvant, maintenance, palliative).
• Previous or concomitant malignancies other than DDLPS or WDLPS, treated within the previous 5 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.
• Previous treatment with anthracyclines in any setting (systemic treatment with other anticancer agents is allowed if completed at least 5 years prior to study entry with the exception of hormone therapy).
• 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.
• Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
• Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant).
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brigimadlin 30 mg q3w; Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 30 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).	Drug: Brigimadlin; Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).; Other Names: BI 907828
Experimental: Brigimadlin 45 mg q3w; Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received 45 milligram (mg) brigimadlin taken orally on day 1 of each 21-day cycle (q3w).	Drug: Brigimadlin; Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).; Other Names: BI 907828
Active Comparator: Doxorubicin; Patients with advanced or metastatic dedifferentiated liposarcoma (DDLPS) received one intravenous infusion of 75 milligram per square meter (mg/m2) on Day 1 of each 21-day cycle (q3w) until a maximum cumulative dose of 450 mg/m2 (approximately 6 cycles).	Drug: Doxorubicin; Intravenous infusion of 75 milligram per square meter (mg/m2) on Day 1 of each 21-day cycle (q3w) until a maximum cumulative dose of 450 mg/m2 (approximately 6 cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival (PFS) based on blinded central independent review. For each patient, PFS was defined as the time interval from randomization until tumor progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (solely based on blinded central independent review) or death from any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter. (Note: the appearance of one or more new lesions is also considered progression).	Up to 20.6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR)	Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 (based on blinded central independent review) from the date of randomization until disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to 20.6 months.
Duration of Objective Response (DOR)	Duration of objective response (DOR), defined as the time interval from first documented confirmed OR until disease progression or death among patients with confirmed OR (based on blinded central independent review), whichever occurs first.	Up to 20.6 months.
Disease Control (DC)	Disease control (DC), defined as a best overall response of CR, PR, or stable disease (SD) according to RECIST version 1.1 (based on blinded central independent review). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Up to 20.6 months.
Change in Health-Related Quality of Life at Week 6 and 18	Mean change from baseline to week 6 and 18 in the following European Organization for Research and Treatment on Cancer (EORTC) Quality of Life Core Questionnaire 30 items (QLQ-C30) scores: Physical functioning (higher score is better); Pain (higher score is worse); Fatigue (higher score is worse); Global health status / QoL (higher score is better) and the following scores obtained using items from the EORTC QLQ-C30 and EORTC Item Library (higher score is worse): Fatigue symptoms; Fatigability; Fatigue impact; Pain descriptors; Pain impact All of the scales and single-item measures range in score from 0 to 100.	Baseline (cycle 1 day 1), week 6 and week 18.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Schoffski P, Lahmar M, Lucarelli A, Maki RG. Brightline-1: phase II/III trial of the MDM2-p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS. Future Oncol. 2023 Mar;19(9):621-629. doi: 10.2217/fon-2022-1291. Epub 2023 Mar 29.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): April 16, 2024
• Study Completion (Actual): January 26, 2026

Study Registration Dates

• First Submitted: January 18, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 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; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Doxorubicin; brigimadlin
• Other Study ID Numbers: 1403-0008; 2021-002392-20 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Once the time frame criteria given under number 4 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