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

NCT05218499 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1403-00082021-002392-20
• Study Type: interventional
• Target: 400
• Locations: 22 countries
• Sites: 109

Brief Summary

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.

Conditions

Liposarcoma, Dedifferentiated

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Objective Response (OR)

  Up to 20.6 months.

• Duration of Objective Response (DOR)

  Up to 20.6 months.

• Disease Control (DC)

  Up to 20.6 months.

• Change in Health-Related Quality of Life at Week 6 and 18

  Baseline (cycle 1 day 1), week 6 and week 18.

Study Arms (3)

Brigimadlin 30 mg q3w

EXPERIMENTAL

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 45 mg q3w

EXPERIMENTAL

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

Doxorubicin

ACTIVE COMPARATOR

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

Interventions

Brigimadlin DRUG

Brigimadlin taken orally on day 1 of each 21-day cycle (q3w).

Also known as: BI 907828

Brigimadlin 30 mg q3w; Brigimadlin 45 mg q3w

Doxorubicin DRUG

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).

Doxorubicin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (109)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Arizona

Tucson, Arizona, 85719, United States

Location

Precision NextGen Oncology

Beverly Hills, California, 90212, United States

Location

City of Hope-Duarte-56419

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists-Omaha-69502

Omaha, Nebraska, 68114, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Prince of Wales Hospital-Randwick-66496

Randwick, New South Wales, 2031, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

BC Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Cancer Hospital of Chinese Academy of Medical Science

Beijing, 100021, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, 510060, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Zhongshan Hospital Affiliated to Fudan University

Shanghai, 200032, China

Location

Wuhan Union Hospital

Wuhan, 430022, China

Location

Masaryk Memorial Cancer Institute

Brno, 65653, Czechia

Location

University Hospital Olomouc

Olomouc, 77900, Czechia

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

HUCH Comprehensive Cancer Center, building 2

Helsinki, 00290, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

INS Bergonie

Bordeaux, 33000, France

Location

CTR Oscar Lambret

Lille, 59020, France

Location

CTR Leon Berard

Lyon, 69373, France

Location

HOP Timone

Marseille, 13385, France

Location

Hôpital Cochin

Paris, 75014, France

Location

CTR Eugène Marquis

Rennes, 35042, France

Location

INS Claudius Regaud IUCT-Oncopole

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Technische Universität Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Essen AöR

Essen, 45147, Germany

Location

Asklepios Kliniken GmbH & Co. KGaA

Hamburg, 22763, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Mannheim GmbH

Mannheim, 68167, Germany

Location

Klinikum der Universität München AÖR

München, 81377, Germany

Location

Robert Bosch Gesellschaft für medizinische Forschung mbH

Stuttgart, 70376, Germany

Location

Hippokration General Hospital of Athen

Athens, 115 27, Greece

Location

"Attikon" University General Hospital of Attica

Haidari, 12462, Greece

Location

Bioclinic Thessaloniki

Thessaloniki, 54622, Greece

Location

Prince of Wales Hospital-Hong Kong-20715

Hong Kong, Hong Kong

Location

Humanitas Gavazzeni

Bergamo, 24125, Italy

Location

Istituto Di Candiolo

Candiolo (TO), 10060, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Naples, 80131, Italy

Location

AOU San Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90129, Italy

Location

Università Campus Bio-Medico - ROMA

Roma, 00128, Italy

Location

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681, Japan

Location

Nagoya University Hospital

Aichi, Nagoya, 466-8560, Japan

Location

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Tohoku University Hospital

Miyagi, Sendai, 980-8574, Japan

Location

Okayama University Hospital

Okayama, Okayama, 700-8558, Japan

Location

Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan

Location

Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

Location

Nederlands Kanker Instituut

Amsterdam, 1066 CX, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

Location

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, N-0379, Norway

Location

IPO Lisboa Francisco Gentil, EPE

Lisbon, 1099-023, Portugal

Location

ULS de Santa Maria, E.P.E

Lisbon, 1649-035, Portugal

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08026, Spain

Location

Hospital Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Skånes universitetssjukhus

Lund, 22185, Sweden

Location

Karolinska Universitetssjukhuset Stockholm

Stockholm, 17177, Sweden

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

Churchill Hospital

Headington, OX3 9DS, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

The Royal Marsden Hospital, Chelsea

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36987836 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Liposarcoma

Interventions

brigimadlin; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 1, 2022
• Study Start: March 31, 2022
• Primary Completion: April 16, 2024
• Study Completion: January 26, 2026
• Last Updated: March 2, 2026
• Results First Posted: July 4, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

CN (9); HK (1); ES (10); US (20); GB (5); TU (1); CA (4); DE (9); FR (8); BE (1); PT (2); NO (1); DK (1); GR (3); JP (11); CZ (3); SE (2); AU (4); IT (8); TW (2); NL (2); FI (2)