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

Phase 3
Active, not recruiting
Conditions
Liposarcoma, Dedifferentiated
Interventions
Registration Number
NCT06058793
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
240
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.

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Brigimadlin treatmentBrigimadlin-
Primary Outcome Measures
NameTimeMethod
Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment periodup to 23 months
Occurrence of Treatment-emergent adverse events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 during the entire treatment periodup to 23 months
Secondary Outcome Measures
NameTimeMethod
Occurrence of TEAEs leading to dose reductionup to 23 months
Progression-free survival (PFS)up to 23 months

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

Occurrence of treatment-emergent serious adverse events (SAEs)up to 23 months
Occurrence of TEAEs leading to study treatment discontinuationup to 23 months
Occurrence of TEAEs of special interest (adverse events of special interest [AESIs])up to 23 months
Objective response (OR)up to 23 months

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, or last evaluable tumour assessment before start of subsequent anticancer therapy, lost to follow-up, or withdrawal of consent

Duration of objective response (DOR)up to 23 months

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)

Disease control (DC)up to 23 months

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

Occurrence of TEAEs leading to dose delayup to 23 months
Overall survival (OS)up to 23 months

OS is defined as the time from treatment start until death from any cause

Trial Locations

Locations (61)

National Cancer Center Hospital

🇯🇵

Tokyo, Chuo-ku, Japan

Precision NextGen Oncology

🇺🇸

Beverly Hills, California, United States

Sarcoma Oncology Center

🇺🇸

Santa Monica, California, United States

Mayo Clinic - Florida

🇺🇸

Jacksonville, Florida, United States

University Cancer and Blood Center

🇺🇸

Athens, Georgia, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Tohoku University Hospital

🇯🇵

Miyagi, Sendai, Japan

Okayama University Hospital

🇯🇵

Okayama, Okayama, Japan

Istituto Oncologico Veneto IRCCS

🇮🇹

Padova, Italy

A.O. Univ. Policlinico Giaccone

🇮🇹

Palermo, Italy

Università Campus Bio-Medico - ROMA

🇮🇹

Roma, Italy

AO Città della Salute e Scienza

🇮🇹

Torino, Italy

University of Arizona

🇺🇸

Tucson, Arizona, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

M Health Fairview University of Minnesota Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Prince of Wales Hospital-Randwick-66496

🇦🇺

Randwick, New South Wales, Australia

UZ Leuven

🇧🇪

Leuven, Belgium

OncoClinicas Rio de Janeiro

🇧🇷

Rio de Janeiro, Brazil

ICESP - Instituto do Cancer do Estado de Sao Paulo

🇧🇷

Sao Paulo, Brazil

A.C. Camargo

🇧🇷

Sao Paulo, Brazil

Arthur J. E. Child Comprehensive Cancer Centre

🇨🇦

Calgary, Alberta, Canada

BC Cancer Agency - Vancouver Island Centre

🇨🇦

Victoria, British Columbia, Canada

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Istituto Nazionale IRCCS Tumori Fondazione Pascale

🇮🇹

Napoli, Italy

AOU San Luigi Gonzaga

🇮🇹

Orbassano (TO), Italy

University of Kansas Cancer Center

🇺🇸

Overland Park, Kansas, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Nebraska Methodist Hospital

🇺🇸

Omaha, Nebraska, United States

Northwell Health

🇺🇸

Lake Success, New York, United States

Abramson Cancer Center at Pennsylvania Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

West Cancer Center & Research Institute

🇺🇸

Germantown, Tennessee, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Utah Cancer Specialists Cancer Center

🇺🇸

Salt Lake City, Utah, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

Fred Hutchinson Cancer Research Center

🇺🇸

Seattle, Washington, United States

Froedtert and The Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Sanatorio Finochietto

🇦🇷

Caba, Argentina

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Sir Charles Gairdner Hospital

🇦🇺

Nedlands, Western Australia, Australia

Hospital do Cancer de Londrina

🇧🇷

Londrina, Brazil

CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia

🇧🇷

Santo André, Brazil

H.S.J. Beneficência Portuguesa - São Paulo

🇧🇷

Sao Paulo, Brazil

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Aichi Cancer Center Hospital

🇯🇵

Aichi, Nagoya, Japan

Nagoya University Hospital

🇯🇵

Aichi, Nagoya, Japan

National Cancer Center Hospital East

🇯🇵

Chiba, Kashiwa, Japan

National Hospital Organization Kyushu Cancer Center

🇯🇵

Fukuoka, Fukuoka, Japan

Kyushu University Hospital

🇯🇵

Fukuoka, Fukuoka, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Osaka, Japan

Hokkaido Cancer Center

🇯🇵

Sapporo, Hokkaido, Japan

Japanese Foundation for Cancer Research

🇯🇵

Tokyo, Koto-ku, Japan

Addenbrooke's Hospital

🇬🇧

Cambridge, United Kingdom

Beatson West of Scotland Cancer Centre

🇬🇧

Glasgow, United Kingdom

The Royal Marsden Hospital, Chelsea

🇬🇧

London, United Kingdom

The Christie Hospital

🇬🇧

Manchester, United Kingdom

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