Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma
- 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
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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
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Male or female patients ≥18 years old at the time of signature of the ICF
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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
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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)
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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)
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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
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Life expectancy ≥3 months at the start of treatment in the opinion of the investigator Further inclusion criteria apply.
- 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 start of study treatment or planned within 6 months after screening
- Previous administration of brigimadlin or any other MDM2-p53 or MDM4 regulator of p53 (MDM4/MDMX)-p53 antagonist
- Previous treatment in study 1403-0008 (Brightline-1)
- Having to receive, or intending to receive, restricted medications or any drug considered likely to interfere with the safe conduct of the study
- Receiving treatment for brain metastases or leptomeningeal disease (LMD) which may interfere with safety and/or endpoint assessment
- Unable to swallow the study treatment
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Brigimadlin treatment Brigimadlin -
- Primary Outcome Measures
Name Time Method Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment period up 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 period up to 23 months
- Secondary Outcome Measures
Name Time Method Occurrence of TEAEs leading to dose reduction up 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 discontinuation up 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 delay up 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