Clinical trial NCT06058793: Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Liposarcoma, Dedifferentiated
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of Treatment-emergent adverse events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 during the entire treatment period
timeFrame: up to 23 months
measure: Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment period
timeFrame: up to 23 months
Secondary outcomes:
measure: Occurrence of treatment-emergent serious adverse events (SAEs)
timeFrame: up to 23 months
measure: Occurrence of TEAEs leading to study treatment discontinuation
timeFrame: up to 23 months
measure: Occurrence of TEAEs leading to dose reduction
timeFrame: up to 23 months
measure: Occurrence of TEAEs leading to dose delay
timeFrame: up to 23 months
measure: Occurrence of TEAEs of special interest (adverse events of special interest [AESIs])
timeFrame: up to 23 months
measure: Objective response (OR)
timeFrame: up to 23 months
measure: Progression-free survival (PFS)
timeFrame: up to 23 months
measure: Overall survival (OS)
timeFrame: up to 23 months
measure: Duration of objective response (DOR)
timeFrame: up to 23 months
measure: Disease control (DC)
timeFrame: up to 23 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic-Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic - Florida
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Overland Park
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Abramson Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center & Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates, P.S.
state: Washington
city: Milwaukee
country: United States
facility: Froedtert and The Medical College of Wisconsin
state: Wisconsin
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Caba
country: Argentina
facility: Sanatorio Finochietto
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: Randwick
country: Australia
facility: Prince of Wales Hospital-Randwick-66496
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Fortaleza
country: Brazil
facility: Pronutrir
city: Londrina
country: Brazil
facility: Hospital do Cancer de Londrina
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
city: Sao Luis
country: Brazil
facility: Hospital Sao Domingos
city: Sao Paulo
country: Brazil
facility: H.S.J. Beneficência Portuguesa - São Paulo
city: Calgary
country: Canada
facility: Arthur J. E. Child Comprehensive Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Aichi, Nagoya
country: Japan
facility: Nagoya University Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka, Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka, Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Sapporo, Hokkaido
country: Japan
facility: Hokkaido Cancer Center
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: The Royal Marsden Hospital, Chelsea
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
References: