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

Liposarcoma, Dedifferentiated Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06058793
• Other study ID #: 1403-0019
• Secondary ID: 2023-504522-19-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 12, 2023
• Est. completion date: November 30, 2025

Study information

• Verified date: May 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: November 30, 2025
• Est. primary completion date: November 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liposarcoma
• Liposarcoma, Dedifferentiated

Intervention

Drug:
• Brigimadlin
Brigimadlin

Locations

Country	Name	City	State
Argentina	Sanatorio Finochietto	Caba
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Hospital do Cancer de Londrina	Londrina
Brazil	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo André
Brazil	Hospital Sao Domingos	Sao Luis
Brazil	H.S.J. Beneficência Portuguesa - São Paulo	Sao Paulo
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Japan	Aichi Cancer Center Hospital	Aichi, Nagoya
Japan	Nagoya University Hospital	Aichi, Nagoya
Japan	National Cancer Center Hospital East	Chiba, Kashiwa
Japan	Kyushu University Hospital	Fukuoka, Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka, Fukuoka
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Okayama University Hospital	Okayama, Okayama
Japan	Osaka International Cancer Institute	Osaka, Osaka
Japan	Hokkaido Cancer Center	Sapporo, Hokkaido
Japan	Japanese Foundation for Cancer Research	Tokyo, Koto-ku
United Kingdom	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 States	University Cancer and Blood Center	Athens	Georgia
United States	Precision NextGen Oncology	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Northwestern University	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	West Cancer Center & Research Institute	Germantown	Tennessee
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic - Florida	Jacksonville	Florida
United States	Northwell Health	Lake Success	New York
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Kansas Cancer Center	Overland Park	Kansas
United States	Abramson Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic-Arizona	Phoenix	Arizona
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Utah Cancer Specialists Cancer Center	Salt Lake City	Utah
United States	Sarcoma Oncology Center	Santa Monica	California
United States	University of California Los Angeles	Santa Monica	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Medical Oncology Associates, P.S.	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Occurrence of TEAEs with Grade =3 according to CTCAE version 5 during the entire treatment period		up to 23 months
Secondary	Occurrence of treatment-emergent serious adverse events (SAEs)		up to 23 months
Secondary	Occurrence of TEAEs leading to study treatment discontinuation		up to 23 months
Secondary	Occurrence of TEAEs leading to dose reduction		up to 23 months
Secondary	Occurrence of TEAEs leading to dose delay		up to 23 months
Secondary	Occurrence of TEAEs of special interest (adverse events of special interest [AESIs])		up to 23 months
Secondary	Objective response (OR)	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	up to 23 months
Secondary	Progression-free survival (PFS)	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	up to 23 months
Secondary	Overall survival (OS)	OS is defined as the time from treatment start until death from any cause	up to 23 months
Secondary	Duration of objective response (DOR)	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)	up to 23 months
Secondary	Disease control (DC)	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	up to 23 months

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