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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Liposarcoma, Dedifferentiated

Intervention / Treatment
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* Drug: Brigimadlin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Male or female patients ≥18 years old at the time of signature of the ICF 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 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) 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) 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy ≥3 months at the start of treatment in the opinion of the investigator Further inclusion criteria apply. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brigimadlin treatment<br> | Drug: Brigimadlin<br>* Brigimadlin<br>* Other names: BI 907828;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment period |  | up to 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 leading to dose reduction |  | up to 23 months | 
| Occurrence of TEAEs leading to dose delay |  | up to 23 months | 
| Occurrence of TEAEs of special interest (adverse events of special interest [AESIs]) |  | up to 23 months | 
| 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 | 
| 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 | 
| Overall survival (OS) | OS is defined as the time from treatment start until death from any cause | up to 23 months | 
| 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 | 
| 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 |