Brightline-4: A study to test how well brigimadlin is tolerated by people with a type of cancer called dedifferentiated liposarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 12 Dec 2025

Decision date (initial)

2024-05-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504522-19-00

WHO UTN

U1111-1291-7646

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

The primary objective of the study is to evaluate the safety of brigimadlin in patients with advanced or metastatic DDLPS by assessing the incidence of treatment-emergent adverse events (TEAEs) and to characterise the severity, frequency, seriousness, relationship, and outcome of TEAEs. Intercurrent event handling strategies will be applied.

Secondary objectives 1

1. The secondary objective is to evaluate efficacy by using objective response (OR), duration of objective response (DOR), PFS, and OS, and to further assess safety.

Conditions and MedDRA coding

dedifferentiated liposarcoma

Study design 3 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003260-PIP01-22

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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)1 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 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
9. Further criteria apply.

Exclusion criteria 9

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
9. Further criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Occurrence of TEAEs according to CTCAE version 5 during the entire treatment period
2. Occurrence of TEAEs with Grade ≥3 according to CTCAE version 5 during the entire treatment period

Secondary endpoints 10

1. Occurrence of treatment-emergent serious adverse events (SAEs)
2. Occurrence of TEAEs leading to study treatment discontinuation
3. Occurrence of TEAEs leading to dose reduction
4. Occurrence of TEAEs leading to dose delay
5. Occurrence of TEAEs of special interest (adverse events of special interest [AESIs])
6. Objective response: OR is defined as a best overall response of confirmed complete response (CR) or confirmed 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
7. Progression-free survival: 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
8. Overall survival: OS is defined as the time from treatment start until death from any cause
9. Duration of objective response: 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)
10. Disease control (DC): DC is defined as a best overall response of CR, PR, or SD where best overall response is defined according to RECIST version 1.1 based on investigator assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications