Brightline-3: A Study to Find Out Whether Brigimadlin in Combination With Ezabenlimab Helps People With Advanced Soft Tissue Sarcoma

NCT06370871 | Withdrawn Phase 3 DMC FDA Drug

• 3 other identifiers: 1403-00062022-502985-26-00U1111-1292-9594
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is open to adults with specific types of advanced soft tissue sarcoma. People with undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) can join the study if they have a normal version of the TP53 gene. This is a study for people whose earlier treatment isn't working anymore, and their doctors suggest a new treatment to stop the sarcoma from getting worse. The purpose of this study is to compare a medicine called brigimadlin in combination with another medicine called ezabenlimab with chemotherapy. Brigimadlin is a so-called MDM2-p53 antagonist that is being developed to treat cancer. Ezabenlimab is an antibody that may help the immune system fight cancer. Participants are put into 3 groups by chance:

• Ezabenlimab group: Participants receive ezabenlimab as an infusion into a vein every 3 weeks
• Brigimadlin + ezabenlimab group: Participants take brigimadlin as tablets and receive ezabenlimab as an infusion into a vein every 3 weeks
• Chemotherapy group: Participants get chemotherapy as an infusion into a vein on 2 days every 3 weeks. Chemotherapy is a combination of gemcitabine and docetaxel which is often used in the treatment of sarcoma. There are twice as many participants in the brigimadlin + ezabenlimab group and in the chemotherapy group, compared to those in the ezabenlimab group. Participants can continue treatment in the study as long as they benefit from it and can tolerate it. Doctors regularly check the size of the tumor and check whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects. Participants in this study use an app on a mobile phone to regularly answer questions about their health and well-being. This is to find out if their quality of life is changing.

Conditions

Advanced Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma (UPS); Myxofibrosarcoma (MFS)

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  Progression-free survival is defined as the time from randomization until the earliest of tumor progression according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, based on blinded central independent review or death from any cause.

  up to 4 years.

• Overall survival

  Overall survival, defined as the time from randomization until death from any cause.

  up to 4 years.

Secondary Outcomes (12)

• Objective response

  up to 4 years.

• Duration of objective response

  up to 4 years.

• Disease control

  up to 4 years.

• Duration of disease control

  up to 4 years.

• Occurrence of treatment-emergent adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5

  up to 4 years.

Study Arms (3)

Arm A: Ezabenlimab

EXPERIMENTAL

Drug: Ezabenlimab

Arm B: Brigimadlin + ezabenlimab

EXPERIMENTAL

Drug: Brigimadlin; Drug: Ezabenlimab

Arm C: Gemcitabine + docetaxel

ACTIVE COMPARATOR

Drug: Gemcitabine; Drug: Docetaxel

Interventions

Brigimadlin DRUG

Brigimadlin

Also known as: BI 907828

Arm B: Brigimadlin + ezabenlimab

Ezabenlimab DRUG

Ezabenlimab

Also known as: BI 754091

Arm A: Ezabenlimab; Arm B: Brigimadlin + ezabenlimab

Gemcitabine DRUG

Solution for infusion

Arm C: Gemcitabine + docetaxel

Docetaxel DRUG

Solution for infusion

Arm C: Gemcitabine + docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 - Good clinical practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
• Male or female patients ≥18 years old at the time of signature of the ICF
• Histologically proven diagnosis of one of the following:
• Undifferentiated pleomorphic sarcoma (UPS) with TP53 wild-type status
• Myxofibrosarcoma (MFS) with TP53 wild-type status
• Written pathology report indicating the diagnosis of UPS or MFS must be available
• Written report from the trial central laboratory indicating TP53 wild-type status
• One prior systemic regimen for advanced disease with documented progressive disease as per serial radiologic imaging. If prior systemic cytotoxic treatment for soft tissue sarcoma was given in a neoadjuvant, adjuvant or perioperative setting that treatment would count as one line of therapy in case of radiological progression during that treatment or within 3 months after completing that systemic therapy. If progression or relapse occurred after \>3 months after completing that systemic therapy, the pre-, post or perioperative treatment would not count as a line of treatment for advanced disease
• Patient must be willing to donate mandatory blood and tissue samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses

You may not qualify if:

• Prior treatment with immunotherapy in the context of anticancer therapy
• Previous administration of gemcitabine, taxanes, brigimadlin or any other mouse double minute 2 homolog-p53 (MDM2-p53) or MDMX (MDM4)-p53 antagonist
• Previous or concomitant malignancies other than the one treated in this trial 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
• Patient unable to swallow the trial medication
• Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug (e.g., nausea, vomiting, Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption) in the opinion of the investigator
• Active bleeding, significant risk of hemorrhage (e.g., previous severe gastrointestinal bleeding, previous hemorrhagic stroke at any time), or current bleeding disorder (e.g., hemophilia, von Willebrand disease)
• Known history of severe hypersensitivity reactions to other monoclonal antibodies or known hypersensitivity or known contraindication to the trial medications or their excipients

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Related Links

• Related Info

MeSH Terms

Conditions

Histiocytoma, Malignant Fibrous; Dermatofibrosarcoma

Interventions

brigimadlin; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Fibrosarcoma

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 17, 2024
• Study Start: June 27, 2024
• Primary Completion (Estimated): July 3, 2026
• Study Completion (Estimated): October 13, 2028
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.