Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Histiocytoma, Malignant Fibrous

Histiocytoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Gemcitabine

Docetaxel

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Brigimadlin

Ezabenlimab

Boehringer Ingelheim

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.

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

Brightline-3: A Phase III, Randomized, Open-label, Multi-center Trial of Brigimadlin + Ezabenlimab Compared to Gemcitabine + Docetaxel for Second-line Treatment of Patients With Advanced TP53 Wild-type Soft Tissue Sarcoma Subtypes

Once the criteria in section "Time Frame" are fulfilled, 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 in the website.

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.

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

Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST Version 1.1 (based on central independent review) from the date of randomization until the earliest of disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.

Duration of objective response (DOR), defined as the time from first documented confirmed OR according to RECIST Version 1.1 until the earliest of disease progression or death among patients with confirmed objective response (based on central independent review).

Disease control (DC), 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 central independent review).

Duration of disease control, defined as the time from randomization until the earliest of disease progression according to RECIST Version 1.1 (based on central independent review) or death from any cause among patients with disease control.

Fatigue will be assessed via 8 items. The score of each item ranges from 0-100 with higher scores indicating higher symptomology.

Fatigability will be assessed via 12 items. The score of each item ranges from 0-100 with higher scores indicating higher symptomology.

EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes (PROs). The gloabl health status and the quality of life are 2 of the 30 items and are scored from 1 (1=very poor) to 7 (7=excellent).

All other items have 4 possible scores (1= not at all, 2= a little, 3=quite a bit, 4=very much).

Spots Global Cancer Trial Database for undifferentiated pleomorphic sarcoma (ups)