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

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 - Good clinical practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
2. Male or female patients ≥18 years old at the time of signature of the ICF
3. Histologically proven diagnosis of one of the following:

   * Undifferentiated pleomorphic sarcoma (UPS) with TP53 wild-type status
   * Myxofibrosarcoma (MFS) with TP53 wild-type status
4. Written pathology report indicating the diagnosis of UPS or MFS must be available
5. Written report from the trial central laboratory indicating TP53 wild-type status
6. 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
7. Patient must be willing to donate mandatory blood and tissue samples for the pharmacokinetics, pharmacodynamics, and biomarker analyses
8. Presence of at least one target lesion according to RECIST Version 1.1 Further inclusion criteria apply

Exclusion Criteria:

1. Prior treatment with immunotherapy in the context of anticancer therapy
2. Previous administration of gemcitabine, taxanes, brigimadlin or any other mouse double minute 2 homolog-p53 (MDM2-p53) or MDMX (MDM4)-p53 antagonist
3. 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
4. Patient unable to swallow the trial medication
5. 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
6. 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)
7. Known history of severe hypersensitivity reactions to other monoclonal antibodies or known hypersensitivity or known contraindication to the trial medications or their excipients
8. Active autoimmune disease or a documented history of autoimmune disease, that requires systemic treatment, i.e., corticosteroids or immunosuppressive drugs, except for vitiligo or resolved childhood asthma/atopy, alopecia, or any chronic skin condition that does not require systemic therapy; patients with autoimmune-related hypothyroidism on a stable dose of thyroid hormone replacement and/or controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible Further exclusion criteria apply