Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder

Inclusion Criteria:

• Diagnosis of a solid tumour which meets the criteria for an open trial cohort:

• Cohorts 1 and 1-CN (biliary tract adenocarcinoma): Locally advanced ormetastatic biliary tract adenocarcinoma (intra- and extrahepaticcholangiocarcinoma, gallbladder cancer, and ampullary cancer).Patients musthave unresectable disease and have received all available conventionaltherapies known to confer clinical benefit for their disease based on localapproved standards; or (in the opinion of the investigator) patients areunlikely to tolerate or derive clinically meaningful benefit from appropriatestandard of care therapy.

• Cohort 2 (pancreatic ductal adenocarcinoma): Locally advanced or metastaticpancreatic ductal adenocarcinoma. Patients must have unresectable disease andhave received all available conventional therapies known to confer clinicalbenefit for their disease based on local approved standards.

• Cohort 3 (lung adenocarcinoma): Locally advanced or metastatic lungadenocarcinoma. Patients must have unresectable disease and have received allavailable conventional therapies known to confer clinical benefit for theirdisease based on local approved standards.

• Cohort 4 (urothelial bladder cancer): Locally advanced or metastatic urothelialbladder cancer. Patients must have unresectable disease and have received allavailable conventional therapies known to confer clinical benefit for theirdisease based on local approved standards.

• Written pathology report / molecular profiling report indicating Mouse double minute 2 homolog (MDM2) amplification or a copy number ≥8 and tumor protein 53 (TP53)wild-type status. This must have been confirmed with a tissue-based test. A testwith liquid biopsy is not accepted.

• Archival tissue (formalin fixed paraffin embedded [FFPE] tumour blocks or slides)must be provided for retrospective confirmation of MDM2 amplification and TP53status.

• Presence of at least 1 measurable target lesion according to Response EvaluationCriteria in Solid Tumours (RECIST) version 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

• Patient must be willing to donate mandatory blood samples for the pharmacokinetics,pharmacodynamics, and biomarker analyses

• Adequate organ function

• All toxicities related to previous anti-cancer therapies have resolved to ≤CommonTerminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatmentadministration (except for alopecia and amenorrhea / menstrual disorders which canbe of any grade and peripheral neuropathy which must be ≤CTCAE Grade 2).

• Life expectancy ≥3 months at the start of treatment in the opinion of theinvestigator.

• Provision of signed and dated, written informed consent form (ICF) in accordancewith 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. Women ofchildbearing potential (WOCBP) and men able to father a child must be ready and ableto use 2 medically acceptable methods of birth control per ICH M3 (R2) that resultin a low failure rate of less than 1% per year when used consistently and correctlybeginning at screening, during trial participation, and until 6 months and 12 daysafter last dose for women and 102 days after last dose for men. A list ofcontraception methods meeting these criteria is provided in the patient information.

Exclusion Criteria:

• Previous administration of brigimadlin (BI 907828) or any other MDM2-p53 or mousedouble minute 4 (MDMX, MDM4)-p53 antagonist.

• Active bleeding, significant risk of haemorrhage (e.g. previous severegastrointestinal bleeding, previous haemorrhagic stroke at any time), or currentbleeding disorder (e.g. haemophilia, von Willebrand disease).

• Major surgery (major according to the investigator's assessment) performed within 4weeks prior to start of trial treatment or planned within 6 months after screening (e.g. hip replacement).

• Clinically significant previous or concomitant malignancies in the opinion of theinvestigator affecting the efficacy and/or outcome of the trial.

• Patients who must or intend to continue the intake of restricted medications or anydrug considered likely to interfere with the safe conduct of the trial.

• Currently enrolled in another investigational device or drug trial.

• Any history of, or concomitant condition that, in the opinion of the investigator,would compromise the patient's ability to comply with the trial or interfere withthe evaluation of the safety and efficacy of the trial drug.

• Patients not expected to comply with the protocol requirements or not expected tocomplete the trial as scheduled (e.g. chronic alcohol or drug abuse or any othercondition that, in the investigator's opinion, makes the patient an unreliable trialparticipant).

Further exclusion criteria apply.