Studio per testare BI 765179 da solo e in combinazione con ezabenlimab in pazienti con cancro avanzato (tumori solidi) e BI 765179 in combinazione con pembrolizumab in pazienti con cancro avanzato della testa e del collo

Inclusion Criteria:

All cohorts:

* Patients with locally advanced, unresectable or metastatic solid tumors who are either refractory after standard therapy for the disease or for whom standard therapy is not appropriate
* Tumor with expected high expression of Fibroblast activation protein (FAP) of the following histologies:

  * Non-small cell lung carcinoma (NSCLC)
  * Gastric cancer
  * Esophageal adenocarcinoma or squamous cell carcinoma
  * Urothelial bladder carcinoma
  * Head and neck squamous cell carcinoma
  * Cutaneous malignant melanoma
  * Cutaneous squamous cell carcinoma
  * Hepatocellular carcinoma
  * Pancreatic adenocarcinoma
  * Colorectal cancer
  * Malignant pleural mesothelioma
  * Cervical squamous cell cancer
  * Ovarian carcinoma
  * Triple-negative breast cancer
* At least 18 years of age at the time of the consent or over the legal age of consent in countries where that is greater than 18 years
* Signed and dated, written informed consent (IC) in accordance with ICH-GCP and local legislation prior to admission to the trial
* At least one measurable lesion outside of central nervous system (CNS) as defined per modified Response evaluation criteria in solid tumors (RECIST) v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate liver, bone marrow and renal organ function
* Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. These methods must be used during the study and for at least 6 months after the last dose of the study medication. A list of contraception methods meeting these criteria is provided in the patient information.
* Patients with brain metastases are eligible provided they meet all of the following criteria:

  * Brain metastases have adequately been treated and are considered stable by the Investigator
  * Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of BI 765179
  * Patient is off steroids for at least 7 days (physiologic doses of steroids is permitted, if this was stable for the last 4 weeks)
  * The patient is off anti-epileptic drugs for at least 7 days

Back-fill cohorts only:

* Patient has agreed to and signed an IC form to provide mandatory pre-treatment and on-treatment fresh tumor biopsy
* At least one lesion (separate from the evaluable target lesion outside of the CNS as defined per RECIST v1.1) that is accessible for mandatory paired pre and on-treatment biopsy

Phase 1b:

* Histologically or cytologically confirmed diagnosis of metastatic or incurable, recurrent head and neck squamous cell carcinoma (HNSCC)
* No prior systemic therapy administered in the metastatic or incurable, recurrent setting
* Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx
* At least 18 years of age at the time of the consent or over the legal age of consent in countries where that is greater than 18 years
* Signed and dated written IC in accordance with ICH-GCP and local legislation prior to admission to the trial Further inclusion criteria apply

Exclusion Criteria:

Phase 1a

* Currently enrolled in another investigational device or drug trial
* Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:

  * Effectively treated non-melanoma skin cancers
  * Effectively treated carcinoma in situ of the cervix
  * Effectively treated ductal carcinoma in situ
  * Other effectively treated malignancy that is considered cured by 'local treatment'
* Previous treatment with agents targeting CD137
* Known leptomeningeal disease or spinal cord compression due to disease
* Anticoagulant treatment that cannot be safely interrupted if medically needed (e.g., biopsy) based on the opinion of the Investigator
* Persistent toxicity from previous treatments that has not resolved to ≤ Common terminology criteria for adverse events (CTCAE) Grade 1 (except for alopecia, CTCAE Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by replacement therapy)
* Patient has a diagnosis of immunodeficiency
* Patient with history of immunosuppressive medication within 14 days prior to the first dose of BI 765179. The following are exceptions to this criterion:

  * Use of intranasal, inhaled, or topical corticosteroids, local steroid injections (e.g., intra-articular injections)
  * Systemic corticosteroids at physiologic doses ≤10 mg/day (prednisone or equivalent)
  * Physiological replacement dose of corticosteroids Further exclusion criteria apply.

Phase Ib

* Disease suitable for local therapy administered with curative intent
* Participants must not have a primary tumor site of nasopharynx or sino-nasal cancer or salivary gland cancers (any histology)
* Currently enrolled in another investigational device or drug trial
* Life expectancy of <3 months and/or has rapidly progressing disease
* Diagnosed and/or treated additional malignancy within 2 years prior to randomization with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or in situ breast cancers Further exclusion criteria apply