A Study to Test Different Doses of BI 836880 Combined With Ezabenlimab in Patients With Advanced Non-small Cell Lung Cancer Followed by Other Types of Advanced Solid Tumours

Inclusion Criteria

Part 1:

• Of full age (according to local legislation, usually ≥ 18 years) at screening.
• Pathologically confirmed locally advanced or metastatic non-squamous NSCLC with PDL-1 expression available and >1% by IHC (as defined by the Pembrolizumab companion diagnostic test, determined by appropriate local pathology lab.
• No previous treatment with check-point inhibitor. Or patients with checkpoint inhibitor based treatment as last therapy before entering the trial.
• Documented disease progression or relapse (based on investigator's assessment) during or after completion of at least 2 cycles of platinum-based chemotherapy as first line treatment of Stage IIIB/IV non- squamous NSCLC or for checkpoint inhibitor experienced patients during or after completion of at least 2 cycles of platinum-based chemotherapy and a checkpoint inhibitor treatment (monotherapy or in combination with chemotherapy). This includes patients relapsing within 6 months of completing (neo)adjuvant/curative-intent chemotherapy/CPI or chemoradiotherapy
• At least one target lesion (outside the brain) that can be accurately measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 .
• Lesion with a diameter ≥ 2cm assessed by radiologist as suitable for DCE-MRI evaluation (Mandatory in Part 1, optional in Part 2)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy ≥ 3 months after start of the treatment in the opinion of the investigator
• Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia (any grade), sensory peripheral neuropathy , must be ≤ CTCAE grade 2 or considered not clinically significant.
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
• Availability and willingness to provide a fresh tumour tissue sample obtained at baseline, and after 2 cycles of treatment
• Adequate organ function defined as all of the following (all screening labs should be performed at local lab within 10 days prior to treatment initiation)
• Male or female patients. Women of childbearing potential (WOCBP)1 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, starting with the screening visit and through 6 months after the last dose of BI 836880 and BI 754091 treatment, respectively. A list of contraception methods meeting these criteria is provided in the patient information Note: Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study medication during the screening period. At the following visits according to the flowchart a urine and/or serum pregnancy test is required. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.

Part 2:

• Of full age (according to local legislation, usually ≥ 18 years) at screening
• At least one measurable target lesion outside the brain (excluding the glioblastoma patients where brain lesions are allowed), that can be accurately measured per RECIST version 1.1 or Response Assessment in Neuro-Oncology (RANO)
• ECOG performance status ≤ 1 (For glioblastoma cohort Karnofsky status is applicable)
• Adequate organ function as all of the following (all screening labs should be performed at local lab within approximately 72 hours prior to treatment initiation)
• Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. For Part 2, In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1)