A Study to Test Different Doses of BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors)

Study Overview
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Brief Summary
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This study is open to adults with advanced cancer (solid tumors). People for whom previous treatment was not successful can take part in this study. The purpose of this study is to find the highest dose of a medicine called BI 765179 that people with solid tumors can tolerate when taken alone or together with a medicine called ezabenlimab. Each participant is put into one of two groups. Participants get BI 765179 alone or in combination with ezabenlimab as infusion into a vein every 3 weeks. BI 765179 and ezabenlimab are antibodies that may help the immune system fight cancer. In this study, BI 765179 is given to people for the first time. Participants can stay in the study up to 3 years if they benefit from treatment and can tolerate it. The doctors regularly check the participants' health and note any health problems that could have been caused by the study treatment.

Official Title
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An Open Label, Phase I Dose-finding Study of BI 765179 as Monotherapy and in Combination With Ezabenlimab (BI 754091) in Patients With Advanced Solid Cancers

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BI 765179
* Drug: Ezabenlimab


Participation Criteria
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Eligibility Criteria
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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) 1.1 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)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. 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 informed consent (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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: BI 765179<br> | Drug: BI 765179<br>* BI 765179<br>|
| Experimental: Arm B: BI 765179 + ezabenlimab<br> | Drug: BI 765179<br>* BI 765179<br>Drug: Ezabenlimab<br>* Ezabenlimab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | MTD is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period. The MTD will be assessed based on the number of patients experiencing DLTs, graded according to Common terminology criteria for adverse events (CTCAE) version 5.0, during the MTD evaluation period. | Up to Day 21 (end of Cycle 1) | 
| Number of patients experiencing Dose Limiting Toxicities (DLTs) in the MTD evaluation period |  | Up to Day 21 (end of Cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing DLTs during the on-treatment period (per arm) |  | up to 36 months | 
| Maximum measured concentration of BI 765179 in plasma (Cmax) |  | Up to Day 21 (end of Cycle 1) | 
| Area under the concentration-time curve of BI 765179 in plasma over a uniform dosing interval from zero to 504h (AUC0-504) |  | Up to Day 21 (end of Cycle 1) | 
| Maximum measured concentration of BI 765179 in plasma at steady state (Cmax,ss) |  | up to Day 84 (end of Cycle 4) | 
| Area under the concentration-time curve of BI 765179 in plasma at steady state over a uniform dosing interval 504h (AUC0-504,ss) |  | Up to Day 84 (end of Cycle 4) |