A Study to Find the Best Dose of BI 1387446 Alone or in Combination With Ezabenlimab (BI 754091) in Patients With Different Types of Advanced or Metastatic Cancer (Solid Tumors)

Study Overview
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Brief Summary
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This is a study in adults with advanced cancer (solid tumours) in whom previous treatment was not successful. The study tests 2 medicines called BI 1387446 and BI 754091. Both medicines may help the immune system fight cancer. In this study, BI 1387446 is given to humans for the first time. The purpose of this study is to find out the highest dose of BI 1387446 alone and in combination with BI 754091 the participants can tolerate. BI 1387446 is injected directly into the tumour. Participants get BI 1387446 injections every week at the beginning and then every 3 weeks. Some participants get BI 754091 in addition to BI 1387446. BI 754091 is given as an infusion into a vein every 3 weeks. As long as they benefit from treatment and can tolerate it, participants can stay in the study for up to 2 years and 8 months. During this time, they visit the study site regularly. At these visit, doctors record any unwanted effects. The doctors also regularly check participants' health.

Official Title
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Phase I, First in Human Trial Evaluating BI 1387446 Alone and in Combination With Ezabenlimab (BI 754091) in Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BI 1387446
* Drug: BI 754091


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic malignant solid tumor and indication for treatment Patient must have exhausted established treatment options known to prolong survival for the malignant disease, or is not eligible for established treatment options. Medically fit and willing to undergo all mandatory trial procedures. At least one tumor lesion which is suitable for injection (Screening/initial administration), appropriate for the allocated treatment arm, and measurable. At least 1 discrete lesion, in addition to the lesion proposed for injection, which is amenable to biopsy and is not located in the brain, mediastinum or pancreas. Adequate organ function or bone marrow reserve Further inclusion criteria apply Exclusion criteria: Any investigational or antitumour treatment (including antibodies targeting Programmed Cell Death-1 (PD1) - or programmed Death-Ligand 1 (PDL1)) within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initial administration of BI 1387446 or BI 754091. Persistent toxicity from previous treatments (including Immune-related Adverse Events (irAEs)) that has not resolved to ≤ Grade 1, except for alopecia, xerostomia, and immunotherapy related endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs as per Investigator judgement History or evidence of active, non-treatment related autoimmune disease, except for endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs. History or evidence of pneumonitis related to prior immunotherapy Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of BI 1387446 or BI 754091. The tumor at the projected injection site has a high risk for local complications, e.g. bleeding related to encasement/infiltration of major blood vessels or contact with liver capsule, compression of vital structures in case of swelling of injected lesion, in the opinion of the Investigator. Active infection requiring systemic therapy at the start of treatment in the trial, including active viral hepatitis infection or active tuberculosis infection. Cardiac insufficiency New York Heart Association (NYHA) III or IV Left ventricular ejection fraction < 50% measured by echocardiography or Multigated Acquisition (MUGA) scan Mean resting corrected QT interval (QTc) >470 msec Further exclusion criteria apply

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: BI 1387446<br>superficial lesions | Drug: BI 1387446<br>* intratumoral injection<br>|
| Experimental: Arm B: BI 1387446 in combination with ezabenlimab (BI 754091)<br>superficial lesions | Drug: BI 1387446<br>* intratumoral injection<br>Drug: BI 754091<br>* intravenous infusion<br>* Other names: ezabenlimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) based on number of Dose-limiting toxicities (DLTs) |  | 3 weeks | 
| Number of patients with Dose limiting Toxicity (DLT) in the Maximum tolerated dose (MTD) evaluation period |  | up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response |  | An average of 1 year | 
| Best percentage change from baseline in size of injected target lesions |  | An average of 1 year | 
| Best percentage change from baseline in size of non-injected target lesions |  | An average of 1 year |