A Study to Test Different Doses of BI 1831169 Alone and in Combination With Ezabenlimab in People With Different Types of Advanced Cancer (Solid Tumors)

Study Overview
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Brief Summary
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This study is open to adults with different types of advanced cancer (solid tumours) that are accessible for injection. People for whom previous treatment was not successful or for whom no other treatment options exist can join the study. The study tests a medicine called BI 1831169 alone and in combination with another medicine called ezabenlimab. BI 1831169 and ezabenlimab may help the immune system fight cancer. In this study, BI 1831169 is given to people for the first time. The study has 2 parts. The purpose of the first part is to find the highest dose of BI 1831169 the participants can tolerate. Part 1 also tests whether BI 1831169 can make the tumours shrink. The purpose of the second part is to find the highest dose of BI 1831169 in combination with ezabenlimab that the participants can tolerate. Participants get BI 1831169 as an injection into the tumour, or as an infusion into the vein, or both (injection and infusion). Ezabenlimab is given as an infusion into a vein. Participants get the medicines about every 3 weeks. Participants who get BI 1831169 alone receive this treatment for up to 3 months. Participants who take the combination treatment, get BI 1831169 for up to 3 months and ezabenlimab for up to a year. Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by BI 1831169 or ezabenlimab.

Official Title
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Phase I Open-label, Dose Escalation Trial of BI 1831169 Monotherapy and in Combination With Ezabenlimab in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: BI 1831169
* Drug: ezabenlimab


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 or relapsed/refractory solid tumor. Has accessible lesion(s), the number of accessible lesions depending on the arm into which the patient will be enrolled; either: For patients being enrolled into an intratumoral (i.t.) containing arm (Arms A, C, D, F), at least one accessible lesion is required, although two are preferred. The lesion(s) must either be easily accessible, or, if not easily accessible, patient must be willing to undergo repeat procedures (e.g., imaging guided procedures) for both biopsies and injections of BI 1831169. If only one accessible lesion is available, this lesion must have a minimum lesion diameter of ≥10mm for injection of BI 1831169 and be amenable to biopsy. If two accessible lesions are available, one must have a minimum lesion diameter of ≥10mm for injection of BI 1831169 and be amenable to biopsy, and the other must be amenable to biopsy. or For patients being enrolled into an intravenous (i.v.) only arm (Arms B and E), at least one accessible lesion which is amenable to biopsy. The lesion must either be easily accessible, or, if not easily accessible, patient must be willing to undergo repeat procedures (e.g., imaging guided procedures) for biopsies. Has failed conventional treatment or for whom no therapy of proven efficacy exists, who is not eligible for established treatment options or for whom the available treatment options are not suitable. Patient must have exhausted available treatment options known to prolong survival for their disease or have refused established treatment options for the malignant disease. Medically fit and willing to undergo all mandatory trial procedures. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Adequate organ function or bone marrow reserve as demonstrated at screening by the following laboratory values: Absolute neutrophil count ≥ 1.5x10^9/L (≥ 1.5x10^3/μL, ≥ 1500/mm^3); platelet count ≥ 100x10^9/L (≥ 100x10^3/μL, ≥ 100x10^3/mm3), without the use of hematopoietic growth factors within 4 weeks of start of trial medication Hemoglobin ≥ 90 g/L (≥ 9.0 g/dL, ≥ 5.6 mmol/L); Creatinine ≤ 1.5 times the upper limit of normal (ULN) Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases. Total bilirubin ≤ 1.5 x ULN, except for patients with Gilbert's syndrome: total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN partial thromboplastin time (PTT) / Activated partial thromboplastin time (aPTT) <1.5 x ULN All toxicities related to previous anti-cancer therapies (including Immune-related Adverse Event (irAEs)) have resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) grade 1 prior to the start of trial treatment (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). Any toxicity exceptions not listed here that should not impact the patient's participation per the Investigator's judgement should be discussed and agreed with the Sponsor. Patients ≥ 18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the Informed Consent Form (ICF). Further inclusion criteria apply. Exclusion Criteria: Major surgery (major according to the Investigator's assessment) performed within 4 weeks prior to start of study treatment. Radiotherapy within 4 weeks prior to the start of study treatment, except in case of a brief course of palliative radiotherapy (e.g., for analgesic purpose or for lytic lesions at risk of fracture) which can then be completed within two weeks prior to start of study treatment. Note: No radiation must have been given to any lesions planned to be injected and/or biopsied within 6 months of start of treatment. Active hepatitis B or C infection e.g., Hepatitis B surface antigen (HBsAg) positive, or hepatitis C (HCV) antibody (anti-HCV) positive (except if HCV-Ribonucleic Acid (RNA) negative), which in the opinion of the Investigator may interfere with participation in the trial. Patients with history of human immunodeficiency virus (HIV) infection who meet one or more of the following criteria; CD4+ count < 350 cells/μL Viral load > 400 copies/μL (local lab assessment) Not receiving antiretroviral therapy Receiving established antiretroviral therapy for less than four weeks prior to the start of study treatment History of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months prior to start of study treatment Patients with a history of HIV who do not meet any of the criteria above are eligible to participate but the patient must be under the care of an HIV/Infectious Diseases specialist or an HIV/Infectious Diseases specialist must be consulted prior to inclusion. Any severe or serious, acute or chronic medical or psychiatric condition or laboratory abnormality as per Investigator's judgement that may increase the risk associated with study participation or study drug administration, including ongoing or active infection requiring systemic antibiotics. Presence of brain tumors, brain metastases and / or carcinomatous meningitis (as per cranial imaging Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT), performed at most 6 weeks prior to first treatment). Active infection requiring systemic therapy (antibacterial, antiviral, antiparasitic or antifungal therapy) at the start of treatment in the trial. History of allergy or hypersensitivity to study agent components. Further or 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Monotherapy): Arm A<br>Arm A: Intratumoral (i.t.) administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>|
| Experimental: Part 1 (Monotherapy): Arm B<br>Arm B: Intravenous (i.v.) administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>|
| Experimental: Part 1 (Monotherapy): Arm C<br>Arm C: i.t.+i.v. administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>|
| Experimental: Part 2 (Combination therapy): Arm D<br>Arm D: Intratumoral (i.t.) administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>Drug: ezabenlimab<br>* ezabenlimab; Intravenous (i.v.)<br>|
| Experimental: Part 2 (Combination therapy): Arm E<br>Arm E: Intravenous (i.v.) administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>Drug: ezabenlimab<br>* ezabenlimab; Intravenous (i.v.)<br>|
| Experimental: Part 2 (Combination therapy): Arm F<br>Arm F: i.t.+i.v. administration | Drug: BI 1831169<br>* BI 1831169; Intratumoral (i.t.) and/or Intravenous (i.v.)<br>Drug: ezabenlimab<br>* ezabenlimab; Intravenous (i.v.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 (Monotherapy), Dose escalation: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period. | Used to determine the MTD and/or recommended monotherapy phase II dose (mRP2D) of BI 1831169 for Intratumoral (i.t.) only administration, Intravenous (i.v.) only administration, and combined i.t. and i.v. administration. | up to 21 days | 
| Part 1 (Monotherapy), Dose expansion: Objective response (OR) defined as best overall response (BOR) of confirmed intratumoral immunotherapy complete response (itCR) or confirmed partial response (itPR) | BOR is defined according to Response Criteria for Intratumoral Immunotherapy in Solid Tumors (itRECIST). BOR will consider all tumor assessments from first administration of trial medication until disease progression or death (whichever occurs first) or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. | up to 49 months | 
| Part 2 (Combination Therapy), Dose escalation: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period. | Used to determine the MTD and/or recommended combination therapy phase II dose (cRP2D) of BI 1831169 and ezabenlimab, for three different routes of administration of BI 1831169: Intratumoral (i.t.) only, Intravenous (i.v.) only, and combined i.t. and i.v. | up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 (Monotherapy), Dose escalation: Number of patients experiencing DLTs during all treatment cycles. |  | up to 49 months | 
| Part 1 (Monotherapy), Dose escalation: Number of patients with adverse events during the on-treatment period. |  | up to 49 months | 
| Part 1 (Monotherapy), Dose expansion: Number of patients with adverse events during the on-treatment period. |  | up to 49 months | 
| Part 2 (Combination Therapy), Dose escalation: Number of patients experiencing DLTs during all treatment cycles. |  | up to 49 months | 
| Part 2 (Combination Therapy), Dose escalation: Number of patients with adverse events during the on-treatment period. |  | up to 49 months |