Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours

Study Overview
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Brief Summary
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This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Such therapies are also called immune checkpoint inhibitors. How long the participants are in the study depends on whether they benefit from treatment and whether they experience unacceptable side effects. The participants are put into different groups. Each group receives BI 754091 in combination with another medicine. The doctors check whether the tumors shrink or disappear. The doctors also check the general health of the participants.

Official Title
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An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 (Ezabenlimab) Anti-PD-1 Based Combination Regimens in PD-(L)1 naïve and PD-(L)1 Pretreated Patient Populations With Advanced and/or Metastatic Solid Tumours Who Have Had at Least One Line of Systemic Therapy

Conditions
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Neoplasm Metastasis

Intervention / Treatment
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* Drug: BI 754091
* Drug: BI 754111
* Drug: BI 836880


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Master Protocol: Provision of signed and dated, written Master informed consent form (ICF) prior to any trial-specific procedures, sampling, or analyses. Patient ≥18 years of age at the time of signature of the ICF. Eastern Cooperative Oncology Group (ECOG) score: 0 or 1. Patient must agree to a pre-treatment biopsy (if archival tissue is not available) and on-treatment tumour biopsy. Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be willing and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly) during trial participation and for at least 6 months after the last administration of trial medication. Module A: - Histologically confirmed diagnosis of one of the following cohorts: Cohort 1 GEC - Locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro oesophageal adenocarcinoma (GEC) (defined as primary tumour localisation below the gastro oesophageal junction (GEJ) with prior anti-PD-1 or anti-PD-L1 based treated tumour. Cohort 2 Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour with previously anti-PD-1 or anti-PD-L1 based treatment who progressed after achieving benefit Cohort 3 Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD- 1/PD-L1 based treated tumour without achieving benefit. All patients must have measurable lesions according to RECIST v1.1 Patient must agree to pre- and on-treatment tumour biopsies. If archived tumour tissue is available from the last treatment failure, sections may be supplied instead of a pre-treatment biopsy. Module C: Histologically confirmed diagnosis of one of the following cohorts: Cohort 1: GEC: Locally advanced, unresectable or metastatic gastric adenocarcinoma or GEC. Cohort 2: Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour (excluding NSCLC and melanoma) with previously anti-PD-1 or anti-PD-L1 based treatment which progressed after achieving benefit. Cohort 3: Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD-1/PD-L1 based treated tumour without achieving benefit. Cohort 4: Locally advanced, unresectable or metastatic second line or greater, microsatellite stable (MSS) colorectal cancer. Cohort 5: Advanced Endometrial cancer: Endometrial carcinoma that is pMMR (Mismatch Repair-Proficient)/MSS and is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy. All patients must have at least one measurable lesion according to RECIST v1.1 Further inclusion criteria apply Exclusion Criteria Master Protocol: Any investigational treatment anti-tumour treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment. More than one anti-PD-(L)1-based treatment regimen prior to entering study Major surgery ('major' according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 months after screening, e.g., hip replacement. Known history of severe hypersensitivity reactions to other mAbs or known hypersensitivity to the trial drugs or their excipients. Presence of central nervous system (CNS) metastases, unless treated and asymptomatic and off corticosteroids and/or anticonvulsant therapy for at least 2 weeks prior to start of treatment. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study treatment. Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. Patients who were permanently discontinued from previous anti-PD-1 or anti-PD-L1 therapy because of a immune-related adverse event (irAE). Module A: - Previous treatment with an anti-LAG-3 Agent Module C: Unresolved, Grade >1 toxicity before the start of treatment with the study drug except for hair loss (alopecia) and hypothyroidism that requires thyroid hormone supplements but is asymptomatic under therapy. Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > New York Heart Association [NYHA] II) History of severe haemorrhagic or thromboembolic event in the past 12 months Known inherited predisposition to bleeding or to thrombosis, in the opinion of the investigator - 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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Module A<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 754111<br>* Solution for infusion<br>|
| Experimental: Cohort 2 - Module A<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 754111<br>* Solution for infusion<br>|
| Experimental: Cohort 3 - Module A<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 754111<br>* Solution for infusion<br>|
| Experimental: Cohort 1 - Module C<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 836880<br>* Solution for infusion<br>|
| Experimental: Cohort 2 - Module C<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 836880<br>* Solution for infusion<br>|
| Experimental: Cohort 3 - Module C<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 836880<br>* Solution for infusion<br>|
| Experimental: Cohort 4 - Module C<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 836880<br>* Solution for infusion<br>|
| Experimental: Cohort 5 - Module C<br> | Drug: BI 754091<br>* Solution for infusion<br>* Other names: ezabenlimab;Drug: BI 836880<br>* Solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the trial is objective response (OR), defined as best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the Investigator |  | Up to 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DoR), defined as the time from first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death among patients with OR |  | Up to 32 months | 
| Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) according to RECIST v1.1 as assessed by the Investigator |  | Up to 32 months | 
| Progression-free survival (PFS), defined as the time from first treatment until PD or death from any cause, whichever occurs earlier |  | Up to 32 months |