DAREON™-9: A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With Small Cell Lung Cancer When Taken Together With Topotecan

Study Overview
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Brief Summary
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This study is open to adults with extensive stage small cell lung cancer. The study is in people with advanced cancer that had previously received platinum-based chemotherapy and are eligible to receive topotecan treatment. The purpose of this study is to find out the highest dose of BI 764532 that people can tolerate when taken together with topotecan. BI 764532 is an antibody-like molecule that may help the immune system fight cancer. Participants get BI 764532 and topotecan as infusions into a vein. As an alternative, topotecan may also be taken orally (tablets). Participants may continue to take BI 764532 as long as they benefit from treatment and can tolerate it. During this time, participants visit the study site regularly. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.

Official Title
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DAREON™-9: A Phase Ib Open-label Dose Escalation and Dose Confirmation Safety Study of Intravenous BI 764532 in Combination With Topotecan for the Treatment of Patients With Small Cell Lung Cancer

Conditions
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Small Cell Lung Carcinoma (SCLC)

Intervention / Treatment
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* Drug: BI 764532
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥18 years old and at least at the legal age of consent in countries where it is greater than 18 years at the time of signature of the informed consent form (ICF). Signed and dated written informed consent in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Histologically or cytologically confirmed small cell lung cancer (SCLC) Extensive stage - small cell lung cancer (ES-SCLC) that progressed or recurred following platinum-based treatment, and anti- programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) as applicable Patients must be eligible for topotecan treatment according to label Availability of archival tumour tissue sample Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Further inclusion criteria apply Exclusion Criteria: Previous treatment in this trial Current enrolment in another investigational device or drug trial, or <30 days since ending another investigational device or drug trial(s) Untreated or symptomatic brain metastases. Participants with treated, stable brain metastases are eligible provided they meet the following criteria: Radiotherapy or major surgery for brain metastases was completed at least 2 weeks (for radiotherapy) or 4 weeks (for major brain metastases surgery) prior to the first administration of BI 764532. Patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant central nervous system (CNS) disease. Presence of leptomeningeal carcinomatosis Previous treatment with T cell engager (TcE) or cell therapies targeting delta-like ligand 3 (DLL3). Persistent toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, asthenia/fatigue, CTCAE Grade 2 neuropathy, or Grade 2 endocrinopathies controlled by replacement therapy). Major surgery (major according to the investigator's assessment) within 28 days prior to first administration of BI 764532 or planned during treatment period, e.g. hip replacement. 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 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: BI 764532 low dose + topotecan<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Topotecan<br>* Topotecan<br>|
| Experimental: Part A: BI 764532 medium dose + topotecan<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Topotecan<br>* Topotecan<br>|
| Experimental: Part A: BI 764532 high dose + topotecan<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Topotecan<br>* Topotecan<br>|
| Experimental: Part B: BI 764532 + topotecan<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Topotecan<br>* Topotecan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period |  | up to 9 weeks | 
| Part B: Occurrence of DLTs during the on-treatment period |  | up to 36 months | 
| Part B: Occurrence of AEs during the on-treatment period |  | up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Occurrence of DLTs during the on-treatment period |  | up to 36 months | 
| Part A: Occurrence of AEs during the on-treatment period |  | up to 36 months | 
| Part B: Objective response |  | up to 36 months | 
| Part B: Duration of response |  | up to 36 months |