DAREONᵀᴹ-8: A Study to Test How Well Different Doses of BI 764532 in Addition to Standard of Care Are Tolerated by People With Advanced Small Cell Lung Cancer

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 are eligible for standard of care including chemotherapy and anti-PD-L1 (Programmed Cell Death Ligand 1) immunotherapy. The purpose of this study is to find out the highest dose of BI 764532 that people can tolerate when taken together with standard of care. BI 764532 is an antibody-like molecule that may help the immune system fight cancer. Participants get BI 764532 and different standard treatments as infusions into a vein. If there is benefit for the participants and if they can tolerate it, the treatment is given for the entire duration of the study. 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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DAREONᵀᴹ-8: A Phase I, Open-label, Dose Escalation and Expansion Trial of Repeated Intravenous Infusions of BI 764532 Combined With Standard of Care (Platinium, Etoposide, and Anti-PD-L1) in Patients With Extensive-stage Small Cell Lung Carcinoma

Conditions
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Small Cell Lung Carcinoma (SCLC)

Intervention / Treatment
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* Drug: BI 764532
* Drug: Carboplatin
* Drug: Etoposide
* Drug: Atezolizumab
* Drug: Durvalumab
* Drug: Cisplatin


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 Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Histologically or cytologically confirmed extensive-stage small cell lung carcinoma (ES-SCLC) Availability of archival tumour tissue Patients must be eligible for platinum+etoposide+anti-Programmed Cell Death Ligand 1 (PD-L1) regimen as first line standard of care (SoC) treatment: In Part A, patients must be eligible to receive carboplatin + etoposide + atezolizumab In Part B, patients must be eligible to receive etoposide, carboplatin or cisplatin, and atezolizumab or durvalumab No prior systemic treatment for ES-SCLC Prior systematic anti-cancer treatment for limited-stage small cell lung cancer (SCLC) must have been complete at least 6 months prior to the diagnosis of ES-SCLC Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Further inclusion criteria apply. Exclusion Criteria: Previous treatment in this trial Treatment with a systemic anti-cancer therapy or investigational drug within 28 days or 5 half-lives (whichever is shorter) of the first administration of trial medication Presence of leptomeningeal carcinomatosis Previous treatment with Delta-like ligand 3 (DLL3)-targeting T cell engagers and cell therapies Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 1 week prior to first administration of BI 764532 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 Any documented active or suspected malignancy or history of malignancy within 5 years prior to Screening (other than the target indication), except for appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix 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 - Dose escalation: BI 764532 very low dose + carboplatin + etoposide + atezolizumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Atezolizumab<br>* Atezolizumab<br>|
| Experimental: Part A - Dose escalation: BI 764532 low dose + carboplatin + etoposide + atezolizumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Atezolizumab<br>* Atezolizumab<br>|
| Experimental: Part A - Dose escalation: BI 764532 medium dose + carboplatin + etoposide + atezolizumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Atezolizumab<br>* Atezolizumab<br>|
| Experimental: Part A - Dose escalation: BI 764532 high dose + carboplatin + etoposide + atezolizumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Atezolizumab<br>* Atezolizumab<br>|
| Experimental: Part B - Dose expansion: BI 764532 + carboplatin + etoposide + atezolizumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Atezolizumab<br>* Atezolizumab<br>|
| Experimental: Part B - Dose expansion: BI 764532 + carboplatin + etoposide + durvalumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Etoposide<br>* Etoposide<br>Drug: Durvalumab<br>* Durvalumab<br>|
| Experimental: Part B - Dose expansion: BI 764532 + cisplatin + etoposide + durvalumab<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Etoposide<br>* Etoposide<br>Drug: Durvalumab<br>* Durvalumab<br>Drug: Cisplatin<br>* Cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - Dose escalation: Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period |  | up to 6 weeks | 
| Part B - Dose expansion: Occurrence of dose limiting toxicities (DLTs) during the on-treatment period |  | up to 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A - Dose escalation: Occurrence of dose limiting toxicities (DLTs) during the on-treatment period |  | up to 23 months | 
| Part A - Dose escalation: Occurrence of adverse events (AEs) during the on-treatment period |  | up to 23 months | 
| Part B - Dose expansion: Objective response (OR) | OR is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 (based on investigator's assessment) from the date of treatment start until the earliest date of disease progression, death, or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent | up to 23 months | 
| Part B - Dose expansion: Duration of response (DoR) | DoR is defined as the time from first documented confirmed objective response (OR) until the earliest date of disease progression or death among patients with confirmed objective response | up to 23 months |