DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers

Study Overview
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Brief Summary
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This study is open to adults with small cell lung cancer and other neuroendocrine tumours. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find a suitable dose of BI 764532 that people with advanced cancer can tolerate when taken alone. 2 different doses of BI 764532 are tested in this study. Another purpose is to check whether BI 764532 can make tumours shrink. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. Participants are put into 2 groups randomly, which means by chance. One group gets dose 1 of BI 764532 and the other group gets dose 2 of BI 764532. Participants get BI 764532 infusions into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include an over-night stay to monitor participants' safety. Doctors record any unwanted effects and regularly check the general health of the participants.

Official Title
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DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas

Conditions
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Small Cell Lung Carcinoma, Neuroendocrine Neoplasms

Intervention / Treatment
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* Drug: BI 764532


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, cancer of the following histologies: Small cell lung cancer (SCLC) Extra-pulmonary neuroendocrine carcinoma (epNEC) (except Merkel cell carcinoma (MCC), Medullary thyroid cancer (MTC) and Neuroendocrine prostate cancer (NEPC)) Large cell neuroendocrine carcinoma (LCNEC) of the lung Patients with tumours with mixed histologies for any above type are eligible only if the neuroendocrine carcinoma/small tumour cells component is predominant and represents at least 50% of the overall tumour tissue. Patients must have progressed or recurred after standard of care therapy SCLC: after at least two prior lines of therapy, including at least one platinum-based regimen epNEC/LCNEC: after at least one platinum-based regimen Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Measurable lesions as defined per Response Evaluation Criteria In Solid Tumours (RECIST) v 1.1 within 21 days prior to the first dose of BI 764532. Availability of archival tumour tissue sample. Adequate organ function as defined in the protocol. All toxicities related to previous anti-cancer therapies have resolved = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia and peripheral neuropathy which must be = CTCAE Grade 2 and amenorrhea/menstrual disorders which can be any grade). Women of childbearing potential (WOCBP)and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information Exclusion criteria: Untreated or symptomatic brain metastases. Participants with treated, stable brain metastases are eligible provided they meet the following criteria: Radiotherapy or surgery for brain metastases was completed at least 2 weeks 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 disease. Active/previous history of interstitial lung disease or non-infectious pneumonitis (any grade). Participants who experienced severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents. Prior anti-cancer therapy: Patients who have been treated with any other anti-cancer drug within 4 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 764532. Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of BI 764532. Previous treatment with Delta-like ligand 3 (DLL3)-targeting T cell engagers or cell therapies. Diagnosis of immunodeficiency or systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of BI 764532. Physiological replacement of steroids is allowed. Unresolved toxicity from prior anti-tumour therapy, defined as per protocol. 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose group 1<br> | Drug: BI 764532<br>* BI 764532<br>|
| Experimental: Dose group 2<br> | Drug: BI 764532<br>* BI 764532<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) | according to RECIST v 1.1 by investigator 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 | 
| Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period |  | up to 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of objective response (DOR) based on investigator assessment | DOR is defined as the time from first documented confirmed OR until the earliest date of disease progression or death among patients with confirmed OR. | up to 23 months | 
| Progression-free survival (PFS) based on investigator assessment | PFS is defined as the time from treatment start until the earliest date of tumour progression according RECIST v 1.1 or death from any cause, whichever occurs first. | up to 23 months | 
| Disease control (DC), defined as best overall response of CR or PR or stable disease (SD) based on investigator assessment | where best overall response is defined according to RECIST v 1.1, from first treatment administration until the earliest 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 | 
| Overall survival (OS), defined as the time from treatment start until death from any cause |  | up to 23 months | 
| Change from baseline in EORTC QLQ-C30 physical functioning domain score | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) The QLQ-C30 is comprised of 30 questions. It incorporates both multi-item scales and single-item measures. These include one global health status/Quality of Life (QoL) scale, five functional scales, three symptom scales and six single items to assess dyspnea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties. All scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/QoL represents a high QoL. A high score for a symptom scale/item represents a high level of symptomatology/problems. | at baseline, at month 23 | 
| Change from baseline in EORTC QLQ-C30 role functioning domain score |  | at baseline, at month 23 | 
| Occurrence of treatment-emergent AEs leading to study drug discontinuation during the on-treatment period |  | up to 23 months |