DAREON™-7: A Study to Test How Well Different Doses of BI 764532 in Addition to Chemotherapy Are Tolerated by People With Advanced Neuroendocrine Cancers

Study Overview
=================
Brief Summary
-----------------
This study is open to adults aged 18 and older or above legal age who have a specific type of advanced neuroendocrine cancer (NEC). Their tumours must be positive for a marker called DLL3. The purpose of this study is to test a medicine called BI 764532 in addition to chemotherapy. The study has 2 parts. Part A of this study aims to find out the highest dose of BI 764532 that people can tolerate in addition to chemotherapy. The purpose of Part B is to find out how well people can tolerate BI 764532 in combination with different chemotherapies. Researchers also want to find out whether BI 764532 in combination with chemotherapy helps people with NEC. Participants get different doses of BI 764532 as an infusion into a vein. In addition, they get platinum-based chemotherapy as infusions into a vein. Participants can continue treatment up to 3 years if they benefit from treatment and can tolerate it. Participants visit their doctors regularly. During these visits, the doctors collect information about participants' health and take note of any unwanted effects. Doctors also regularly check the size of the tumour.

Official Title
-----------------
DAREON™-7: A Phase I, Open-label, Dose Escalation and Expansion Trial to Investigate Safety and Tolerability of BI 764532 Intravenous Infusions in Combination With Standard of Care (Platinum and Etoposide) in First-line Treatment of Patients With Neuroendocrine Carcinomas (NEC)

Conditions
-----------------
Neuroendocrine Neoplasms

Intervention / Treatment
-----------------
* Drug: BI 764532
* Drug: Carboplatin
* Drug: Etoposide
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
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 ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses Patients diagnosed with locally advanced or metastatic NEC of following subtypes: extrapulmonary neuroendocrine carcinomas (epNEC) pulmonary large cell NEC (LCNEC) neuroendocrine carcinomas (NEC) of unknown primary site Patients with tumours with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumour cells component is predominant and represent at least 50% of the overall tumour tissue Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Minimum life expectancy of 12 weeks At least one measurable lesion as defined per RECIST 1.1 within 35 days prior to the first dose of BI 764532 Patients with a history of asymptomatic Central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: No radiotherapy (including whole brain radiation therapy, stereotactic radiotherapy or radiosurgery) within 7 days Are neurologically stable without the need for steroids or anti-convulsants for at least 7 days before first dose of BI 764532 as per local site assessment 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) Patients with diagnosis of Merkel cell carcinoma or medullary thyroid carcinoma or Grade 3 neuroendocrine tumour Presence of leptomeningeal carcinomatosis Previous treatment with 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 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part A: Dose escalation, Part B: Dose expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: BI 764532 low dose + carboplatin + etoposide<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Standard of care<br>Drug: Etoposide<br>* Standard of care<br>|
| Experimental: Part A: BI 764532 medium dose + carboplatin + etoposide<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Standard of care<br>Drug: Etoposide<br>* Standard of care<br>|
| Experimental: Part A: BI 764532 high dose + carboplatin + etoposide<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Standard of care<br>Drug: Etoposide<br>* Standard of care<br>|
| Experimental: Part B: BI 764532 + carboplatin + etoposide<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Carboplatin<br>* Standard of care<br>Drug: Etoposide<br>* Standard of care<br>|
| Experimental: Part B: BI 764532 + cisplatin + etoposide<br> | Drug: BI 764532<br>* BI 764532<br>Drug: Etoposide<br>* Standard of care<br>Drug: Cisplatin<br>* Standard of care<br>|

What is the study measuring?
-----------------
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 21 days. | 
| Part B: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period |  | Up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period |  | Up to 36 months. | 
| Part A: Occurrence of adverse events (AEs) during the on-treatment period |  | Up to 36 months. | 
| Part B: Objective response (OR) | Objective response (OR), 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 36 months. | 
| Part B: Duration of response (DoR) | Duration of response (DoR), 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 36 months. |