Neuroendocrine Neoplasms
Conditions
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 Part A1, Part A2, and Part B. Part A1 of this study aims to find out the highest dose of BI 764532 that people can tolerate in addition to chemotherapy. Part A2 of this study is to find out how well people tolerate a low dose of BI 764532 combined with the 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.
Interventions
DRUGBI 764532
BI 764532
DRUGCarboplatin
Standard of care
DRUGEtoposide
Standard of care
DRUGCisplatin
Standard of care
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A1: Dose escalation, Part A2: Reduced monitoring, Part B: Dose expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 approximately 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 2 weeks 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 or well differentiated neuroendocrine tumour (NET) stages of the target indication in case of transformed tumors), except for appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A1: Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period | Up to 21 days. |
| Part A2: Reduced monitoring: the occurrence of DLTs during the on-treatment period | Up to 36 months. |
| Part B: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period | Up to 36 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A1: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period | Up to 36 months. | — |
| Part A1: Occurrence of adverse events (AEs) during the on-treatment period | Up to 36 months. | — |
| Part A2: Occurrence of adverse events (AEs) during the on-treatment period | Up to 36 months. | — |
| Part A2: Objective response (OR) | Up to 36 months. | 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. |
| Part B: Objective response (OR) | Up to 36 months. | 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. |
| Part B: Duration of response (DoR) | Up to 36 months. | 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. |
Countries
Belgium, France, Germany, Japan, Netherlands, Spain, Sweden, United States
Contacts
CONTACTBoehringer Ingelheim
Outcome results
None listed