Clinical trial NCT06132113: 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
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neuroendocrine Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-11-15
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A: Dose escalation, Part B: Dose expansion
Primary purpose: TREATMENT

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.


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 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 exclusion criteria apply.

Primary outcomes:
measure: Part A: Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period
timeFrame: Up to 21 days.
measure: Part B: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period
timeFrame: Up to 36 months.
Secondary outcomes:
measure: Part A: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment period
timeFrame: Up to 36 months.
measure: Part A: Occurrence of adverse events (AEs) during the on-treatment period
timeFrame: Up to 36 months.
measure: Part B: Objective response (OR)
timeFrame: Up to 36 months.
measure: Part B: Duration of response (DoR)
timeFrame: Up to 36 months.
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Bron
country: France
facility: HOP Louis Pradel
city: Marseille
country: France
facility: INS Paoli-Calmettes
city: München
country: Germany
facility: Klinikum der Universität München AÖR
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset
city: Uppsala
country: Sweden
facility: Akademiska hospital
Study officials:
References: