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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

Phase 1
Recruiting
Conditions
Neuroendocrine Neoplasms
Interventions
Registration Number
NCT06132113
Lead Sponsor
Boehringer Ingelheim
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
55
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A: BI 764532 high dose + carboplatin + etoposideBI 764532-
Part A: BI 764532 high dose + carboplatin + etoposideCarboplatin-
Part A: BI 764532 high dose + carboplatin + etoposideEtoposide-
Part B: BI 764532 + carboplatin + etoposideBI 764532-
Part B: BI 764532 + carboplatin + etoposideCarboplatin-
Part B: BI 764532 + carboplatin + etoposideEtoposide-
Part B: BI 764532 + cisplatin + etoposideBI 764532-
Part B: BI 764532 + cisplatin + etoposideEtoposide-
Part B: BI 764532 + cisplatin + etoposideCisplatin-
Part A: BI 764532 low dose + carboplatin + etoposideBI 764532-
Part A: BI 764532 low dose + carboplatin + etoposideCarboplatin-
Part A: BI 764532 low dose + carboplatin + etoposideEtoposide-
Part A: BI 764532 medium dose + carboplatin + etoposideBI 764532-
Part A: BI 764532 medium dose + carboplatin + etoposideCarboplatin-
Part A: BI 764532 medium dose + carboplatin + etoposideEtoposide-
Primary Outcome Measures
NameTimeMethod
Part B: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment periodUp to 36 months.
Part A: Occurrence of dose-limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation periodUp to 21 days.
Secondary Outcome Measures
NameTimeMethod
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.

Part A: Occurrence of dose-limiting toxicities (DLTs) during the on-treatment periodUp to 36 months.
Part A: Occurrence of adverse events (AEs) during the on-treatment periodUp to 36 months.
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.

Trial Locations

Locations (21)

University of Miami

🇺🇸

Miami, Florida, United States

Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Northwestern University

🇺🇸

Chicago, Illinois, United States

John Theurer Cancer Center

🇺🇸

Hackensack, New Jersey, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Brussels - UNIV Saint-Luc

🇧🇪

Bruxelles, Belgium

Edegem - UNIV UZ Antwerpen

🇧🇪

Edegem, Belgium

HOP Louis Pradel

🇫🇷

Bron, France

INS Paoli-Calmettes

🇫🇷

Marseille, France

Klinikum der Universität München AÖR

🇩🇪

München, Germany

Universitätsklinikum Tübingen

🇩🇪

Tübingen, Germany

Aichi Cancer Center Hospital

🇯🇵

Aichi, Nagoya, Japan

National Cancer Center Hospital East

🇯🇵

Chiba, Kashiwa, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Osaka, Japan

National Cancer Center Hospital

🇯🇵

Tokyo, Chuo-ku, Japan

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital La Paz

🇪🇸

Madrid, Spain

Sahlgrenska Universitetsjukhuset

🇸🇪

Göteborg, Sweden

Akademiska hospital

🇸🇪

Uppsala, Sweden

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