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RecruitingNCT07544654Updated Sep 29, 2026

DAREON®-NEC-1: A Study in People With Advanced Extrapulmonary Neuroendocrine Cancer (epNEC) to Compare Obrixtamig Plus Carboplatin and Etoposide Treatment With Standard Chemotherapy

A Phase 3 interventional study of Obrixtamig and Carboplatin in Extrapulmonary Neuroendocrine Cancer (epNEC), sponsored by Boehringer Ingelheim. Recruiting at 167 sites in 29 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
390
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is open to adults with advanced extrapulmonary neuroendocrine cancer. The purpose of this study is to find out if a study medicine called obrixtamig plus standard chemotherapy (carboplatin and etoposide) improves survival when compared to standard chemotherapy (carboplatin and etoposide) alone. Obrixtamig is an antibody-like molecule that may help the immune system fight cancer. Another purpose of the study is to test a medical device being developed to measure levels of the tumour marker delta-like ligand 3 (DLL3).

Participants are put into 2 groups randomly, which means by chance. One group (treatment arm) receives obrixtamig and standard chemotherapy followed by obrixtamig alone for up to 3 years. The other group (control arm) receives standard chemotherapy without obrixtamig for about 4 months. All treatments are given as infusions into a vein.

During the study, participants in both groups visit the study site regularly. Participants in the treatment arm stay overnight at the study site following the first 2 obrixtamig treatments. The doctors regularly check participants' health and take note of any unwanted effects. At some of the visits, doctors check the size of the tumour(s). The results are compared between the 2 groups to see whether the treatment works.

02

Conditions studied

  • Extrapulmonary Neuroendocrine Cancer (epNEC)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients with poorly differentiated unresectable locally advanced or metastatic extrapulmonary neuroendocrine carcinoma (epNEC) with Ki-67 >20% or mitotic rate mitotic rate with number of mitoses >20 per 2 mm2, regardless of primary site (including site of unknown origin)
  2. Patients with tumours with mixed histologies are eligible only if neuroendocrine carcinoma component is predominant and represents more than 70% of the overall tumour tissue
  3. No prior systemic treatment for unresectable locally advanced or metastatic epNEC (except for the completed one cycle of standard platinum + etoposide). Prior peri-operative chemotherapy or -radiation for curative intention is allowed if at least 6 months have elapsed between completion of this therapy and diagnosis of unresectable locally advanced or metastatic disease
  4. Patients who have finished one cycle of standard platinum + etoposide regimen as first-line treatment (Cycle 0: etoposide with carboplatin or cisplatin, administered at a minimum dose of cisplatin 75 mg/m2 or carboplatin area under the curve (AUC) 5 and etoposide 80 mg/m2) prior to randomisation
  5. Patients must comply with criteria for receiving further chemotherapy treatment as first-line standard of care (SoC) treatment within 28 days after the start of the initial chemotherapy (Cycle 0)
  6. Adequate archival Formalin-Fixed Paraffin-Embedded (FFPE) tumour tissue, as specified in the Laboratory Manual, must be available for central laboratory analysis of Delta-like ligand 3 (DLL3) expression status. Tumours must be positive (as defined in the diagnostic study protocol) for DLL3 expression status assessed by investigational VENTANA DLL3 (SP347) RxDx Assay
  7. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  8. 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) Further inclusion criteria apply.

Exclusion criteria

Exclusion Criteria:

  1. Presence of leptomeningeal disease and/or carcinomatous meningitis
  2. Patients with diagnosis of Merkel cell carcinoma or medullary thyroid carcinoma
  3. Patients with neuroendocrine prostate cancer
  4. Patients with well-differentiated neuroendocrine tumours of any grade according to the world health organization (WHO) classification, 5th edition
  5. Patients with a history of well differentiated Neuroendocrine tumour (NET) tumour that transformed into poorly differentiated Neuroendocrine carcinoma (NEC)
  6. Previous treatment with obrixtamig or other DLL3-targeting therapies (e.g. T-cell engager (TcEs), cell therapies, antibody-drug conjugates, or radiopharmaceuticals)
  7. Previous treatment with anti-PD-1 or programmed death ligand 1 (PD-L1) therapies during the one cycle of standard platinum + etoposide first-line chemotherapy (Cycle 0)
  8. Toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or grade prior to Cycle 0. Participants with alopecia any grade, CTCAE ≤Grade 2 asthenia/fatigue, amenorrhea/menstrual disorders any grade, CTCAE ≤Grade 2 peripheral neuropathy, and/or CTCAE ≤Grade 2 endocrinopathies controlled by replacement therapy, and toxicities, which are considered irreversible but stable for at least 4 weeks, per Investigator judgement may be eligible Further exclusion criteria apply.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
390 participants (estimated)

Study arms

  • Experimental
    Obrixtamig + carboplatin + etoposide

    Treatment arm

    Drug: Obrixtamig · Drug: Carboplatin · Drug: Etoposide · Device: Ventana DLL3 RxDx assay

  • Active comparator
    Carboplatin + etoposide

    Control arm

    Drug: Carboplatin · Drug: Etoposide · Device: Ventana DLL3 RxDx assay

Interventions

  • DrugObrixtamig

    Obrixtamig

  • DrugCarboplatin

    Carboplatin

  • DrugEtoposide

    Etoposide

  • DeviceVentana DLL3 RxDx assay

    Ventana DLL3 RxDx assay

05

What researchers measure

Primary outcomes

  1. Overall survival (OS)

    defined as the time from randomisation until death from any cause

    Time frame: Up to 38 months

Secondary outcomes

  1. Progression-free survival (PFS)

    defined as the time from randomisation until the earliest date of disease progression according to RECIST 1.1 based on investigator assessments or death from any cause, whichever occurs first

    Time frame: Up to 38 months

  2. Change from baseline to Week 19 in the physical functioning domain of the EORTC QLQ-C30

    European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) includes 1 global health status/QoL scale, 5 functional scales, 3 symptoms scales and 6 single items to assess dyspnea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties. Each score 0-100. Global health status higher = better, functional scale higher = better, symptom scale higher = worse

    Time frame: At baseline, up to week 19

  3. Objective response (OR)

    defined as a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 (based on investigator assessments) from randomisation until the earliest date of disease progression, death, last evaluable tumour assessment before the start of next line of anti-cancer treatment, loss to follow-up, or withdrawal of consent

    Time frame: Up to 38 months

  4. Duration of response (DoR)

    defined as the time from the first documented OR according to RECIST 1.1 until the earliest date of disease progression or death among patients with objective response based on investigator assessments

    Time frame: Up to 38 months

  5. Disease control (DC)

    defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST 1.1 based on investigator assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of next line of anti-cancer treatment, loss to follow-up or withdrawal of consent

    Time frame: Up to 38 months

  6. Occurrence of treatment-emergent Grade 3 or greater Cytokine release syndrome (CRS)

    Time frame: Up to 38 months

  7. Occurrence of treatment-emergent Grade 3 or greater Immune cell associated neurotoxicity syndrome (ICANS)

    Time frame: Up to 38 months

  8. Occurrence of treatment-emergent adverse events (AEs) leading to permanent discontinuation of trial medication during the on-treatment period

    Time frame: Up to 38 months

  9. Occurrence of treatment-emergent AEs leading to dose modification of trial medication (i.e. dose interruption, dose delay, dose reduction)

    Time frame: Up to 38 months

06

Study locations

60 of 167 sites recruiting
  • Mayo Clinic
    Scottsdale, Arizona 85259, United States
    Not yet recruiting
  • City of Hope-Duarte-56419
    Duarte, California 91010, United States
    Recruiting
  • University of California San Francisco
    San Francisco, California 94158, United States
    Not yet recruiting
  • University of California Los Angeles
    Santa Monica, California 90404, United States
    Not yet recruiting
  • Mayo Clinic - Florida
    Jacksonville, Florida 32224, United States
    Not yet recruiting
  • Emory University
    Atlanta, Georgia 30322, United States
    Recruiting
  • The University of Chicago Medical Center
    Chicago, Illinois 60637, United States
    Not yet recruiting
  • The Skip Viragh Outpatient Cancer Research Building
    Baltimore, Maryland 21287, United States
    Not yet recruiting
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Not yet recruiting
  • Mayo Clinic, Rochester
    Rochester, Minnesota 55905, United States
    Not yet recruiting
  • Washington University School of Medicine
    St Louis, Missouri 63108, United States
    Recruiting
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10022, United States
    Not yet recruiting
  • The Ohio State University Wexner Medical Center
    Columbus, Ohio 43221, United States
    Not yet recruiting
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15232, United States
    Not yet recruiting
  • University of Tennessee
    Knoxville, Tennessee 37920, United States
    Recruiting
  • SCRI Oncology Partners
    Nashville, Tennessee 37203, United States
    Recruiting
  • Vanderbilt-Ingram Cancer Center
    Nashville, Tennessee 37232, United States
    Not yet recruiting
  • Baylor University Medical Center
    Dallas, Texas 75246, United States
    Not yet recruiting
  • The University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
    Not yet recruiting
  • Huntsman Cancer Institute
    Salt Lake City, Utah 84112, United States
    Not yet recruiting
  • Fred Hutchinson Cancer Research Center
    Seattle, Washington 98109, United States
    Not yet recruiting
  • Centro Medico Reumatologico - OMI
    CABA, 1015, Argentina
    Recruiting
  • Hospital Britanico de Buenos Aires
    CABA, 1280AEB, Argentina
    Recruiting
  • Clinica Privada Independencia
    Munro, B1605, Argentina
    Recruiting
  • Sanatorio Parque S.A.
    Rosario, S2000DSV, Argentina
    Recruiting
  • Royal North Shore Hospital
    St Leonards, New South Wales 2065, Australia
    Not yet recruiting
  • Flinders Medical Centre
    Bedford Park, South Australia 5042, Australia
    Recruiting
  • Peter MacCallum Cancer Centre
    Melbourne, Victoria 3000, Australia
    Recruiting
  • Fiona Stanley Hospital
    Murdoch, Western Australia 6150, Australia
    Recruiting
  • Medical University of Graz
    Graz, 8036, Austria
    Not yet recruiting
  • Medical University of Vienna
    Vienna, 1090, Austria
    Not yet recruiting
  • Cliniques Universitaires Saint-Luc
    Brussels, 1200, Belgium
    Recruiting
  • Universitair Ziekenhuis Antwerpen
    Edegem, 2650, Belgium
    Recruiting
  • UZ Leuven
    Leuven, 3000, Belgium
    Recruiting
  • Centre Hospitalier Universitaire de Liège
    Liège, 4000, Belgium
    Recruiting
  • Hospital de Amor
    Barretos, 14784-400, Brazil
    Recruiting
  • Instituto D'Or de Pesquisa E Ensino - Pe
    Recife, 50070-480, Brazil
    Not yet recruiting
  • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
    São José do Rio Preto, 15090-000, Brazil
    Recruiting
  • ICESP - Instituto do Cancer do Estado de Sao Paulo
    São Paulo, 01246-000, Brazil
    Not yet recruiting
  • A.C. Camargo
    São Paulo, 01509-010, Brazil
    Not yet recruiting
  • Sunnybrook Health Sciences Centre
    Toronto, Ontario M4N 3M5, Canada
    Recruiting
  • Instituto Oncologico FALP
    Providencia, Chile
    Not yet recruiting
  • Bradford Hill- Centro de Investigacion Clinica
    Recoleta, 8420383, Chile
    Not yet recruiting
  • Clinica Alemana de Santiago S.A.
    Santiago, 7650568, Chile
    Not yet recruiting
  • Beijing Cancer Hospital
    Beijing, 100142, China
    Recruiting
  • Beijing GoBroad Hospital
    Beijing, 102200, China
    Recruiting
  • The First Hospital of Jilin University
    Changchun, 130021, China
    Not yet recruiting
  • Xiangya Hospital, Central South University
    Changsha, 410008, China
    Not yet recruiting
  • Hunan Province Tumor Hospital
    Changsha, 410013, China
    Not yet recruiting
  • Sichuan Cancer Hospital
    Chengdu, 610041, China
    Recruiting
  • West China Hospital, Sichuan University
    Chengdu, 610041, China
    Recruiting
  • Chongqing University Affiliated Cancer Hospital
    Chongqing, 400000, China
    Recruiting
  • Fujian Cancer Hospital
    Fuzhou, 350014, China
    Not yet recruiting
  • The First Affiliated Hospital,Sun Yat-sen University
    Guangzhou, 510080, China
    Recruiting
  • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
    Hangzhou, 310016, China
    Recruiting
  • Harbin Medical University Cancer Hospital
    Harbin, 150081, China
    Recruiting
  • Qilu Hospital, Shangdong University
    Jinan, 250012, China
    Recruiting
  • Shandong Cancer Hospital
    Jinan, 250117, China
    Recruiting
  • Linyi Cancer Hospital
    Linyi, 276034, China
    Recruiting
  • The First Affiliated Hospital of Henan University of Science and Technology
    Luoyang, 471003, China
    Recruiting
  • The Affiliated Cancer Hospital, Guangxi Medical University
    Nanning, 530021, China
    Recruiting
  • Shanghai General Hospital
    Shanghai, 200080, China
    Recruiting
  • Hubei Cancer Hospital
    Wuhan, 430000, China
    Recruiting
  • First Affiliated Hospital of Xi'an JiaoTong University
    Xi'an, 710061, China
    Not yet recruiting
  • First Affiliated Hospital of Xiamen University
    Xiamen, 361003, China
    Not yet recruiting
  • The First Affiliated Hospital of Zhengzhou University
    Zhengzhou, 450052, China
    Not yet recruiting
  • Masaryk Memorial Cancer Institute
    Brno, 65653, Czechia
    Not yet recruiting
  • University Hospital Hradec Kralove (FNHK)
    Hradec Králové, 50005, Czechia
    Not yet recruiting
  • Aarhus University Hospital
    Aarhus N, 8200, Denmark
    Not yet recruiting
  • Rigshospitalet
    Copenhagen, 2100, Denmark
    Not yet recruiting
  • Odense University Hospital
    Odense C, 5000, Denmark
    Not yet recruiting
  • Helsinki University Hospital
    Helsinki, 00290, Finland
    Not yet recruiting
  • KYS Sädesairaala
    Kuopio, 70029, Finland
    Not yet recruiting
  • Tampere University Hospital
    Tampere, 33520, Finland
    Not yet recruiting
  • Turku University Hospital / TYKS
    Turku, 20520, Finland
    Not yet recruiting
  • Hôpital Beaujon
    Clichy, 92110, France
    Recruiting
  • HOP François Mitterrand
    Dijon, 21000, France
    Recruiting
  • Hôpital Edouard Herriot
    Lyon, 69437, France
    Not yet recruiting
  • INS Paoli-Calmettes
    Marseille, 13009, France
    Not yet recruiting
  • HOP Haut-Lévêque
    Pessac, 33604, France
    Not yet recruiting
  • CTR Eugène Marquis
    Rennes, 35042, France
    Not yet recruiting
  • Hôpital Rangueil - CHU de Toulouse
    Toulouse, 31059, France
    Not yet recruiting
  • Institut Gustave Roussy
    Villejuif, 94800, France
    Recruiting
  • DRK Kliniken Berlin Köpenick
    Berlin, 12559, Germany
    Not yet recruiting
  • Universitätsklinikum Bonn AöR
    Bonn, 53127, Germany
    Not yet recruiting
  • Universitätsklinikum Köln (AöR)
    Cologne, 50937, Germany
    Not yet recruiting
  • Technische Universität Dresden
    Dresden, 01307, Germany
    Not yet recruiting
  • Universitätsklinikum Düsseldorf
    Düsseldorf, 40225, Germany
    Not yet recruiting
  • Universitätsklinikum Erlangen
    Erlangen, 91054, Germany
    Not yet recruiting
  • Universitätsklinikum Freiburg
    Freiburg im Breisgau, 79106, Germany
    Not yet recruiting
  • Asklepios Klinik St Georg
    Hamburg, 20099, Germany
    Not yet recruiting
  • Universitätsklinikum Heidelberg
    Heidelberg, 69120, Germany
    Recruiting
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    Mainz, 55131, Germany
    Not yet recruiting
  • Westfälische Wilhelms-Universität Münster
    Münster, 48149, Germany
    Not yet recruiting
  • Universitätsklinikum Tübingen
    Tübingen, 72076, Germany
    Not yet recruiting
  • Universitätsklinikum Würzburg AÖR
    Würzburg, 97078, Germany
    Not yet recruiting
  • Prince of Wales Hospital-Hong Kong-20715
    Hong Kong, 999077, Hong Kong
    Recruiting
  • Queen Mary Hospital
    Hong Kong, 999077, Hong Kong
    Recruiting
  • Soroka Univ. Medical Center
    Beersheba, 84101, Israel
    Not yet recruiting
  • Rambam Health Care Campus
    Haifa, 3109601, Israel
    Not yet recruiting

Showing the first 100 of 167 sites across 29 countries.

07

References and documents

Related links

Individual participant data

Plan to share: Yes — Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.clinicalstudies.boehringer-ingelheim.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

Supporting information: Study protocol, Sap, Csr

08

Registry details

Key details

Study ID
NCT07544654
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Apr 22, 2026
Start date
Jul 10, 2026
Primary completion
Dec 13, 2029 (estimated)
Completion
Mar 11, 2031 (estimated)
Last update
Sep 29, 2026

Study contacts

Boehringer Ingelheim
Contact
clintriage.rdg@boehringer-ingelheim.com
1-800-243-012

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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