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NCT07544654PHASE3Recruiting

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

Boehringer Ingelheim

Start Date

7/10/2026

Completion Date

3/11/2031

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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: 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.

Interventions

DRUG

Obrixtamig

DRUG

Carboplatin

DRUG

Etoposide

DEVICE

Ventana DLL3 RxDx assay

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Conditions

Extrapulmonary Neuroendocrine Cancer (epNEC)

Locations

Mayo Clinic

Scottsdale, Arizona 85259

United States

City of Hope-Duarte-56419

Duarte, California 91010

United States

Stanford Cancer Center

Palo Alto, California 94304

United States

University of California San Francisco

San Francisco, California 94158

United States

University of California Los Angeles

Santa Monica, California 90404

United States

Mayo Clinic - Florida

Jacksonville, Florida 32224

United States

Emory University

Atlanta, Georgia 30322

United States

The Skip Viragh Outpatient Cancer Research Building

Baltimore, Maryland 21287

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Mayo Clinic, Rochester

Rochester, Minnesota 55905

United States

Washington University School of Medicine

St Louis, Missouri 63108

United States

Memorial Sloan-Kettering Cancer Center

New York, New York 10022

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania 15232

United States

University of Tennessee

Knoxville, Tennessee 37920

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee 37232

United States

Baylor University Medical Center

Dallas, Texas 75246

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

Huntsman Cancer Institute

Salt Lake City, Utah 84112

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109

United States

Centro Medico Reumatologico - OMI

CABA, 1015

Argentina

Hospital Britanico de Buenos Aires

CABA, 1280AEB

Argentina

Clinica Privada Independencia

Munro, B1605

Argentina

Sanatorio Parque S.A.

Rosario, S2000DSV

Argentina

Royal North Shore Hospital

St Leonards, New South Wales 2065

Australia

Flinders Medical Centre

Bedford Park, South Australia 5042

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Fiona Stanley Hospital

Murdoch, Western Australia 6150

Australia

Medical University of Graz

Graz, 8036

Austria

AKH - Medical University of Vienna

Vienna, 1090

Austria

Cliniques Universitaires Saint-Luc

Brussels, 1200

Belgium

Universitair Ziekenhuis Antwerpen

Edegem, 2650

Belgium

UZ Leuven

Leuven, 3000

Belgium

Centre Hospitalier Universitaire de Liège

Liège, 4000

Belgium

Hospital de Amor

Barretos, 14784-400

Brazil

Instituto D'Or de Pesquisa E Ensino - Pe

Recife, 50070-480

Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

São José do Rio Preto, 15090-000

Brazil

ICESP - Instituto do Cancer do Estado de Sao Paulo

São Paulo, 01246-000

Brazil

A.C. Camargo

São Paulo, 01509-010

Brazil

Sunnybrook Health Sciences Centre

Toronto, Ontario M4N 3M5

Canada

Instituto Oncológico FALP

Providencia,

Chile

Bradford Hill- Centro de Investigación Clínica

Recoleta, 8420383

Chile

Clínica Alemana de Santiago S.A.

Santiago, 7650568

Chile

Beijing Cancer Hospital

Beijing, 100142

China

Beijing GoBroad Hospital

Beijing, 102200

China

The First Hospital of Jilin University

Changchun, 130021

China

Xiangya Hospital, Central South University

Changsha, 410008

China

Hunan Province Tumor Hospital

Changsha, 410013

China

Sichuan Cancer Hospital

Chengdu, 610041

China

West China Hospital, Sichuan University

Chengdu, 610041

China

Chongqing University Affiliated Cancer Hospital

Chongqing, 400000

China

Fujian Cancer Hospital

Fuzhou, 350014

China

The First Affiliated Hospital,Sun Yat-sen University

Guangzhou, 510080

China

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Hangzhou, 310016

China

Harbin Medical University Cancer Hospital

Harbin, 150081

China

Qilu Hospital, Shangdong University

Jinan, 250012

China

Shandong Cancer Hospital

Jinan, 250117

China

Linyi Cancer Hospital

Linyi, 276034

China

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, 471003

China

The Affiliated Cancer Hospital, Guangxi Medical University

Nanning, 530021

China

Shanghai General Hospital

Shanghai, 200080

China

Hubei Cancer Hospital

Wuhan, 430000

China

First Affiliated Hospital of Xi'an JiaoTong University

Xi'an, 710061

China

First Affiliated Hospital of Xiamen University

Xiamen, 361003

China

Henan Cancer Hospital

Zhengzhou, 450003

China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052

China

Masaryk Memorial Cancer Institute

Brno, 65653

Czechia

University Hospital Hradec Kralove (FNHK)

Hradec Králové, 50005

Czechia

Aarhus University Hospital

Aarhus N, 8200

Denmark

Rigshospitalet

Copenhagen, 2100

Denmark

Odense University Hospital

Odense C, 5000

Denmark

Helsinki University Hospital

Helsinki, 00290

Finland

KYS Sädesairaala

Kuopio, 70029

Finland

Tampere University Hospital

Tampere, 33520

Finland

Turku University Hospital / TYKS

Turku, 20520

Finland

Hôpital Beaujon

Clichy, 92110

France

HOP François Mitterrand

Dijon, 21000

France

Hôpital Edouard Herriot

Lyon, 69437

France

INS Paoli-Calmettes

Marseille, 13009

France

HOP Haut-Lévêque

Pessac, 33604

France

CTR Eugène Marquis

Rennes, 35042

France

Hôpital Rangueil - CHU de Toulouse

Toulouse, 31059

France

Institut Gustave Roussy

Villejuif, 94800

France

DRK Kliniken Berlin Köpenick

Berlin, 12559

Germany

Universitätsklinikum Bonn AöR

Bonn, 53127

Germany

Universitätsklinikum Köln (AöR)

Cologne, 50937

Germany

Technische Universität Dresden

Dresden, 01307

Germany

Universitätsklinikum Düsseldorf

Düsseldorf, 40225

Germany

Universitätsklinikum Erlangen

Erlangen, 91054

Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106

Germany

Asklepios Klinik St Georg

Hamburg, 20099

Germany

Universitätsklinikum Heidelberg

Heidelberg, 69120

Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131

Germany

Westfälische Wilhelms-Universität Münster

Münster, 48149

Germany

Universitätsklinikum Tübingen

Tübingen, 72076

Germany

Universitätsklinikum Würzburg AÖR

Würzburg, 97078

Germany

Prince of Wales Hospital-Hong Kong-20715

Hong Kong, 999077

Hong Kong

Queen Mary Hospital

Hong Kong, 999077

Hong Kong

Soroka Univ. Medical Center

Beersheba, 84101

Israel

Rambam Health Care Campus

Haifa, 3109601

Israel

Hadassah Medical Center, Ein-Karem

Jerusalem, 9112001

Israel

Sourasky Medical Center

Tel Aviv, 6093246

Israel

Azienda Universitaria Ospedaliera Consorziale Policlinico Bari

Bari, 70124

Italy

A. O. Universitaria Careggi

Florence, 50134

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Naples, 80131

Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, 90129

Italy

Fondazione Policlinico Universitario Campus Bio-medico

Roma, 00128

Italy

Centro Ricerche Cliniche di Verona S.r.l.

Verona, 37134

Italy

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681

Japan

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577

Japan

Shikoku Cancer Center

Ehime, Matsuyama, 791-0280

Japan

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582

Japan

Hokkaido University Hospital

Hokkaido, Sapporo, 060-8648

Japan

Kanazawa University Hospital

Ishikawa, Kanazawa, 920-8641

Japan

Kanagawa Cancer Center

Kanagawa, Yokohama, 241-8515

Japan

Kyoto University Hospital

Kyoto, Kyoto, 606-8507

Japan

Tohoku University Hospital

Miyagi, Sendai, 980-8574

Japan

Okayama University Hospital

Okayama, Okayama, 700-8558

Japan

Osaka International Cancer Institute

Osaka, Osaka, 541-8567

Japan

Shizuoka Cancer Center

Shizuoka, Sunto-gun, 411-8777

Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045

Japan

Health Pharma Professional Research S.A. de C.V.

Mexico City, 03100

Mexico

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Amsterdam (METC AVL)

Amsterdam, 1066CX

Netherlands

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ

Netherlands

Maastricht University Medisch Centrum

Maastricht, 6229 HX

Netherlands

Erasmus Medisch Centrum

Rotterdam, 3015 GD

Netherlands

Auckland City Hospital

Grafton / Auckland, 1023

New Zealand

Haukeland Universitetssykehus

Bergen, 5021

Norway

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, N-0379

Norway

Helse Stavanger, Stavanger Universitetssykehus

Stavanger, 4011

Norway

St. Olavs Hospital, Universitetssykehuset i Trondheim

Trondheim, 7030

Norway

Medical University Gdansk

Gdansk, 80-214

Poland

Silesian Medical University in Katowice

Katowice, 40514

Poland

IPO Lisboa Francisco Gentil, EPE

Lisbon, 1099-023

Portugal

Hospital Lusíadas Lisboa

Lisbon, 1500-458

Portugal

Unidade Local de Saúde Santa Maria

Lisbon, 1699-035

Portugal

Hospital CUF Porto

Porto, 4100-180

Portugal

IPO Porto Francisco Gentil, EPE

Porto, 4200-072

Portugal

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Institut Català d'Oncologia de Badalona

Badalona, 8916

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario Ramon Y Cajal

Madrid, 28034

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Regional Universitario de Málaga

Málaga, 29010

Spain

Complejo Hospitalario de Navarra

Pamplona, 31008

Spain

Hospital Universitario Marqués de Valdecilla

Santander, 39008

Spain

Hospital Virgen del Rocío

Seville, 41013

Spain

Hospital Clinico De Valencia (INCLIVA)

Valencia, 46010

Spain

Sahlgrenska Universitetsjukhuset

Gothenburg, 41345

Sweden

Skånes universitetssjukhus

Lund, 22185

Sweden

Uppsala University Hospital

Uppsala, 751 85

Sweden

National Cheng Kung University Hospital

Tainan, 70403

Taiwan

Taipei Veterans General Hospital

Taipei, 112201

Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan City, 333

Taiwan

Addenbrooke's Hospital

Cambridge, CB2 0QQ

United Kingdom

Western General Hospital

Edinburgh, EH4 2XU

United Kingdom

Guy's Hospital

London, SE1 9RT

United Kingdom

The Christie Hospital

Manchester, M20 4BX

United Kingdom