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NCT05882058PHASE2Recruiting

DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers

Boehringer Ingelheim

Start Date

10/13/2023

Completion Date

6/8/2028

Summary

This study is open to adults with small cell lung cancer and other neuroendocrine tumours. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find a suitable dose of BI 764532 (also called obrixtamig) that people with advanced cancer can tolerate. 2 different doses of BI 764532 are tested in this study. Another purpose is to check whether BI 764532 can make tumours shrink. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. The study has 3 parts. In Part 1, participants are put into 2 groups randomly, which means by chance. Participants have an equal chance of being in either group. One group gets dose 1 of BI 764532 and the other group gets dose 2 of BI 764532. In Part 2 and Part 3, all participants receive the same dose of BI 764532. Part 2 and Part 3 are open to people with a certain kind of tumour called extrapulmonary neuroendocrine carcinoma. All participants receive BI 764532 as an infusion into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include an overnight stay to monitor participants´ safety. Doctors record any unwanted effects and regularly check the general health of the participants.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion criteria: 1. 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). 2. Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. 3. Part 1: Histologically or cytologically confirmed, cancer of the following histologies: * Small cell lung cancer (SCLC) * Extra-pulmonary neuroendocrine carcinoma (epNEC) (except Merkel cell carcinoma (MCC), Medullary thyroid cancer (MTC) and Neuroendocrine prostate cancer (NEPC)) * Large cell neuroendocrine carcinoma (LCNEC) of the lung Patients with tumours with mixed histologies for any above type are eligible only if the neuroendocrine carcinoma/small tumour cells component is predominant and represents at least 50% of the overall tumour tissue. Patients must have progressed or recurred after standard of care therapy * SCLC: after at least two prior lines of therapy, including at least one platinum-based regimen; in countries where standard of care in first line therapy includes PD-L1 inhibitor treatment patients should have received the combination of platinum-based regimen plus PD-L1 inhibitor unless they have been unable to receive checkpoint inhibitor treatment. * Therapy includes PD-L1 inhibitor treatment; patients should have received the combination of platinum-based regimen plus PD-L1 inhibitor unless they have been unable to receive checkpoint inhibitor treatment. * epNEC/LCNEC: after at least one platinum-based regimen. Part 2 and part 3: Histologically or cytologically confirmed epNEC (except MCC, MTC and NEPC) with centrally assessed DLL3 high expression status. Patients must have progressed or recurred after at least one platinum-based regimen. 4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1., 5. Measurable lesions as defined per Response Evaluation Criteria In Solid Tumours (RECIST) v 1.1 within 21 days prior to the first dose of BI 764532. 6. Part 1: Availability of archival tumour tissue sample Part 2 and part 3: Availability of archival formalin-fixed paraffin-embedded (FFPE) tumour tissue sample. Following specimens are not allowed: Fine Needle Aspiration (FNA), Cytology samples, decalcified bone samples. 7. Adequate organ function as defined in the protocol. 8. All toxicities related to previous anti-cancer therapies have resolved = Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to trial treatment administration (except for alopecia, peripheral neuropathy, fatigue and endocrinopathies controlled by replacement therapy which must be = CTCAE Grade 2 and amenorrhea/menstrual disorders which can be any grade). 9. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information 10. Only for Part 3, at the timepoint of Screening 02: * For Cycle 1, patients should be willing to stay within 1 hour driving distance for 48 hours after IMP administration and confirm availability of a caregiver for the same timeframe. * Patients should be considered suitable by the investigator to follow instructions applicable to the reduced monitoring cohort, such as taking their temperature and administration of oral medication at home if needed. Exclusion criteria: 1. Untreated or symptomatic brain metastases. (Part 2 and part 3: identified during the mandatory assessment by brain MRI within 21 days before first trial drug administration.) Participants with treated, stable brain metastases are eligible provided they meet the following criteria: * Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to the first administration of BI 764532. * Patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off anti-epileptic drugs for at least 7 days or on stable doses of anti-epileptic drugs for malignant central nervous system (CNS) disease. 2. Presence of leptomeningeal disease or, part 2 and part 3: epidural disease including spinal cord compression. 3. Part 1: Active/previous history of interstitial lung disease or non-infectious pneumonitis (any grade). Part 2 and part 3: Active/previous history of interstitial lung disease, pulmonary fibrosis, organizing pneumonia or non-infectious pneumonitis (any grade). Patients with a history of therapy-related pneumonitis that is considered clinically resolved are eligible. 4. Participants who experienced severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents. 5. Prior anti-cancer therapy: * Patients who have been treated with any other anti-cancer drug within 4 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 764532. * Patients who have been treated with extensive field radiotherapy including whole brain irradiation within 2 weeks prior to first administration of BI 764532. 6. Previous treatment with Delta-like ligand 3 (DLL3)-targeting T cell engagers or cell therapies. 7. Diagnosis of immunodeficiency or systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of BI 764532. Physiological replacement of steroids is allowed. 8. Unresolved toxicity from prior anti-tumour therapy, defined in the inclusion criteria. Further exclusion criteria apply.

Interventions

DRUG

BI 764532, dose 1

DRUG

BI 764532, dose 2

DEVICE

Ventana DLL3 RxDx assay

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Conditions

Small Cell Lung CarcinomaNeuroendocrine NeoplasmsExtra-pulmonary Neuroendocrine Carcinoma

Locations

Infirmary Cancer Care

Mobile, Alabama 36607

United States

Mayo Clinic-Arizona

Phoenix, Arizona 85054

United States

Valkyrie Clinical Trials

Los Angeles, California 90067

United States

University of California San Francisco

San Francisco, California 94143

United States

Mayo Clinic Cancer Center

Jacksonville, Florida 32224

United States

University of Miami

Miami, Florida 33136

United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida 33612

United States

Indiana University

Indianapolis, Indiana 46202

United States

University of Kansas Cancer Center

Westwood, Kansas 66205

United States

University of Kentucky Medical Center

Lexington, Kentucky 40536

United States

University of Maryland School of Medicine

Baltimore, Maryland 21201

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Mayo Clinic, Rochester

Rochester, Minnesota 55905

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

Montefiore Medical Center

The Bronx, New York 10461

United States

Virginia Commonwealth University Health- Adult Outpatient Pavilion

Richmond, Virginia 23219

United States

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

UZ Leuven

Leuven, 3000

Belgium

Multiprofile Hospital For Active Treatment-Uni Hospital Ltd.

Panagyurishte, 4500

Bulgaria

MHAT Heart and brain

Pleven, 5804

Bulgaria

West China Hospital, Sichuan University

Chengdu, 610041

China

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

Hangzhou, 310016

China

Qilu Hospital, Shangdong University

Jinan, 250012

China

960 Hospital of the Chinese People's Liberation Army

Jinan, 250031

China

The Second Affiliated Hospital to Nanchang University

Nanchang, 330006

China

Shanghai Chest Hospital

Shanghai, 200030

China

HOP Intercommunal

Créteil, 94000

France

Hôpital Cochin

Paris, 75014

France

HOP Civil

Strasbourg, 67091

France

Evangelische Lungenklinik Berlin

Berlin, 13125

Germany

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307

Germany

Universitätsklinikum Erlangen

Erlangen, 91054

Germany

Asklepios Fachkliniken München-Gauting

Gauting, 82131

Germany

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927

Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131

Germany

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681

Japan

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577

Japan

Sendai Kousei Hospital

Miyagi, Sendai, 981-0914

Japan

Osaka International Cancer Institute

Osaka, Osaka, 541-8567

Japan

Kindai University Hospital

Osaka, Sakai, 590-0197

Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045

Japan

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550

Japan

Hospital CUF Descobertas-Lisboa-69316

Lisbon, 1350-352

Portugal

Hospital CUF Porto

Porto, 4100-180

Portugal

Severance Hospital

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital del Mar

Barcelona, 08003

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario Virgen de la Victoria

Málaga, 29010

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain

NCKUH

Tainan, 704

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan County, 333

Taiwan

Leicester Royal Infirmary

Leicester, LE1 5WW

United Kingdom

University College Hospital

London, WC1E 6AG

United Kingdom

The Christie Hospital

Manchester, M20 4BX

United Kingdom

Freeman Hospital

Newcastle upon Tyne, NE7 7DN

United Kingdom