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

NCT05882058 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 1438-00052023-504247-13-00U1111-1292-4406
• Study Type: interventional
• Target: 204
• Locations: 12 countries
• Sites: 59

Brief 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.

Conditions

Small Cell Lung Carcinoma; Neuroendocrine Neoplasms; Extra-pulmonary Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (5)

• Part 1: Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR)

  according to RECIST v 1.1 by investigator 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.

  up to 26 months

• Part 1: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period

  up to 26 months

• Part 2: Objective response (OR)

  Objective response is defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v 1.1 by blinded independent central review 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

  up to 27 months

• Part 3: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period

  up to 23 months

• Part 3: Objective response (OR) by blinded independent central review

  up to 23 months

Secondary Outcomes (11)

• Part 1: Duration of objective response (DOR) based on investigator assessment

  up to 26 months

• Part 1: Progression-free survival (PFS) based on investigator assessment

  up to 26 months

• Part 1: Disease control (DC), defined as best overall response of CR or PR or stable disease (SD) based on investigator assessment

  up to 26 months

• Part 1, 2, and 3: Overall survival (OS), defined as the time from treatment start until death from any cause

  up to 26 months

• Part 1, 2, and 3: Change from baseline in EORTC QLQ-C30 physical functioning domain score

  at baseline, at month 26

Study Arms (4)

Part 1: Dose group 1

EXPERIMENTAL

Drug: BI 764532, dose 1

Part 1: Dose group 2

EXPERIMENTAL

Drug: BI 764532, dose 2

Part 2: Expansion cohort

EXPERIMENTAL

Drug: BI 764532, dose 1

Part 3: Expansion cohort

EXPERIMENTAL

Drug: BI 764532, dose 1

Interventions

BI 764532, dose 1 DRUG

BI 764532, dose 1

Also known as: Obrixtamig

Part 1: Dose group 1; Part 2: Expansion cohort; Part 3: Expansion cohort

BI 764532, dose 2 DRUG

BI 764532, dose 2

Also known as: Obrixtamig

Part 1: Dose group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• 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.
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.,
• 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.
• 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.
• Adequate organ function as defined in the protocol.
• 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).

You may not qualify if:

• 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.
• Presence of leptomeningeal disease or, part 2 and part 3: epidural disease including spinal cord compression.
• 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.
• 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.
• 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.
• Previous treatment with Delta-like ligand 3 (DLL3)-targeting T cell engagers or cell therapies.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (59)

Infirmary Cancer Care

Mobile, Alabama, 36607, United States

RECRUITING

Mayo Clinic-Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

COMPLETED

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

NOT YET RECRUITING

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

RECRUITING

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

COMPLETED

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

Virginia Commonwealth University Health- Adult Outpatient Pavilion

Richmond, Virginia, 23219, United States

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Multiprofile Hospital For Active Treatment-Uni Hospital Ltd.

Panagyurishte, 4500, Bulgaria

COMPLETED

MHAT Heart and brain

Pleven, 5800, Bulgaria

COMPLETED

West China Hospital, Sichuan University

Chengdu, 610041, China

RECRUITING

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

Hangzhou, 310016, China

RECRUITING

Qilu Hospital, Shangdong University

Jinan, 250012, China

RECRUITING

960 Hospital of the Chinese People's Liberation Army

Jinan, 250031, China

RECRUITING

The Second Affiliated Hospital to Nanchang University

Nanchang, 330006, China

RECRUITING

Shanghai Chest Hospital

Shanghai, 200030, China

RECRUITING

HOP Intercommunal

Créteil, 94000, France

COMPLETED

Hôpital Cochin

Paris, 75014, France

COMPLETED

HOP Civil

Strasbourg, 67091, France

COMPLETED

Evangelische Lungenklinik Berlin

Berlin, 13125, Germany

COMPLETED

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

RECRUITING

Asklepios Fachkliniken München-Gauting

Gauting, 82131, Germany

COMPLETED

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

ACTIVE NOT RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

RECRUITING

Aichi Cancer Center Hospital

Aichi, Nagoya, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

RECRUITING

Sendai Kousei Hospital

Miyagi, Sendai, 981-0914, Japan

COMPLETED

Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan

RECRUITING

Kindai University Hospital

Osaka, Sakai, 590-0197, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

RECRUITING

Japanese Foundation for Cancer Research

Tokyo, Koto-ku, 135-8550, Japan

RECRUITING

Hospital CUF Descobertas-Lisboa-69316

Lisbon, 1350-352, Portugal

RECRUITING

Hospital CUF Porto

Porto, 4100-180, Portugal

COMPLETED

Severance Hospital

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

COMPLETED

Samsung Medical Center

Seoul, 06351, South Korea

ACTIVE NOT RECRUITING

Hospital del Mar

Barcelona, 08003, Spain

COMPLETED

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

COMPLETED

NCKUH

Tainan, 704, Taiwan

COMPLETED

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

COMPLETED

Chang Gung Memorial Hospital, Linkou

Taoyuan, 333, Taiwan

COMPLETED

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

University College Hospital

London, WC1E 6AG, United Kingdom

RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Boehringer Ingelheim

CONTACT

1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The trial consists of 2 parts: Part 1: open label, randomized, with 2 treatment arms followed by: Part 2: open label, non-randomized, 1 treatment arm followed by: Part 3: open label, non-randomized, 1 treatment arm

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: May 31, 2023
• Study Start: October 13, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 24, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

DE (6); FR (3); PT (2); TW (3); JP (7); GB (4); KR (3); US (16); ES (5); BE (2); CN (6); BU (2)