DAREON™-9: A Study to Test How Well Different Doses of BI 764532 Are Tolerated by People With Small Cell Lung Cancer When Taken Together With a Single Agent Chemotherapy

DAREON™-9: A Phase Ib Open-label Dose Escalation and Dose Confirmation Safety Study of Intravenous BI 764532 in Combination With a Single Agent Chemotherapy for the Treatment of Patients With Relapsed/Refractory Small Cell Lung Cancer After Platinum-based Chemotherapy

This study is open to adults with extensive stage small cell lung cancer. The study is in people with advanced cancer that had previously received platinum-based chemotherapy and are eligible to receive a single agent chemotherapy treatment.

The purpose of this study is to find the highest dose of BI 764532 that people can tolerate when taken together with a single agent chemotherapy. BI 764532 is an antibody-like molecule that may help the immune system fight cancer.

Participants may continue to take BI 764532 as long as they benefit from treatment and can tolerate it. During this time, participants visit the study site regularly. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Carcinoma (SCLC)
• Intervention / Treatment: Drug: BI 764532; Drug: Topotecan; Drug: Single agent chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75005
    • INS Curie
  • Strasbourg, France, 67091
    • HOP Civil
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Heidelberg, Germany, 69126
    • Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Würzburg, Germany, 97078
    • Universitätsklinikum Würzburg AÖR
• Poland
  • Lodz, Poland, 93-338
    • Polish Mother's Memorial Hospital - Research Institute
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
3. Histologically or cytologically confirmed small cell lung cancer (SCLC). Patients with tumours with mixed histology are eligible only if SCLC component is predominant and represent at least 50% of the overall tumour tissue.
4. Extensive stage - small cell lung cancer (ES-SCLC) that progressed or recurred following platinum-based treatment, and anti- programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) as applicable.
5. Patients must be eligible for single agent chemotherapy treatment (used in the trial) according to label.
6. Availability of archival tumour tissue sample.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Further inclusion criteria apply.

Exclusion Criteria:

1. Previous treatment in this trial.
2. Current enrolment in another investigational device or drug trial, or <30 days since ending another investigational device or drug trial(s).

3. Untreated or symptomatic brain metastases. Participants with treated, stable brain metastases are eligible provided they meet the following criteria:

   • Radiotherapy or major surgery for brain metastases was completed at least 2 weeks (for radiotherapy) or 4 weeks (for major brain metastases surgery) 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.
4. Presence of leptomeningeal carcinomatosis.
5. Prior participation in clinical trials of BI 764532, including receiving standard of care in these trials OR prior treatment with T cell engager (TcE) or cell therapies targeting delta-like ligand 3 (DLL3).
6. Persistent toxicity from previous treatments that has not resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, asthenia/fatigue, CTCAE Grade 2 neuropathy, or Grade 2 endocrinopathies controlled by replacement therapy).
7. 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.

8. Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except

   1. effectively treated non-melanoma skin cancers
   2. effectively treated carcinoma in situ of the cervix
   3. effectively treated ductal carcinoma in situ
   4. other effectively treated malignancy that is considered cured by local treatment Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B: BI 764532 + topotecan	Drug: BI 764532; BI 764532; Other Names: Obrixtamig; Drug: Topotecan; Topotecan
Experimental: Part A: BI 764532 low dose + topotecan/single agent chemotherapy	Drug: BI 764532; BI 764532; Other Names: Obrixtamig; Drug: Topotecan; Topotecan; Drug: Single agent chemotherapy; single agent chemotherapy
Experimental: Part A: BI 764532 medium dose + topotecan/single agent chemotherapy	Drug: BI 764532; BI 764532; Other Names: Obrixtamig; Drug: Topotecan; Topotecan; Drug: Single agent chemotherapy; single agent chemotherapy
Experimental: Part A: BI 764532 high dose + topotecan/single agent chemotherapy	Drug: BI 764532; BI 764532; Other Names: Obrixtamig; Drug: Topotecan; Topotecan; Drug: Single agent chemotherapy; single agent chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Occurrence of dose limiting toxicities (DLTs) in the maximum tolerated dose (MTD) evaluation period	up to 9 weeks
Part B: Occurrence of DLTs during the on-treatment period	up to 36 months
Part B: Occurrence of AEs during the on-treatment period	up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Occurrence of DLTs during the on-treatment period	up to 36 months
Part A: Occurrence of AEs during the on-treatment period	up to 36 months
Part B: Objective response	up to 36 months
Part B: Duration of response	up to 36 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Heterocyclic Compounds; Camptothecin; Alkaloids; Topotecan
• Other Study ID Numbers: 1438-0009; 2023-506007-26-00 (Ctis: CTIS (EU)); U1111-1293-4098 (Registry Identifier: WHO International Clinical Trials Registry Platform (ICTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No