Clinical Trials List
Protocol Number1438-0005
NCT Number(ClinicalTrials.gov Identfier)NCT05882058
Completed
2023-11-01 - 2025-12-31
Phase II
Terminated3
ICD-10C33
Malignant neoplasm of trachea
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.0
Malignant neoplasm of trachea
DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas
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Trial Applicant
Boehringer Ingelheim
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yuh-Min Chen Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- Chia-I Shen Division of Thoracic Medicine
- YEN-HAN TSENG Division of Thoracic Medicine
- Yung-Hung Luo 無
- Ming-Huang Chen Division of Hematology & Oncology
- 蕭慈慧 無
- Yi-Ping Hung Division of Hematology & Oncology
- Hsu-ching Huang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 吳教恩 Division of Hematology & Oncology
- 柯皓文 Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- 林定佑 Division of Hematology & Oncology
- 張境夫 Division of Hematology & Oncology
- Cheng-Ta Yang 無
- 枋岳甫 Division of Thoracic Medicine
- Ping-Chih Hsu Division of Hematology & Oncology
- 黃宗楨 無
- Chih-Liang Wang Division of Hematology & Oncology
- 邱立忠 Division of Thoracic Medicine
- Chien-Ying Liu 無
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
Chien-Chung Lin
Co-Principal Investigator
- Chian-Wei Chen Division of General Internal Medicine
- Chun-Hui Lee Division of Hematology & Oncology
- 蔡政軒 Division of General Internal Medicine
- Shang-Yin Wu 無
- Seu-Chun Yang Division of General Internal Medicine
- 郭鈞偉 Division of General Internal Medicine
- Wu-Chou Su
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Small Cell Lung Carcinoma、 Neuroendocrine Neoplasms 、Extra-pulmonary Neuroendocrine Carcinoma
Objectives
The primary objective of this trial is to evaluate the safety and efficacy of two dose levels of BI 764532 monotherapy in patients with SCLC who have progressed or relapsed after at least two lines of prior therapy, including at least one platinum-based regimen, and in patients with histologically or cytologically confirmed advanced or metastatic epNEC (excluding MCC, MTC, and NEPC) or pulmonary LCNEC (as defined by the 2022 World Health Organization classification of neuroendocrine tumors) who have progressed or relapsed after receiving at least one platinum-based regimen.
Secondary objectives are to further evaluate the efficacy of BI 764532 monotherapy; to explore the impact of BI 764532 on core patient-reported outcomes (PROs); and to further evaluate the safety and tolerability of BI 764532 monotherapy.
Test Drug
N/A
Active Ingredient
BI 764532
Dosage Form
N/A
Dosage
10mg/vial
Endpoints
The primary endpoints of the trial are:
• Objective response (OR), defined as the best overall response of a complete response (CR) or a confirmed partial response (PR) as assessed by the trial administrator according to RECIST version 1.1 from the date of treatment initiation until the earliest date of disease progression, death, or at the last evaluable tumor assessment before the initiation of subsequent anticancer therapy, at loss of follow-up, or at the time of withdrawal of consent.
• Treatment-adverse events (TEAEs).
• Objective response (OR), defined as the best overall response of a complete response (CR) or a confirmed partial response (PR) as assessed by the trial administrator according to RECIST version 1.1 from the date of treatment initiation until the earliest date of disease progression, death, or at the last evaluable tumor assessment before the initiation of subsequent anticancer therapy, at loss of follow-up, or at the time of withdrawal of consent.
• Treatment-adverse events (TEAEs).
Inclution Criteria
Inclusion criteria:
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: 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: 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).
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
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: 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: 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).
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
Exclusion Criteria
Exclusion criteria:
Untreated or symptomatic brain metastases. (Part 2: with 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: epidural disease including spinal cord compression.
Part 1: Active/previous history of interstitial lung disease or non-infectious pneumonitis (any grade).
Part 2: 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.
Unresolved toxicity from prior anti-tumour therapy, defined as per protocol. Further exclusion criteria apply.
Untreated or symptomatic brain metastases. (Part 2: with 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: epidural disease including spinal cord compression.
Part 1: Active/previous history of interstitial lung disease or non-infectious pneumonitis (any grade).
Part 2: 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.
Unresolved toxicity from prior anti-tumour therapy, defined as per protocol. Further exclusion criteria apply.
The Estimated Number of Participants
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Taiwan
12 participants
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Global
120 participants
