Clinical trial NCT05882058: DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Neuroendocrine Neoplasms
Extra-pulmonary Neuroendocrine Carcinoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2023-05-31
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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 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 2 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, all participants receive the same dose of BI 764532. Part 2 is 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: 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: 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: 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

Exclusion criteria:

1. 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.
2. Presence of leptomeningeal disease or, part 2: epidural disease including spinal cord compression.
3. 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.
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 as per protocol. Further exclusion criteria apply.

Primary outcomes:
measure: Part 1: Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR)
timeFrame: up to 26 months
measure: Part 1: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period
timeFrame: up to 26 months
measure: Part 2: Objective response (OR)
timeFrame: up to 27 months
Secondary outcomes:
measure: Part 1: Duration of objective response (DOR) based on investigator assessment
timeFrame: up to 26 months
measure: Part 1: Progression-free survival (PFS) based on investigator assessment
timeFrame: up to 26 months
measure: Part 1: Disease control (DC), defined as best overall response of CR or PR or stable disease (SD) based on investigator assessment
timeFrame: up to 26 months
measure: Part 1: Overall survival (OS), defined as the time from treatment start until death from any cause
timeFrame: up to 26 months
measure: Part 1: Change from baseline in EORTC QLQ-C30 physical functioning domain score
timeFrame: at baseline, at month 26
measure: Part 1: Change from baseline in EORTC QLQ-C30 role functioning domain score
timeFrame: at baseline, at month 26
measure: Part 1: Occurrence of treatment-emergent AEs leading to study drug discontinuation during the on-treatment period
timeFrame: up to 26 months
measure: Part 2: Duration of objective response (DOR) based on blinded independent central review
timeFrame: up to 27 months
measure: Part 2: Progression-free survival (PFS) based on blinded independent central review
timeFrame: up to 27 months
measure: Part 2: Disease control (DC) based on blinded independent central review
timeFrame: up to 27 months
measure: Part 2: Overall survival (OS), defined as the time from treatment start until death from any cause
timeFrame: up to 27 months
measure: Part 2: Change from baseline in EORTC QLQ-C30 physical functioning domain score
timeFrame: up to 27 months
measure: Part 2: Change from baseline in EORTC QLQ-C30 role functioning domain score
timeFrame: up to 27 months
measure: Part 2: Occurrence of treatment-emergent AEs leading to study drug discontinuation during the on-treatment period
timeFrame: up to 27 months
measure: Part 2: Occurrence of treatment-emergent adverse events (TEAEs) during the on-treatment period
timeFrame: up to 27 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Infirmary Cancer Care
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic-Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Richmond
country: United States
facility: Virginia Commonwealth University Health- Adult Outpatient Pavilion
state: Virginia
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Panagyurishte
country: Bulgaria
facility: MHAT UniHospital
city: Pleven
country: Bulgaria
facility: MHAT Heart and brain
city: Chengdu
country: China
facility: West China Hospital
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
city: Jinan
country: China
facility: Qilu Hospital, Shangdong University
city: Jinan
country: China
facility: 960 Hospital of the Chinese People's Liberation Army
city: Nanchang
country: China
facility: The Second Affiliated Hospital to Nanchang University
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Créteil
country: France
facility: HOP Intercommunal
city: Paris
country: France
facility: HOP Cochin
city: Strasbourg
country: France
facility: HOP Civil
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
city: Großhansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Miyagi, Sendai
country: Japan
facility: Sendai Kousei Hospital
city: Osaka, OsakaSayama
country: Japan
facility: Kindai University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas-Lisboa-69316
city: Porto
country: Portugal
facility: Hospital CUF Porto
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital(Linkou)
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: The Christie
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
References: