A Study to Test How Well Different Doses of BI 764532 in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3

Study Purpose

This study is open to adults with small cell lung cancer and other neuroendocrine tumours that are positive for the tumour marker Delta-like 3 (DLL3). 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 out the highest dose of BI 764532 that people can tolerate when taken together with another medicine called ezabenlimab. BI 764532 and ezabenlimab are antibodies that may help the immune system fight cancer. Participants get BI 764532 and ezabenlimab as infusions into a vein. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about every week. 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion criteria. 1. Age ≥18 years. 2. Signed and dated, written informed consent form (main ICF) in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses. 3. Diagnosed with locally advanced, metastatic or relapsed cancer not amenable to curative treatment of the following histologies:

- Small cell lung carcinoma (SCLC) - Large cells neuroendocrine lung carcinoma(LCNEC) - Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin.

- Tumours must be positive for Delta-like 3 (DLL3) expression (on archived tissue) according to central pathology review in order to start BI 764532 .

- Patients with tumors with mixed histologies for any above type are eligible only if neuroendocrine carcinoma/small tumor cells component is predominant and represent at least 50% of the overall tumor tissue.

4. Patient who failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted available treatment options known to prolong survival for their disease. Previous therapies should include at least one line of platinum-based chemotherapy. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6. At least one evaluable lesion outside of Central Nervous System (CNS) as defined per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 7. Subjects with brain metastases are eligible provided they meet the following criteria:

- radiotherapy or surgery for brain metastases was completed at least 2 weeks or 4 weeks respectively, 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 CNS disease.

8. Male or female patients. Women of childbearing potential (WOCBP)1 and men able to father a child must be ready and able to use highly effective 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.These methods must be used during the study and for at least 3 months after the last dose of BI 764532. A list of contraception methods meeting these criteria is provided in the patient information. Further inclusion criteria apply. Exclusion criteria. 1. Previous treatment with T-cell-engager (TcE) or cell therapies targeting DLL3. Other DLL3 targeting agents (like RovaT) are allowed only if DLL3 positivity is documented after completion of treatment with DLL3 targeting agent in post-treatment biopsy. 2. Previous or concomitant malignancies other than the one treated in this trial within the last 2 years except:

- effectively treated non-melanoma skin cancers.

- effectively treated carcinoma in situ of the cervix.

- effectively treated ductal carcinoma in situ.

- other effectively treated malignancy that is considered cured by local treatment.

3. Major injuries and/or surgery or bone fracture within 28 days of first dose BI 764532, or planned surgical procedures. 4. Known leptomeningeal disease or spinal cord compression due to metastatic disease. 5. Anticoagulant treatment that cannot be safely interrupted based on opinion of the investigator if medically needed. 6. Patients who have been febrile, have had leukocytosis, or any clinical signs of infection within 48 h prior to randomization/start of trial treatment are not eligible. Oral or intravenous antimicrobials for management of fungal, bacterial, viral, or other infection are prohibited within 7 days prior to randomization/start of trial treatment. The use of antimicrobials for routine infection prophylaxis is acceptable. 7. Severe acute respiratory syndrome coronavirus 2 (SARS COV2) infection within 2 weeks prior to study entry (confirmed via Polymerase chain reaction (PCR) test or other applicable test as per local requirements) or suspected SARS-CoV-2 infection as per physician assessment, or close contact (within 1 week) with an individual with confirmed SARS-CoV-2 infection. 8. Any of the following known laboratory evidence of hepatitis virus infection:

- Positive results of hepatitis B surface (HBs) antigen.

- Presence of hepatitis B core (HBc) antibody together with hepatitis B virus (HBV)-Deoxyribonucleic Acid (DNA) - Presence of hepatitis C Ribonucleic acid (RNA) Further exclusion criteria apply.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05879978
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Boehringer Ingelheim
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Belgium, France, Germany, Japan
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Small Cell Lung Carcinoma (SCLC), Neuroendocrine Neoplasms
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: BI 764532 + ezabenlimab treatment group

Successive cohorts of patients will receive increasing doses of BI 764532 in combination with ezabenlimab until the maximum tolerated dose (MTD) is reached, or upon decision of Dose Escalation Committee (DEC).

Interventions

Drug: - BI 764532

BI 764532

Drug: - Ezabenlimab

Ezabenlimab

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.