A First-In-human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 764532 Administered by Parenteral Route in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
This study is open to adults with small cell lung cancer and other neuroendocrine cancers 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 and the best treatment schedule that people can tolerate. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. In this study, BI 764532 is given to people for the first time. That means no clinical data are available for BI 764532. Participants get BI 764532 either weekly or once every 3 weeks. 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 20 times depending on the response to the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.
• Signed and dated, written informed consent form (ICF2, ICF3 or ICF4) in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Locally advanced or metastatic cancer not amenable to curative treatment; of 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 DLL3 expression (on archived tissue or instudy fresh biopsy) according to central pathology review in order to start BI 764532
⁃ Patients with tumours 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 tumour tissue.
• For back-fill cohorts only: patient has agreed to and signed an IC to provide mandatory pre-treatment and on-treatment fresh tumor biopsy.
• Patient has failed or is not eligible for available standard therapies according to local guidelines. Standard therapies should include at least one line of chemotherapy that should include platinum for patients with small cells carcinoma tumors histologies.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• At least one evaluable lesion outside of CNS as defined per modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• Subjects with 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.
• Adequate liver, bone marrow and renal organ function Further inclusion criteria apply.