Phase I trial of the DLL3/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas

Future Oncol. 2022 Aug;18(24):2639-2649. doi: 10.2217/fon-2022-0196. Epub 2022 Jul 11.


Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 monotherapy.

Trial registration: NCT04429087.

Keywords: BI 764532; DLL3; T-cell engager; neuroendocrine carcinoma; small-cell lung cancer.

Plain language summary

DLL3 is a protein involved in development of the embryo during pregnancy. It has also been found on the surface of cells involved in the development of certain types of lung cancer and other tumors. The T-cell engager BI 764532 binds to DLL3 and cells of the immune system simultaneously, resulting in the death of tumor cells. Here we describe the rationale for, and design of, a clinical study of BI 764532 in patients with small-cell lung cancer and other tumors containing DLL3. The aim of the study is to find the highest acceptable dose of BI 764532 that can be tolerated by patients, and explore the safety and efficacy of BI 764532. Clinical Trial Registration: NCT04429087 (

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific* / therapeutic use
  • Carcinoma, Neuroendocrine* / drug therapy
  • Carcinoma, Neuroendocrine* / genetics
  • Carcinoma, Neuroendocrine* / pathology
  • Clinical Trials, Phase I as Topic
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Membrane Proteins / genetics
  • Mice
  • Multicenter Studies as Topic
  • Neoplasm Recurrence, Local / pathology
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / genetics
  • T-Lymphocytes


  • Antibodies, Bispecific
  • DLL3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins

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