TEST:

VENTANA DLL3 (SP347) Assay

There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.

The SLR findings indicate that most studies assessing DLL3 in SCLC have relied on IHC methodology. Despite the range of thresholds used for evaluating positivity, DLL3 is notably expressed in SCLC. The frequency and impact of aberrant DLL3 localization was not addressed in these studies and minimal data on comparison of IHC with other methodologies exists.

Because of its high expression in neuroendocrine tumors compared to normal tissue, delta-like ligand 3 (DLL3) has emerged as a new therapeutic target in this setting.1,2 Targeting DLL3 with the half-life extended bispecific T cell engager (HLE BiTE®) immune therapy, tarlatamab, in a phase 1 clinical trial has demonstrated promising anti-tumor activity in small cell lung cancer (SCLC) patients.3 In order to more precisely guide patient selection and clinical trial design, a better understanding and quantification of DLL3 expression is required...Our work confirms that most high-grade neuroendocrine tumors express DLL3 across histology types and TNM stage. Our results suggest that a large subset of patients with high-grade lung neuroendocrine tumors may be a target population of interest for DLL3-targeted therapies.

"Immunoreactivity was also observed in other neoplastic and nonneoplastic tissues. Our study findings provided the profile of DLL3 staining characteristics that can be used for determining the level of DLL3 expression in small cell lung cancer."