TEST:

VENTANA DLL3 (SP347) Assay

Both IHC and mRNA ISH showed significant correlation in tumors and lymph node metastasis. An observed trend suggested improved survival in patients with no DLL3 expression.

High-grade and low-grade MTC have different expression profiles. DLL3 should be explored as a predictor of aggressive disease and poor outcome in MTC.

"Tarlatamab, targeting DLL3 and CD3, showed a 40% response rate in previously treated patients... In 248 early-stage SCLC, positivity for DLL3 was 58% with IHC and 87% with mRNA ISH. A trend for improved survival in patients with no DLL3 expression was observed. Future studies on DLL3 might improve SCLC treatment SCLC."

Findings from this phase 1 study of tarlatamab in pts with NEPC demonstrated manageable safety with encouraging anti-tumor activity in DLL3 expressing NEPC. Further investigation is ongoing.

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."