Analysis of delta-like ligand 3 (DLL3) expression levels and characteristics of patients (pts) with advanced extrapulmonary neuroendocrine carcinomas (epNECs) from an ongoing phase I trial.

2642 Background: Specific DLL3 expression on the surface of epNEC tumor cells makes it a promising therapeutic target, but there is a lack of prospective data on DLL3 expression patterns in pts with epNEC. Obrixtamig (BI 764532) is a DLL3/CD3 IgG-like T-cell engager. The first-in-human phase I trial (NCT04429087) showed obrixtamig activity in pts with DLL3-positive epNEC, especially pts with DLL3-high tumors (Capdevila et al, ASCO 2025, #3004). We report updated DLL3 expression data and pt/tumor characteristics in pts with epNEC from NCT04429087. Methods: DLL3 IHC was performed with an investigational DLL3 antibody (SP347) at the Roche CDx CAP/CLIA Laboratory. DLL3 expression was categorized as: negative (absent or weak tumor cell TC membrane/cytoplasm staining), positive (moderate-to-strong staining in any TCs), high (≥50% moderate-to-strong TC staining), or low (ULN, n (%) 22 (43.1) / 29 (56.9) 16 (38.1) / 26 (61.9) Prior lines of therapy: 1 / 2 / 3 / >3 12 (23.5) / 17 (33.3) / 9 (17.6) / 13 (25.5) 11 (26.2) / 12 (28.6) / 10 (23.8) / 9 (21.4) Median duration of prior anticancer treatment, weeks (range) 22 (5–349) 22 (8–148) Prior radiotherapy / surgery / anti PD-(L)1, n (%) 22 (43.1) / 28 (54.9) / 14 (27.5) 11 (26.2) / 24 (57.1) / 9 (21.4) Liver / brain metastases, n (%) 40 (78.4) / 7 (13.7) 30 (71.4) / 3 (7.1) Median sum of diameters of target lesions, mm (IQR) 87.5 (64.0–123.0) 117.3 (66.2–176.0)