Tarlatamab

Tarlatamab (AMG-757) is a bispecific T-cell engager (BiTE) antibody targeting delta-like ligand 3 (DLL3). DLL3 is a target that is selectively expressed in small-cell lung cancer (SCLC) tumors, but with minimal normal tissue expression. Tarlatamab has the KDs of 0.64 nM and 0.50 nM for human and nonhuman primate (NHP) DLL3, respectively. Tarlatamab has the KDs of 14.9 nM and 12 nM for human and NHP CD3, respectively. Tarlatamab is a first-in-class HLE BiTE immuno-oncology therapy targeting DLL3 and has the potential for SCLC research.

Tarlatamab (AMG-757; 0-10 nM; 48 hours) has potent, specific cytotoxic activity against DLL3-expressing SCLC cell lines in vitro^[1].
Tarlatamab (0-10 nM; 4-72 h) increased granzyme B levels and cytotoxicity over time, with maximal signal observed at 48 hours. Markers of T-cell activation or inflammation, CD69, CD71, PD-1, and PD-L1 (37-39) were upregulated^[1].

Tarlatamab (AMG-757; 3 mg/kg; IP; once weekly for 3 weeks) drives tumor regression in mouse models of SCLC^[1].
Tarlatamab (IP; 12 μg/kg; single dose) has a mean half-life of 234 hours (9.8 days), a mean clearance of 0.487 mL/hour/kg and a steady-state volume of distribution of 146 mL/kg in nonhuman primates (NHPs)^[1].

References:
[1]. Michael J Giffin, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res. 2021 Mar 1;27(5):1526-1537.