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 K D s of 0.64 nM and 0.50 nM for human and nonhuman primate (NHP) DLL3, respectively. Tarlatamab has the K D s 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.In VitroTarlatamab (AMG-757; 0-10 nM; 48 hours) has potent, specific cytotoxic activity against DLL3-expressing SCLC cell lines in vitro. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: SCLC cell lines (DMS 79, NCI-H2171, NCI-H889, SHP-77, NCI-H211,COR-L279) Concentration: 0-10 nM Incubation Time: 48 hours Result: AMG 757 effectively engaged human T cells to kill SCLC cell lines, including those with very low DLL3 expression levels.In VivoTarlatamab (AMG-757; 3 mg/kg; IP; once weekly for 3 weeks) drives tumor regression in mouse models of SCLC . 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) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female NOD.Cg-PrkdcscidIl2rgtm1Sug/JicTac (NOG) mice with patient-derived SCLC tumor fragments (LXFS 1129 and LXFS 538) Dosage: 3 mg/kg Administration: IP; once weekly for 3 weeks Result: Led to 83% tumor regression and an overall significant reduction in tumor volume compared with that in mice which received a control HLE BiTE molecule in the LXFS 1129 model. Induced 98% tumor regression in the LXFS 538 model.Form:Liquid.