Pharmacokinetics and pharmacodynamics of Tarlatamab, DLL3-Targeted FDA-approved Bispecific T-Cell Engager

Small-cell lung cancer (SCLC) is a common aggressive cancer type, that exhibits overall lower rate of survival and poor prognosis. Treatment options of SCLC are limited including chemotherapy, radiotherapy, and surgery to dissect tumors. However, these therapies are not very effective in treating SCLCs, and no available therapies are in third-line or beyond. The notch signaling pathway plays a central role in regulating cell proliferation, survival, and maintenance. Notch signaling in SCLC is dysregulated and induces oncogenicity. DLL3 is a notch ligand whose expression is nominal in normal conditions and the DLL3 is overexpressed in SCLC which promotes tumor cell proliferation, migration, and invasiveness. Over 85% of human SCLC express elevated DLL3 on the cell surface. Therefore, targeting DLL3 is a promising therapeutic approach to treat SCLC. Bispecific T-cell engagers (BiTEs) molecule binds to DLL3 and CD3 simultaneously leading to T-cell activation and T-cell-induced tumor eradication. Tarlatamab is a half-life extended DLL3-targeted T-cell-engaging bispecific antibody (BsAb) that exhibited superior antitumor efficacy in the preclinical in vitro and in vivo model. Tarlatamab is the only DLL3-engaging BiTE molecule that was approved by the USFDA on May 16th, 2024 under the brand name Imdelltra (Amgen Inc). It showed higher clinical efficacy and the pharmacodynamic study reported that higher T-cell activation and IFN-γ elevation were mediated after the first dose of tarlatamab. Manageable safety profile with higher efficacy rate was reported in the clinical study. In this review, we present immune therapy, and pharmacokinetic and pharmacodynamic profiles of tarlatamab based on the clinical study reports.