AMG 728

AMG 728 is a PD-L1-targeted 4-1BB bispecific molecule designed to enhance T-cell anti-tumor activity and persistence. Developed by Amgen, it simultaneously blocks PD-1/PD-L1 inhibitory signaling and activates 4-1BB costimulatory signaling in a PD-L1-dependent manner. This dual mechanism is intended to enhance T-cell activation and survival while minimizing the risk of systemic immune activation and off-tumor toxicity associated with non-targeted 4-1BB agonism. Preclinical studies have demonstrated that AMG 728 can improve the efficacy of T-cell engagers like tarlatamab (a DLL3-targeted bispecific) by promoting cytolytic effector differentiation and expanding memory T-cell populations, particularly in models of small cell lung cancer (SCLC).