AMG 436

AMG 436 is a bispecific T-cell engager (BiTE) developed by Amgen for the treatment of microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) solid tumors. As a BiTE molecule, it is designed to bridge the immune system and cancerous cells by simultaneously binding to the CD3 epsilon subunit of the T-cell receptor complex and a specific tumor-associated antigen. In the context of MSI-H tumors, which are characterized by a high burden of mutations, the drug is intended to target a shared frameshift neoantigen resulting from the mismatch repair deficiency. This dual binding facilitates the formation of an immunological synapse, leading to T-cell activation and the subsequent directed lysis of the tumor cells. A Phase 1/1b clinical trial (NCT04469504) was initiated to evaluate its safety and pharmacokinetics as both a monotherapy and in combination with other anti-cancer therapies; however, the study was withdrawn by Amgen in 2020 before any participants were enrolled, and development for this indication appears to have been discontinued.