How AMG 420 works
Multiple myeloma is a cancer that originates in plasma cells, a type of white blood cell. It can impact much of the body but especially target the bone marrow where plasma cells are made. Multiple myeloma cells produce a protein called B-cell maturation antigen (BCMA) in excess.
The immune system usually can recognize abnormal cells, such as cancer cells, and direct specific immune cells, such as T-cells, to destroy them. However, some tumor cells develop mechanisms to evade detection by the immune system.
AMG 420 is an immunotherapy, meaning that it does not directly target the tumor but aims to direct the body’s own immune system to attack cells producing a certain protein. It is made using Amgen’s proprietary BiTE or “bispecific T-cell engager” technology. AMG 420 consists of two proteins fused together, each designed to interact with a specific target — in this case, BCMA and CD3, a protein found on the surface of T-cells.
By binding simultaneously to BCMA on the tumor cell and CD3 on T-cells, AMG 420 forms a bridge between the T-cell and the tumor cell. This allows the T-cell to be able to recognize and target the tumor cell, with the intent of halting cancer progression and reducing tumor size.
Preclinical studies, carried out in mouse and monkey models of multiple myeloma, demonstrated that AMG 420 is capable of triggering a targeted immune response that is able to reduce the numbers of BCMA-positive tumor cells. Results of this work were published in the scientific journal, Leukemia.
AMG 420 in clinical trials
Boehringer initiated a Phase 1 dose escalation trial (NCT02514239) to determine the maximum tolerated dose of AMG 420. The open-label trial is currently enrolling an estimated 50 patients with advanced (relapsed and/or refractory) multiple myeloma at five sites in France and Germany.
The trial aims to assess the safety, tolerability, and — as a secondary measure — the anti-tumor activity of AMG 420. Patients’ response to AMG 420 will be monitored over a 21-month period, with a goal of determining an effective and tolerable dose for future trials.
AMG 420 is administered via injection into a vein.
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