by Dr. C.H. Weaver M.D. updated 6/2019
The BiTE® antibody construct represent an innovative immunotherapy approach that helps the body’s immune system target cancer cells. AMG 420 is a BiTE antibody construct drug that acts as a bridge for two proteins, BCMA and CD3 which can induce an immune response in patients with multiple myeloma.(1)
Clinical trial results released at the June 2019 American Society of Clinical Oncology (ASCO) meeting in Chicago in refractory patients look very promising.
Blinatumomab was the first investigational BiTE® antibody construct developed and was approved for the treatment of Acute Lymphoblastic Leukemia in 2015.(2) BiTE stands for "bi-specific T-cell engager" technology. This is a type of immunotherapy treatment that induces responses from T-Cells in the patient's own immune system. It does not target the cancer itself, instead AMG 420 consists of two particular proteins, BCMA and CD3, respectively. The BCMA portion binds to an antigen on the surface of a myeloma cell, and the CD3 binds to the surface of a T-cell. This bridge forms the way in which Cytotoxic T-Lymphocytes (CTLs) attack the myeloma cells causing cell death. CTLs are white blood cells that enter in and break down the cancer cell through lysis. Lysis means that the cell is broken down, which kills the cancer.
Nearly a third of patients with refractory multiple myeloma responded to treatment in this first-in-human, dose-escalation clinical trial. Overall 70% of treated individuals responded to the maximum tolerated dose (400 µg/day) evaluated in the study.(3)
The trial results released at ASCO included 42 patients who had received a median of four previous therapies and typically had a high tumor burden, reaching up to 80% of bone marrow in some.
Thirteen of 42 patients responded to AMG 420 therapy, including six complete responses, two very good partial responses and two partial responses; 11 of these patients responded in the first treatment cycle.
Seven of 10 patients treated with the AMG 420 dose of 400 µg/day responded to treatment: the 400 µg/day was the maximum tolerated dose, and it is the recommended dose that will be used in future trials.
An issue with CAR T cells for myeloma is that it takes a long time to construct the cells, and it’s very, very expensive. AMG 420 may be a shortcut or alternative to the same type of benefit seen with CAR T-cell therapy, except using an off-the-shelf product.
Researchers have also demonstrated that AMG 420 can be combined with CAR T-cells in patients with relapsed or refractory multiple myeloma. (4)
- The Lancet Haematology (2019 Aug 1. Epub ahead of print).