AMG0-420 is a new bi-specific antibody that is being tested in Phase I clinical trials. It is a small molecule that binds CD3 on T cells with a common target found on all myeloma cells called BCMA. By binding the two together, the T cell is forced to kill the myeloma cell.
While CAR T cell therapy is targeting the same BCMA proteins, this drug is an off-the-shelf approach to also use the immune system to combat myeloma.
Because it has a short half-life, it is given as a continuous infusion for four weeks on and two weeks off. Patients are first given the drug in the hospital so any potential side effects can be addressed (such as potential cytokine release syndrome). Then they are sent home with a pump. There are multiple courses of therapy and patients can live a relatively normal lifestyle while still getting the infusion.
Dr. Luciano Costa joined the Myeloma Crowd to share the recent study results from the ASCO 2019 conference.
The Phase I study objectives were to assess safety and activity. In this study, 6-week cycles of AMG-420 were given for less than 5 cycles or until disease progression.
Patients joining the study had received more than two lines of therapy including a proteasome inhibitor and an immunomodulatory drug.
As of December 2018, 42 patients had received AMG 420 in different doses. Side effects included infections and neuropathy. The 800 µg/d dose was determined to be too high. At a dose of 400 µg/d (ten patients) there was a 70% response rate:
- MRD negative stringent complete responses – 5 patients
- Very good partial response – 1 patient
- Partial response – 1 patient
Amgen and others are working on ways of making this infusion more convenient by adding a half-life extender (AMG-701). The BiTE is another helpful tool in the myeloma arsenal and is continuing through additional Phase I studies. To find the AMG-420 in open clinical trials, click here: