COMy 2021 | AMG 420 and AMG 701 in R/R myeloma
Hermann Einsele, MD, FRCP, University of Würzburg, Würzburg, Germany, discusses the use of the bispecific T-cell engagers (BiTEs), AMG 420 and AMG 701, for the treatment of multiple myeloma. AMG 420, an anti-BCMA BiTE, was found to produce high rates of deep responses in clinical trials. Its requirement for continuous infusion led to focuses on developing alternative molecules with longer half-lives. AMG 701, a BCMA-directed half-life extended BiTE, was recently evaluated in a first-in-human Phase I trial (NCT03287908) in relapsed/refractory (R/R) myeloma. High response rates were observed, with some ongoing responses beyond 2 years. AMG 701 can be administered weekly, a benefit over AMG 420. This interview took place during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021.
Transcript (edited for clarity)
So AMG 420 was the first bispecific antibody that was used for the treatment of patients with multiple myeloma, and in this first-in-human trial, patients were allowed to receive five, or if they responded and tolerated the drug well, up to 10 cycles of treatment with AMG 420. And at the highest dose level, which was 400 micrograms per day, the overall response rate was 80% and 50% of patients achieved a stringent, complete remission, and were even MRD negative, and we had several patients with ongoing responses for more than one year...
So AMG 420 was the first bispecific antibody that was used for the treatment of patients with multiple myeloma, and in this first-in-human trial, patients were allowed to receive five, or if they responded and tolerated the drug well, up to 10 cycles of treatment with AMG 420. And at the highest dose level, which was 400 micrograms per day, the overall response rate was 80% and 50% of patients achieved a stringent, complete remission, and were even MRD negative, and we had several patients with ongoing responses for more than one year.
Now, AMG 420 is a typical BiTE molecule so it has to be given as a continuous infusion, which is difficult, especially for outpatient management of the patient. So the sponsor of the trial decided not to further develop AMG 420, but to switch to a molecule with a longer half-life, AMG 701. And in this trial, which was presented at the last ASH meeting, also patients that were heavily pre-treated were included, and again, with a very low toxicity, a very low grade 3 CRS in these patients, achieved a very good overall response rate of more than 80%. So again, a very nice treatment result, and we have ongoing responses in patients beyond even two years. And the beauty of the AMG 701 when compared with AMG 420 is that the drug can be given as a weekly IV application, and the AMG 420 had to be given as a continuous infusion.
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