1. Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.
- Author
-
Ravandi, Farhad, Subklewe, Marion, Walter, Roland B., Vachhani, Pankit, Ossenkoppele, Gert, Buecklein, Veit, Döhner, Hartmut, Jongen-Lavrencic, Mojca, Baldus, Claudia D., Fransecky, Lars, Pardee, Timothy S., Kantarjian, Hagop, Yen, Priscilla K., Mukundan, Lata, Panwar, Bharat, Yago, Marc R., Agarwal, Suresh, Khaldoyanidi, Sophia K., and Stein, Anthony
- Subjects
CYTOKINE release syndrome ,ACUTE myeloid leukemia ,ADVERSE health care events ,CANCER remission ,CYTOTOXINS - Abstract
AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell–mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day–1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF