2. Academic Validation
  3. Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study

Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study

  • Leuk Lymphoma. 2024 Sep;65(9):1281-1291. doi: 10.1080/10428194.2024.2346755.
Farhad Ravandi 1,  Marion Subklewe 2 3,  Roland B Walter 4,  Pankit Vachhani 5,  Gert Ossenkoppele 6,  Veit Buecklein 2 3,  Hartmut Döhner 7,  Mojca Jongen-Lavrencic 8,  Claudia D Baldus 9,  Lars Fransecky 9,  Timothy S Pardee 10,  Hagop Kantarjian 1,  Priscilla K Yen 11,  Lata Mukundan 12,  Bharat Panwar 12,  Marc R Yago 12,  Suresh Agarwal 11,  Sophia K Khaldoyanidi 11,  Anthony Stein 13
Affiliations

Affiliations

  • 1 Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
  • 2 Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
  • 3 Laboratory for Translational Research, Gene Center, LMU Munich, Munich, Germany.
  • 4 Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • 5 Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 6 Amsterdam University Medical Center, Amsterdam, The Netherlands.
  • 7 Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
  • 8 Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands.
  • 9 Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany.
  • 10 Department of Internal Medicine, Section on Hematology and Oncology, Atrium Health Wake Forest Baptist, Winston-Salem, NC, USA.
  • 11 Amgen Inc, Thousand Oaks, CA, USA.
  • 12 Amgen Inc, South San Francisco, CA, USA.
  • 13 Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA, USA.
PMID: 38712673 DOI: 10.1080/10428194.2024.2346755
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.

Keywords

AML; BiTE®; CD33; CRS; T-cell; dose-escalation; interleukin.

Figures
Products