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
  • 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.
Products