Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.
Farhad RavandiMarion SubkleweRoland Bruno WalterPankit VachhaniGert OssenkoppeleVeit BueckleinHartmut DöhnerMojca Jongen-LavrencicClaudia D BaldusLars FranseckyTimothy S PardeeHagop M KantarjianPriscilla K YenLata MukundanBharat PanwarMarc R YagoSuresh AgarwalSophia K KhaldoyanidiAnthony SteinPublished in: Leukemia & lymphoma (2024)
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.
Keyphrases
- acute myeloid leukemia
- open label
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- end stage renal disease
- ejection fraction
- acute lymphoblastic leukemia
- clinical trial
- newly diagnosed
- endothelial cells
- prognostic factors
- mesenchymal stem cells
- rheumatoid arthritis
- multiple myeloma
- diffuse large b cell lymphoma
- squamous cell carcinoma
- randomized controlled trial
- systemic lupus erythematosus
- oxidative stress
- signaling pathway
- cancer therapy
- high dose
- study protocol
- phase ii
- drug induced
- locally advanced