995O - Interim Results from a Phase 1 First-in-Human study of flotetuzumab, a CD123 x CD3 bispecific DART molecule, in AML/MDS

Date 10 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Leukaemia
Haematologic Malignancies
Presenter Norbert Vey
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors N. Vey1, J. Davidson-Moncada2, G.L. Uy3, M. Foster4, D. Rizzieri5, J. Godwin6, M. Topp7, F. Ciceri8, M. Carrabba8, G. Martinelli9, G.A. Huls10, A. Wegener11, M. Shannon2, K. Tran12, J. Sun13, E. Bonvini14, B. Löwenberg15, J. Wigginton2, J.F. Dipersio3
  • 1Département D’hématologie, Institut Paoli-Calmettes, 13009 - Marseille/FR
  • 2Clinical Development, MacroGenics, Inc., 20850 - Rockville/US
  • 3Division Of Oncology, Washington University School of Medicine, 63110 - St. Louis/US
  • 4Division Of Hematology/oncology, UNC Lineberger Comprehensive Cancer Center, 27599 - Chapel Hill/US
  • 5Hematology/oncology, Duke University Medical Center, 27522 - Durham/US
  • 6Division Of Hematology/oncology, Providence Cancer Center, 97213 - Portland/US
  • 7Division Of Hematology/oncology, Universitätsklinikum Würzburg, 97080 - Wurzburg/DE
  • 8Department Of Hematology, University Vita-Salute San Raffaele, 20132 - Milano/IT
  • 9Department Of Hematology, Policlinico Sant'Orsola-Malpighi, 40138 - Bologna/IT
  • 10Department Of Hematology, University Medical Center Groningen, 9713GZ - Groningen/NL
  • 11Clinical Development, Servier, Paris/FR
  • 12Clinical Operations, MacroGenics, Inc., 20850 - Rockville/US
  • 13Biostatistics, MacroGenics, Inc., 20850 - Rockville/US
  • 14Research, MacroGenics, Inc., 20850 - Rockville/US
  • 15Department Of Hematology, Erasmus University Medical Center, 3000CA - Rotterdam/NL



Acute myeloid leukemia (AML) CD34+, CD38- cells highly express CD123, associated with high-risk disease and disease progression. CD123 expression on normal HSC is negligible, enabling a promising strategy of preferential ablation with a CD123-targeted approach. Flotetuzumab (MGD006/S80880), a novel CD123 x CD3 bispecific DART protein, is designed to target CD123+ cells for elimination by T cells.


The Ph 1 dose-escalation study will define the safety profile, maximum tolerated dose and schedule (MTDS), and preliminary anti-leukemic activity of flotetuzumab. Relapsed/refractory (R/R) AML or intermediate-2/high-risk MDS will be treated with 28 day cycles of continuous infusion at doses from 3 to 1000 ng/kg/day. During C1W1, patients receive a lead-in dose (LID) of 30 ng/kg/day for 3 days followed by 100 ng/kg/day for 4 days. During C1W2-4, patients receive the cohort target dose (300-1000ng/kg/day) on either a 4-day on/3-day off or a continuous 7-day on weekly schedule. At Cycle 2 and beyond, patients are treated on a 4-day on/3-day off schedule at the cohort target dose for a maximum of 12 cycles, 2 cycles after a CR, DLT or DP. Cohort expansion will enroll 24 AML and 24 MDS patients at the MTDS. Disease status is assessed by IWG criteria.


Patients with R/R AML/MDS (35/3) have been treated with flotetuzumab, up to a dose of 500ng/kg/day. Flotetuzumab has demonstrated acceptable tolerability to date, with no MTDS yet defined for either schedule. The most common drug-related adverse event was infusion-related reaction/cytokine-release syndrome (29/38, 76% any grade; 3/38, 8% G3). Drug-related adverse events ≥G3 were observed in 14/38 (36%) of patients overall. A LID strategy and early use of tocilizumab ameliorated this toxicity and limits corticosteroid use. At 500ng/kg/day, anti-leukemic activity has been observed in 4/8 patients treated, including CRi (n = 2), morphologic leukemia free state (n = 1) and bone marrow blast reduction >50% (n = 1).


To date flotetuzumab has an acceptable safety profile and demonstrated early evidence of anti-leukemic activity.

Clinical trial identification


Legal entity responsible for the study

MacroGenics, Inc.


MacroGenics, Inc. Servier


N. Vey: Amgen, Celgene, Bristol-Myers Squib, Novartis, Servier. J. Davidson-Moncada: MacroGenics, Inc. M. Foster: Celgene MacroGenics. D. Rizzieri: Novartis, Abbvie, Pfizer, Teva, Incyte, Celgene, Gilead, Seattle Genetic, Millenium (spouse). J. Godwin: Bristol-Myers Squib, AbbVie. M. Topp: Amgen, Roche, Regeneron. G. Martinelli: Novartis, Bristol-Myers Squib, Celgene - speaker bureau Ariad/Incyte, Pfizer, Roche, MSD, Celgene – consultant. A. Wegener: Servier. M. Shannon, K. Tran, J. Sun, E. Bonvini: MacroGenics. J. Wigginton: Employee of MacroGenics. Receive salary, stock/options. J.F. Dipersio: Magenta, Celegen, Bioline, Vasculox, Cellworks, Rivervest, Hemedicus, DAVA oncology, Bristol-Myers Squib, Asteria, Amphivena, Bluebird. All other authors have declared no conflicts of interest.