Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.806243
Keywords
AML; acute myeloid leukaemia; CD123 expression; venetoclax (BCL2 inhibitor); bispecific antibody (bsAb); myelodysplastic and myeloproliferative syndromes
Categories
Funding
- Aptevo Therapeutics
- Greenville Health System, Institute for Translational Oncology Research, Greenville, South Carolina, United States [29605]
- University of Kansas Clinical Research Center [66205]
- Sylvester Comprehensive Cancer Center, University of Miami,Miami, Florida, United States
- University of Utah,Huntsman Cancer Institute, Salt Lake City, Utah, United States
- Ohio State University Wexner Medical Center/James Cancer Hospital
- Columbus, Ohio, United States
- Roswell Park Cancer Institute
- Buffalo, New York, UnitedStates
- Fred Hutchinson Cancer Research Center
- Seattle, Washington, United States
- University ofTexas Southwestern Medical Center, Dallas, Texas, UnitedStates
- University of Florida College of Medicine,Gainesville, Florida, United States
- University ofCalifornia, San Francisco Medical Center, San Francisco,California, United States
- [33136]
- [84112]
- [43210]
- [14263]
- [98109]
- [75390]
- [32610]
- [94143]
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APVO436 is a recombinant bispecific antibody that could be used to treat hematologic malignancies, particularly relapsed or refractory AML/MDS patients. Preliminary clinical trial results showed promising tolerability and activity of APVO436 in these patients, with activation of T cells.
APVO436 is a recombinant bispecific antibody designed to direct host cytotoxic T-cells to CD123-expressing blast cells in patients with hematologic malignancies. APVO436 showed promising tolerability and single-agent activity in relapsed or refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The primary purpose of this post-hoc analysis was to evaluate the therapeutic and pharmacodynamic effects of APVO436 in 14 R/R AML/MDS patients who had failed treatment with hypomethylating agents (HMA) or venetoclax plus HMA prior to being enrolled in the APVO436 Phase 1 dose-escalation study that was recently completed. Eight of these 14 patients had R/R AML and had failed treatment with HMA (N=2) or venetoclax plus HMA (N=6). The remaining 6 patients had R/R MDS and had also failed treatment with HMA (N=5) or venetoclax plus HMA (N=1). They were treated with APVO436 at submicrogram dose levels >0.08 mcg/kg that were active in preclinical NOD/SCID mouse xenograft models of AML. APVO436 activated patients' T-cells as evidenced by reduced numbers of circulating CD123(+)CD34(+) and CD33(+)CD34(+) peripheral blasts. Single-agent activity was observed at dose levels ranging from 0.1 mcg/kg to 0.7 mcg/kg in 4 R/R AML patients (50%), including 3 patients with prolonged stable disease (SD) and one patient with complete remission (CR). Likewise, 3 MDS patients had SD (50%) and 3 additional MDS patients (50%) had a marrow CR at dose levels ranging from 0.1 mcg/kg to 0.8 mcg/kg. The median survival for the combined group of 14 R/R AML/MDS patients was 282 days. This early evidence of single-agent activity of APVO436 in R/R AML/MDS patients who failed HMA with or without venetoclax provides proof of concept supporting its in vivo immunomodulatory and anti-leukemic activity and warrants further investigation of its clinical impact potential.
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