PMID- 34439266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230920
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 16
DP  - 2021 Aug 15
TI  - A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in 
      Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic 
      Syndrome.
LID - 10.3390/cancers13164113 [doi]
LID - 4113
AB  - APVO436 is a recombinant T cell-engaging humanized bispecific antibody designed 
      to redirect host T cell cytotoxicity in an MHC-independent manner to 
      CD123-expressing blast cells from patients with hematologic malignancies and has 
      exhibited single-agent anti-leukemia activity in murine xenograft models of acute 
      myeloid leukemia (AML). In this first-in-human (FIH) multicenter phase 1B study, 
      we sought to determine the safety and tolerability of APVO436 in R/R 
      AML/myelodysplastic syndrome (MDS) patients and identify a clinically active 
      recommended phase 2 dose (RP2D) level for its further clinical development. A 
      total of 46 R/R AML/MDS patients who had failed 1-8 prior lines of therapy 
      received APVO436 as weekly intravenous (IV) infusions at 10 different dose 
      levels, ranging from a Minimum Anticipated Biological Effect Level (MABEL) of 0.3 
      mcg to 60 mcg. APVO436 exhibited a favorable safety profile with acceptable 
      tolerability and manageable drug-related adverse events (AEs), and its maximum 
      tolerated dose (MTD) was not reached at a weekly dose of 60 mcg. The most common 
      APVO436-related AEs were infusion-related reactions (IRR) occurring in 13 (28.3%) 
      patients and cytokine release syndrome (CRS) occurring in 10 (21.7%). The single 
      dose RP2D level was identified as 0.2 mcg/kg. Preliminary efficacy signals were 
      observed in both AML and MDS patients: Prolonged stable disease (SD), partial 
      remissions (PR), and complete remissions (CR) were observed in R/R AML patients 
      as best overall responses to APVO436 at the RP2D level. Three of six evaluable 
      MDS patients had marrow CRs. The safety and preliminary evidence of efficacy of 
      APVO436 in R/R AML and MDS patients warrant further investigation of its clinical 
      impact potential.
FAU - Uckun, Fatih M
AU  - Uckun FM
AUID- ORCID: 0000-0001-9334-183X
AD  - Aptevo Therapeutics, Seattle, WA 98121, USA.
AD  - Immuno-Oncology Program, Ares Pharmaceuticals, St. Paul, MN 55110, USA.
FAU - Lin, Tara L
AU  - Lin TL
AD  - University of Kansas Cancer Center and Medical Pavillon, University of Kansas, 
      Westwood, KS 66205, USA.
FAU - Mims, Alice S
AU  - Mims AS
AD  - Wexner Medical Center, James Cancer Hospital, The Ohio State University, 
      Columbus, OH 43210, USA.
FAU - Patel, Prapti
AU  - Patel P
AD  - Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA.
FAU - Lee, Cynthia
AU  - Lee C
AD  - Aptevo Therapeutics, Seattle, WA 98121, USA.
FAU - Shahidzadeh, Anoush
AU  - Shahidzadeh A
AD  - Aptevo Therapeutics, Seattle, WA 98121, USA.
FAU - Shami, Paul J
AU  - Shami PJ
AD  - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
FAU - Cull, Elizabeth
AU  - Cull E
AD  - Institute for Translational Oncology Research, Greenville Health System, 
      Greenville, SC 29605, USA.
FAU - Cogle, Christopher R
AU  - Cogle CR
AUID- ORCID: 0000-0001-5422-6863
AD  - Division of Hematology and Oncology, Department of Medicine, College of Medicine, 
      University of Florida, Gainesville, FL 32610, USA.
FAU - Watts, Justin
AU  - Watts J
AD  - Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.
LA  - eng
PT  - Journal Article
DEP - 20210815
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8394899
OTO - NOTNLM
OT  - AML
OT  - APVO436
OT  - CD123
OT  - MDS
OT  - T cells
OT  - bispecific antibody
OT  - clinical study
OT  - leukemia
COIS- T.L.L., P.P., P.J.S., E.C., C.R.C. and J.W. and their institutions received 
      research funding in the form of investigative site awards from Aptevo 
      Therapeutics for conducting the study. F.M.U., A.S. and C.L. received 
      compensation from Aptevo Therapeutics as a consultant. No other disclosures are 
      reported.
EDAT- 2021/08/28 06:00
MHDA- 2021/08/28 06:01
PMCR- 2021/08/15
CRDT- 2021/08/27 01:03
PHST- 2021/07/20 00:00 [received]
PHST- 2021/08/11 00:00 [revised]
PHST- 2021/08/13 00:00 [accepted]
PHST- 2021/08/27 01:03 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/08/28 06:01 [medline]
PHST- 2021/08/15 00:00 [pmc-release]
AID - cancers13164113 [pii]
AID - cancers-13-04113 [pii]
AID - 10.3390/cancers13164113 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Aug 15;13(16):4113. doi: 10.3390/cancers13164113.