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Article

A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

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Aptevo Therapeutics, Seattle, WA 98121, USA
2
Immuno-Oncology Program, Ares Pharmaceuticals, St. Paul, MN 55110, USA
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University of Kansas Cancer Center and Medical Pavillon, University of Kansas, Westwood, KS 66205, USA
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Wexner Medical Center, James Cancer Hospital, The Ohio State University, Columbus, OH 43210, USA
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Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA
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Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
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Institute for Translational Oncology Research, Greenville Health System, Greenville, SC 29605, USA
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Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA
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Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Ada Funaro
Cancers 2021, 13(16), 4113; https://doi.org/10.3390/cancers13164113
Received: 20 July 2021 / Revised: 11 August 2021 / Accepted: 13 August 2021 / Published: 15 August 2021
(This article belongs to the Special Issue Acute Myeloid Leukemia (AML))
AML is a common form of blood cancer in adults. This study was undertaken to evaluate if AML patients who have failed the available standard treatment options could tolerate and potentially benefit from a new form of therapy. This new therapy activates patients’ own immune system against AML cells. The findings from this research may provide the foundation for a potentially more effective future form of standard therapy that is less likely to fail.
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. View Full-Text
Keywords: AML; MDS; CD123; bispecific antibody; T cells; leukemia; clinical study; APVO436 AML; MDS; CD123; bispecific antibody; T cells; leukemia; clinical study; APVO436
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MDPI and ACS Style

Uckun, F.M.; Lin, T.L.; Mims, A.S.; Patel, P.; Lee, C.; Shahidzadeh, A.; Shami, P.J.; Cull, E.; Cogle, C.R.; Watts, J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers 2021, 13, 4113. https://doi.org/10.3390/cancers13164113

AMA Style

Uckun FM, Lin TL, Mims AS, Patel P, Lee C, Shahidzadeh A, Shami PJ, Cull E, Cogle CR, Watts J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers. 2021; 13(16):4113. https://doi.org/10.3390/cancers13164113

Chicago/Turabian Style

Uckun, Fatih M., Tara L. Lin, Alice S. Mims, Prapti Patel, Cynthia Lee, Anoush Shahidzadeh, Paul J. Shami, Elizabeth Cull, Christopher R. Cogle, and Justin Watts. 2021. "A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome" Cancers 13, no. 16: 4113. https://doi.org/10.3390/cancers13164113

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