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

Cancers

Cynthia Lee¹  Fatih M. Uckun¹  Anoush Shahidzadeh¹  Christopher R. Cogle²  Paul J. Shami³  Elizabeth Cull⁴  Prapti Patel⁵  Justin Watts⁶  Tara L. Lin⁷  Alice S. Mims⁸ 

[1] Aptevo Therapeutics, Seattle, WA 98121, USA;Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA;Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA;Institute for Translational Oncology Research, Greenville Health System, Greenville, SC 29605, USA;Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA;Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA;University of Kansas Cancer Center and Medical Pavillon, University of Kansas, Westwood, KS 66205, USA;Wexner Medical Center, James Cancer Hospital, The Ohio State University, Columbus, OH 43210, USA;

关键词: AML;    MDS;    CD123;    bispecific antibody;    T cells;    leukemia;   

DOI  :  10.3390/cancers13164113

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown