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A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia


He, SZ; Busfield, S; Ritchie, DS; Hertzberg, MS; Durrant, S; Lewis, ID; Marlton, P; McLachlan, AJ; Kerridge, I; Bradstock, KF; Kennedy, G; Boyd, AW; Yeadon, TM; Lopez, AF; Ramshaw, HS; Iland, H; Bamford, S; Barnden, M; DeWitte, M; Basser, R; Roberts, AW
2015-05
2014-11-20
Leuk Lymphoma
Journal Article
56
5
1406-1415
Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-alpha (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses >/= 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy.
Informa
Cancer and Haematology
10.3109/10428194.2014.956316
25248882
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2015-05-19 02:05:28 Last Modified 2016-01-13 02:20:04