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CA-4948 is a first-in-class, small-molecule inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), which plays a role in toll-like receptor (TLR) and interleukin-1 receptor signaling pathways. These pathways are known to be dysregulated in non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).1,2 IRAK4 was identified as the most dominant, alternatively-spliced isoform, and the long form of IRAK-4 (IRAK4-L), which encodes a mutant IRAK4 protein with an additional exon, was found to be associated with maximum pathway activation through interaction with the Myddosome protein complex. Inhibiting IRAK4-L activity with CA-4948 resulted in eradicating leukemic activity in AML cells.3
CA-4948 is currently under evaluation as an orally administered monotherapy in a phase I study (NCT04278768) in adults with AML or high-risk MDS. The preliminary results presented during the 62nd American Society of Hematology (ASH) Annual Meeting showed marrow blast reductions and marrow complete responses with no dose-limiting toxicity. More information can be found here.
Initial success in the phase I trial led to the orphan drug designation of CA-4948 by the U.S. Food and Drug Administration (FDA) to treat patients with relapsed or refractory (R/R) AML and MDS.4−6
CA-4948 is also under investigation in a phase I trial (NCT03328078) as a monotherapy or in combination with ibrutinib for adults with R/R NHL.4
P-2001 study: Which patients benefit most from pevonedistat plus azacitidine?
During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the MDS Hub spoke to Mikkael Sekeres, Sylvester Comprehensive Cancer Center, Miami, US,...
How can we improve on current risk stratification in MDS?
During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the MDS Hub spoke to Uwe Platzbecker, University of Leipzig Medical Center, Leipzig, DE. We asked, How can...
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