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Tagraxofusp + pacritinib is an investigational combination therapy being evaluated for the treatment of intermediate-II or higher myelofibrosis, particularly in patients who have failed or are ineligible for standard JAK inhibitor therapy. Tagraxofusp (Elzonris) is a recombinant fusion protein consisting of human interleukin-3 (IL-3) fused to a truncated diphtheria toxin; it targets the IL-3 receptor (CD123) expressed on malignant myeloid cells, delivering the toxin to inhibit protein synthesis via ADP-ribosylation of elongation factor 2. Pacritinib (Vonjo) is an oral small molecule inhibitor of Janus kinase 2 (JAK2) and interleukin-1 receptor-associated kinase 1 (IRAK1), approved for myelofibrosis patients with severe thrombocytopenia. The combination is being studied by the University of Kansas Medical Center in the TAGPAC pilot Phase II trial (NCT06414681) to leverage the targeted cytotoxicity of tagraxofusp against CD123-positive cells alongside the JAK2/IRAK1 pathway inhibition of pacritinib.
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