INCB057643 + ruxolitinib

INCB057643 + ruxolitinib is an oral combination therapy consisting of **INCB057643**, a small-molecule bromodomain and extra-terminal (BET) inhibitor, and **ruxolitinib**, a Janus kinase (JAK)1/JAK2 inhibitor. INCB057643 inhibits BET proteins, which are epigenetic regulators of oncogenic gene expression, inflammation, and megakaryocyte differentiation. Ruxolitinib inhibits JAK1/JAK2 signaling, a key pathway in myeloproliferative neoplasms (MPNs) and myelofibrosis (MF). The combination targets both transcriptional programs and cytokine signaling responsible for the pathogenesis of advanced myeloid neoplasms, particularly in patients with MF or those with suboptimal responses to ruxolitinib alone. Clinical studies have shown improved anemia, decreased spleen volume, mitigation of symptom burden, and restoration of hematopoietic differentiation in patients with advanced myelofibrosis when using this combination[3][4][5][6][7].