navitoclax + ruxolitinib

A **combination of navitoclax**, an oral small molecule inhibitor of the B-cell lymphoma-2 family proteins (notably BCL-2 and BCL-XL), and **ruxolitinib**, an oral small molecule Janus kinase (JAK) 1 and JAK2 inhibitor. This combination is under investigation primarily for patients with **relapsed or refractory myelofibrosis (MF)**, particularly those with suboptimal response or resistance to ruxolitinib monotherapy. - **Navitoclax** promotes apoptosis of malignant cells by blocking anti-apoptotic BCL-2/BCL-XL proteins, which are overexpressed in myelofibrosis. - **Ruxolitinib** inhibits JAK1/JAK2, reducing inflammatory cytokine signaling and myeloproliferation, key drivers of MF pathogenesis. - The rationale for combination: By targeting both survival pathways (BCL-2/XL) and the disease-driving JAK/STAT pathway, this dual blockade may overcome resistance to JAK inhibitor monotherapy, leading to reductions in spleen volume, symptoms, and disease modification markers such as bone marrow fibrosis. - The combination is not currently approved for any indication but is being studied in global phase II and III trials (e.g., REFINE, TRANSFORM-1, TRANSFORM-2).

Other names

navitoclax plus ruxolitinibnavitoclax and ruxolitinibNAV+RUX