Navitoclax + Ruxolitinib combination

Current understanding

Navitoclax (oral BCL-2/BCL-XL inhibitor) added to ruxolitinib (JAK1/2 inhibitor) is being evaluated as a combination strategy in myelofibrosis, with the rationale that dual BCL-2/BCL-XL inhibition may overcome apoptotic resistance and deepen responses beyond JAK inhibition alone. A Phase 3 randomized controlled trial (trial-late) is testing whether the combination improves spleen volume reduction and overall outcomes compared with ruxolitinib monotherapy in adult MF patients. Earlier-phase data informed the dosing and safety profile, with thrombocytopenia (BCL-XL on-target) being the principal toxicity to monitor.

Evidence log

• 2026-03-23 — Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis: cross-connection with ruxolitinib: Phase 3 trial uses ruxolitinib monotherapy as the control arm against navitoclax + ruxolitinib, directly linking the new combination page to the ruxolitinib backbone. (novelty: 3)

Open questions

Related