A Study of Ruxolitinib in Combination With Ulixertinib in People With Myelofibrosis
Key claim: A phase I/II dose-escalation study is evaluating the safety and efficacy of combining ruxolitinib with ulixertinib (an ERK1/2 inhibitor) in patients with myelofibrosis.
Abstract
The researchers are doing this study to find out whether the combination of ruxolitinib and ulixertinib is a safe and effective treatment for people with myelofibrosis. The researchers will test different doses of ulixertinib to find the highest dose that causes few or mild side effects in participants when given in combination with ruxolitinib.
Why this matters
MAPK/ERK reactivation is one of the proposed mechanisms of persistence and escape from JAK inhibition in myelofibrosis, and pairing ruxolitinib with ulixertinib directly tests whether blocking this downstream node deepens responses in PMF. Within the disease-subtype landscape, this adds another mechanistically distinct rux-combination strategy aimed specifically at the JAKi-suboptimal PMF subpopulation — a recurring theme alongside PI3K, BET, LSD1, XPO1, and Type II JAK2 inhibitor approaches.