A phase 2 study of itacitinib alone or in combination with low-dose ruxolitinib in patients with myelofibrosis.

Background: The Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has demonstrated efficacy/safety in patients with myelofibrosis; however, not all patients experience optimal and/or stable response, in part owing to dose-limiting toxicities. This phase 2 study evaluated itacitinib (JAK1-selective inhibitor) efficacy/safety alone or combined with low-dose ruxolitinib.

Methods: Cohort A received itacitinib 200 mg once daily (QD) plus ruxolitinib at a previous stable dose (≤15 mg total daily dose). Cohort B (previously ruxolitinib-treated) received itacitinib 600 mg QD alone. The primary endpoint was baseline-to-week 24 spleen volume reduction (SVR).

Results: Twenty-three patients were enrolled (median age, 71.0 years; intermediate-1/-2 risk, 73.9 %; Cohort A, n = 13; Cohort B, n = 10). Mean (standard deviation) percentage SVR from baseline was +6.9 % (27.5 %) and -3.0 % (34.7 %) in Cohorts A and B at week 24 (primary endpoint), and -1.6 % (14.7 %) and -24.6 % (21.7 %) in Cohorts A and B at week 12. SVR from baseline was achieved by 5 and 3 patients in Cohorts A and B at week 24, and by 9 and 7 patients in Cohorts A and B at week 12. Most common treatment-emergent adverse events (TEAEs) were anemia, diarrhea, and fatigue (each n = 8); most common grade ≥ 3 TEAEs were anemia (n = 6), thrombocytopenia (n = 5), fatigue (n = 3), and diarrhea (n = 2).

Conclusions: Overall, 8 of 23 patients enrolled achieved SVR at week 24; larger average changes in SVR at week 12 were observed for itacitinib monotherapy vs. the combination. No unexpected safety signals were observed.