Phase 3 trial of momelotinib (MMB) vs ruxolitinib (RUX) in JAK inhibitor (JAKi) naive patients with myelofibrosis (MF).

7000Background: MMB, an oral JAKi, has been shown in early trials to reduce spleen volume, improve disease associated symptoms (Sx) and improve RBC transfusion (Tx) requirements in patients (pts) with MF. This study was designed to test non-inferiority of MMB vs RUX in splenic volume reduction and Sx amelioration, and superiority in Tx requirement, in JAKi naive MF pts. Methods: Eligibility: MF, IPSS high risk, Int-2, or symptomatic Int-1; palpable spleen ≥5cm; platelets ≥ 50 K/μl, and no Gr ≥2 peripheral neuropathy (PN). Stratification by Tx dependency and platelets ( 200 K/μl). Pts were randomized 1:1 to 24 wks of MMB 200 mg qd + RUX placebo or RUX 20 mg bid (or modified per label) + MMB placebo, after which all pts could receive open label MMB. Assessments: spleen volume by MRI, and pt reported Sx using a daily eDiary of modified MPN-SAF Total Sx Score (TSS). Primary endpoint was splenic response rate (SRR; ≥35% reduction in volume from baseline) at 24 wks. Secondary endpoints, evalua...