MPN-478 MOMENTUM: Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated With a JAK Inhibitor

Abstract

© 2022 Elsevier Inc.Background: MMB, a JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity in the MF SIMPLIFY trials. The pivotal phase 3 MOMENTUM study of MF patients previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and splenic endpoints. Methods: Eligibility: Primary or post- essential thrombocythemia (ET)/polycythemia vera (PV) MF; DIPSS High/Int-2/Int-1; MF symptom assessment form total symptom score (TSS) ≥10; hemoglobin <10 g/dL; prior JAKi ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks or grade 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm. Stratification: TSS, palpable spleen, and RBC units transfused. JAKi taper/washout ≥21 days. Randomization: 2:1 MMB 200 mg QD+DAN placebo or DAN 600 mg QD+MMB placebo for 24 weeks. Primary endpoint: TSS response (≥50% reduction from baseline) rate at week 24. Secondary endpoints, assessed sequentially at week 24: transfusion independence (TI) rate, splenic response rate (SRR; ≥25% volume reduction from baseline), TSS change from baseline, SRR (≥35% reduction) and rate of zero transfusions since baseline. Results: 94/130 (72%) MMB and 38/65 (58%) DAN patients completed randomized treatment (RT). Mean baseline TSS were 28 (MMB) and 26 (DAN), hemoglobin levels were 8.1 (MMB) and 7.9 (DAN) g/dL, and median platelets were 97 (MMB) and 94 (DAN) x109/L. Baseline TI was 13% (MMB) and 15% (DAN). Prior JAKi was ruxolitinib in 195 (100%) and fedratinib in 9 (5%) patients. All primary and key secondary endpoints were met: TSS response (24.6% vs 9.2%), TI (30.8% vs 20.0%), SRR25 (40.0% vs 6.2%), TSS change (-9.36 vs -3.13), SRR35 (23.1% vs 3.1%), and zero transfusions (35.4% vs 16.9%). Most common grade ≥3 TEAEs in RT were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN patients in RT. Trend toward improved survival up to week 24 was seen with MMB vs DAN (HR=0.506, p=0.0719). Conclusions: In symptomatic and anemic MF patients, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF patients with anemia.