Ruben A. Mesa, MD @mpdrc @UTHealthSAMDA #ASCO22 #OncoTwitter @oncoalert Phase III MOMENTUM Study

Ruben A. Mesa, MD @mpdrc @UTHealthSAMDA #ASCO22 #OncoTwit...

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Ruben Mesa, MD, FACP, Executive Director of the Mays Cancer Center, home to UT Health San Antonio, MD Anderson Cancer Center. In this video, he speaks about the ASCO 2022 Abstract - MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor.

Origins:

MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, shown clinical activity in the SIMPLIFY trials for MF symptoms, RBC transfusion requirements (anemia), and spleen volume. This pivotal phase 3 research compared MMB to DAN on major symptom, anemia, and spleen volume endpoints at 24 weeks in MF patients previously treated with a JAK inhibitor (JAKi) (wks).

Methodology:

Eligibility requirements include: primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) 10; Hgb 10 g/dL; prior JAKi for 90 days, or 28 days if RBC transfusions 4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen TSS, palpable spleen, and RBC units were transfused during stratification. The JAKi taper and washout took 21 days. Randomization: MMB 200 mg QD + DAN placebo or DAN 600 mg QD plus MMB placebo for 24 weeks, followed by open-label MMB. Assessments: The patient kept a daily eDiary and had his spleen volume measured with an MRI or CT. TSS response (50 percent reduction from baseline [BL]) rate was the primary goal at week 24. Secondary objectives were RBC transfusion independence (TI) rate, splenic response rate (SRR; 25% reduction in volume from BL), change from BL in TSS, SRR (35 percent reduction from BL), and rate of zero transfusions since BL, all examined sequentially at wk 24.

Findings:

The 24-week randomized treatment (RT) phase was completed by 94 of 130 (72%) MMB patients and 38 of 65 (58%) DAN patients. Hgb levels were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L, respectively. BL TI was 13% (MMB) and 15% (MMB) (DAN). Prior JAKi was ruxolitinib in 195 patients (100%) and fedratinib in 9 patients (5 percent ). All of the primary and secondary endpoints were met (Table). The most common Grade 3 TEAEs in the RT phase of the trial were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8 percent ; DAN, 11 percent ). Gr 3 infections occurred in 15% of MMB patients and 17% of DAN patients. Peripheral neuropathy occurred in 5% of MMB (all Gr 2) and 2% of DAN (Gr 2) patients during the RT phase, and none quit study treatment. Overall, TEAEs caused study drug discontinuation in 18% of MMB and 23% of DAN pts in the RT phase. MMB vs DAN showed a trend toward improved OS up to week 24 (HR=0.506, p=0.0719).

Observations:

MMB was superior than DAN in symptomatic and anemic MF patients for symptom responses, transfusion requirements, and spleen responses, with comparable safety and good survival. MMB may fill a crucial unmet need, especially in MF patients with anemia. NCT04173494 is the clinical trial number.