Phase 3 clinical trials of MMB in patients with myelofibrosis
| Trial name, sample size, and basic eligibility/design . | Major baseline characteristics . | Starting dose of MMB and comparator . | SVR35 at week 24 . | TSS50 at week 24 . | Efficacy for anemia . | AEs (MMB only) . |
|---|---|---|---|---|---|---|
| SIMPLIFY-1 (N = 432)14: MMB vs RUX (1:1) in JAKi-naïve, IPSS int-2/high risk or int-1 risk MF with symptomatic organomegaly or anemia; ANC ≥0.75 × 109/L, plts ≥50 × 109/L. Double blind, double-dummy 24-wk treatment phase→MMB. | 59.5% (MMB) vs 53.5% (RUX) had PMF; ∼80% int-2/high risk; mean TSS 19.4 (MMB) and 17.9 (rux); mean Hgb ∼10.6 g/dL and mean plts ∼301 × 109/L; 68.4% (MMB) and 70% (rux) RBC-TI; 24.7% (MMB) and 24% (rux) RBC-TD | MMB 200 mg daily vs RUX 20 mg bid or per label | 26.5% (MMB) vs 29% (RUX) (ie, noninferior) (P = .011) | 28.4% (MMB) vs 42.2% (RUX) (ie, not noninferior) (P = .98) | RBC-TI at week 24: 66.5% (MMB) vs 49.3% (RUX), nominal P < .001 RBC-TD at week 24: 30.2% (MMB) vs 40.1% (RUX), nominal P = .019 Median rate of RBCs transfused 0 (MMB) vs 0.4 (RUX) U/mo through week 24, nominal P < .001 | Most common gr 3/4: thrombocytopenia (7%), anemia (5.6%), diarrhea, HTN, neutropenia (2.8% each) AEs leading to d/c: 13.1%; leading to dose reduction/hold: 17.8% |
| SIMPLIFY-2 (N = 156)15: MMB vs BAT (89% RUX) 2:1 in DIPSS int-2/high risk or int-1 risk MF with symptomatic organomegaly with prior rux for ≥28 d and heme tox as defined in text; palpable spleen ≥5 cm; no min plt count; no gr ≥2 PN; no washout required | ∼60% had PMF; 78% (MMB) vs 69% (BAT) int-2/high risk; mean TSS ∼19 ; mean Hgb ∼9.4 g/dL; 31% (MMB) vs 37% (BAT) RBC-TI; mean plts 170.8 × 109/L (MMB) vs 126.5 × 109/L (BAT) | MMB 200 mg daily or BAT (RUX in 89% of pts) | 7% (MMB) vs 6% (BAT) (ie, not superior) (P = .9) | 26% (MMB) vs 6% (BAT), nominal P = .0006 | RBC-TI at week 24: 43% (MMB) vs 21% (BAT), nominal P = .0012 RBC-TD at week 24: 50% (MMB) vs 64% (BAT), nominal P = .1 Median rate of RBCs transfused 0.5 (MMB) vs 1.2 (BAT) U/mo through week 24, nominal P = .39 | Most common gr 3/4: anemia (14%), thrombocytopenia (7%), abdominal pain (1%) AEs leading to d/c: 21%; leading to dose reduction/hold: 16% PN: 11% |
| MOMENTUM (N = 195):16 MMB vs danazol 2:1 in DIPSS int/high risk MF with TSS ≥10, Hgb <10, plts ≥25 × 109/L, palpable splenomegaly ≥5 cm or spleen volume ≥450 cm3, and previous treatment with a JAKi (≥90 d or per SIMPLIFY-2 criteria) | 60% (MMB) vs 71% (DAN) had PMF; >90% int-2/high risk; mean TSS ∼28; mean/median Hgb ∼8 g/dL, and mean spleen volume ∼2300 cm3; ∼15% RBC-TI; ∼50% RBC-TD; mean plts 151.7 × 109/L (MMB) vs 130.7 × 109/L (DAN) | MMB 200 mg daily and DAN placebo or DAN 300 mg bid and MMB placebo | 22% (MMB) vs 3% (DAN) (ie, superior) (P = .0011) | 25% (MMB) vs 9% (DAN) (ie, superior) (P = .0095) Mean TSS change at week 24: −11.5 (MMB) vs −3.9 (DAN) (ie, superior) (P = .0014) | RBC-TI at week 24: 30% (MMB) vs 20% (DAN) (ie, noninferior) (P = .0016) Rate of 0 transfusions to week 24: 35% (MMB) vs 17% (DAN) (ie, superior) (P = .0012) | Most common all gr TEAEs: diarrhea (22%), nausea (16%), asthenia (13%) Most frequent gr ≥3 TEAEs: AKI (3%), pneumonia (2%), anemia (61%) AEs leading to d/c: 18% PN (all gr ≤2): 4%. Rates of transaminitis and gr ≥3 thrombocytopenia similar for MMB and DAN. |
| Trial name, sample size, and basic eligibility/design . | Major baseline characteristics . | Starting dose of MMB and comparator . | SVR35 at week 24 . | TSS50 at week 24 . | Efficacy for anemia . | AEs (MMB only) . |
|---|---|---|---|---|---|---|
| SIMPLIFY-1 (N = 432)14: MMB vs RUX (1:1) in JAKi-naïve, IPSS int-2/high risk or int-1 risk MF with symptomatic organomegaly or anemia; ANC ≥0.75 × 109/L, plts ≥50 × 109/L. Double blind, double-dummy 24-wk treatment phase→MMB. | 59.5% (MMB) vs 53.5% (RUX) had PMF; ∼80% int-2/high risk; mean TSS 19.4 (MMB) and 17.9 (rux); mean Hgb ∼10.6 g/dL and mean plts ∼301 × 109/L; 68.4% (MMB) and 70% (rux) RBC-TI; 24.7% (MMB) and 24% (rux) RBC-TD | MMB 200 mg daily vs RUX 20 mg bid or per label | 26.5% (MMB) vs 29% (RUX) (ie, noninferior) (P = .011) | 28.4% (MMB) vs 42.2% (RUX) (ie, not noninferior) (P = .98) | RBC-TI at week 24: 66.5% (MMB) vs 49.3% (RUX), nominal P < .001 RBC-TD at week 24: 30.2% (MMB) vs 40.1% (RUX), nominal P = .019 Median rate of RBCs transfused 0 (MMB) vs 0.4 (RUX) U/mo through week 24, nominal P < .001 | Most common gr 3/4: thrombocytopenia (7%), anemia (5.6%), diarrhea, HTN, neutropenia (2.8% each) AEs leading to d/c: 13.1%; leading to dose reduction/hold: 17.8% |
| SIMPLIFY-2 (N = 156)15: MMB vs BAT (89% RUX) 2:1 in DIPSS int-2/high risk or int-1 risk MF with symptomatic organomegaly with prior rux for ≥28 d and heme tox as defined in text; palpable spleen ≥5 cm; no min plt count; no gr ≥2 PN; no washout required | ∼60% had PMF; 78% (MMB) vs 69% (BAT) int-2/high risk; mean TSS ∼19 ; mean Hgb ∼9.4 g/dL; 31% (MMB) vs 37% (BAT) RBC-TI; mean plts 170.8 × 109/L (MMB) vs 126.5 × 109/L (BAT) | MMB 200 mg daily or BAT (RUX in 89% of pts) | 7% (MMB) vs 6% (BAT) (ie, not superior) (P = .9) | 26% (MMB) vs 6% (BAT), nominal P = .0006 | RBC-TI at week 24: 43% (MMB) vs 21% (BAT), nominal P = .0012 RBC-TD at week 24: 50% (MMB) vs 64% (BAT), nominal P = .1 Median rate of RBCs transfused 0.5 (MMB) vs 1.2 (BAT) U/mo through week 24, nominal P = .39 | Most common gr 3/4: anemia (14%), thrombocytopenia (7%), abdominal pain (1%) AEs leading to d/c: 21%; leading to dose reduction/hold: 16% PN: 11% |
| MOMENTUM (N = 195):16 MMB vs danazol 2:1 in DIPSS int/high risk MF with TSS ≥10, Hgb <10, plts ≥25 × 109/L, palpable splenomegaly ≥5 cm or spleen volume ≥450 cm3, and previous treatment with a JAKi (≥90 d or per SIMPLIFY-2 criteria) | 60% (MMB) vs 71% (DAN) had PMF; >90% int-2/high risk; mean TSS ∼28; mean/median Hgb ∼8 g/dL, and mean spleen volume ∼2300 cm3; ∼15% RBC-TI; ∼50% RBC-TD; mean plts 151.7 × 109/L (MMB) vs 130.7 × 109/L (DAN) | MMB 200 mg daily and DAN placebo or DAN 300 mg bid and MMB placebo | 22% (MMB) vs 3% (DAN) (ie, superior) (P = .0011) | 25% (MMB) vs 9% (DAN) (ie, superior) (P = .0095) Mean TSS change at week 24: −11.5 (MMB) vs −3.9 (DAN) (ie, superior) (P = .0014) | RBC-TI at week 24: 30% (MMB) vs 20% (DAN) (ie, noninferior) (P = .0016) Rate of 0 transfusions to week 24: 35% (MMB) vs 17% (DAN) (ie, superior) (P = .0012) | Most common all gr TEAEs: diarrhea (22%), nausea (16%), asthenia (13%) Most frequent gr ≥3 TEAEs: AKI (3%), pneumonia (2%), anemia (61%) AEs leading to d/c: 18% PN (all gr ≤2): 4%. Rates of transaminitis and gr ≥3 thrombocytopenia similar for MMB and DAN. |
AE, adverse event; AKI, acute kidney injury; ANC, absolute neutrophil count; BAT, best available therapy; bid, twice daily; DAN, danazol; d/c, discontinuation; DIPSS, Dynamic International Prognostic Scoring System; gr, grade; heme tox, hematologic toxicity; Hgb, hemoglobin; HTN, hypertension; int, intermediate; IPSS, International Prognostic Scoring System; JAKi, JAK inhibitor; min, minimum; MMB, momelotinib; plts, platelets; PMF, primary myelofibrosis; PN, peripheral neuropathy; RBC-TD, red blood cell transfusion dependent; RBC-TI, red blood cell transfusion independent/independence; RUX, ruxolitinib; SVR35, spleen volume reduction of ≥35%; TEAE, treatment-emergent adverse event; TSS, total symptom score; TSS50, TSS reduction of ≥50%.