Phase 3 randomized trial of momelotinib (MMB) versus best available therapy (BAT) in patients with myelofibrosis (MF) previously treated with ruxolitinib (RUX).

Authors

null

Claire N. Harrison

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom

Claire N. Harrison , Alessandro M. Vannucchi , Uwe Platzbecker , Francisco Cervantes , Vikas Gupta , David Lavie , Francesco Passamonti , Elliott F. Winton , Hua Dong , Jun Kawashima , Julia D. Maltzman , Jean-Jacques Kiladjian , Srdan Verstovsek

Organizations

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, University of Florence, Florence, Italy, Medizinische Fakultät Carl Gustav Carus, Technische Universität, Dresden, Germany, Hospital Clínic de Barcelona, Barcelona, Spain, Princess Margaret Cancer Centre, Toronto, ON, Canada, Hadassah Hebrew University Medical Center, Jerusalem, Israel, University of Insubria, Varese, Italy, Emory University School of Medicine, Atlanta, GA, Gilead Sciences, Inc., Foster City, CA, Saint-Louis Hospital (AP-HP) and Paris Diderot University, Paris, France, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

Pharmaceutical/Biotech Company

Background: MMB, an oral JAK inhibitor, has been shown in early trials to reduce spleen volume, improve disease associated symptoms (Sx) and improve RBC transfusion requirements in patients (pts) with MF. This study of previously RUX treated pts with MF tested the superiority of MMB vs BAT in splenic volume reduction, Sx amelioration, and transfusion requirement at 24 weeks. Methods: Eligibility included primary or post-ET/PV MF; DIPSS high risk, Int-2, or symptomatic Int-1; prior RUX ≥4 weeks who either required transfusions or dose reduction to <20 mg BID with at least one of Gr ≥3 thrombocytopenia, anemia, or bleed; palpable spleen ≥5cm; and no Gr ≥2 peripheral neuropathy. Stratification was by transfusion dependency and baseline TSS (modified MPN-SAF Total Sx Score) <18 or ≥18. Pts were randomized 2:1 to 24 weeks of open-label MMB 200 mg QD or BAT. Assessments included spleen volume by MRI, and patient-reported Sx using a daily eDiary for TSS. 1° endpoint was splenic response rate (SRR; ≥35% reduction in volume from baseline). 2°endpoints, evaluated sequentially, were rates of TSS response (TSS RR; ≥50% reduction from baseline), RBC transfusion, RBC transfusion independence (TI) and RBC transfusion dependence (TD). Results: 73 of 104 (70%) and 40 of 52 (77%) pts receiving MMB or BAT, respectively, completed the 24 week randomized treatment phase. BAT for 88% of pts included RUX, and 27% of pts were on RUX in combination with other drugs. Efficacy results are in Table. The most common Gr ≥3 adverse events in MMB pts were anemia (13%) and thrombocytopenia (7%), and in BAT pts, anemia (13%), thrombocytopenia (6%) and abdominal pain (6%); treatment emergent peripheral neuropathy occurred in 11 (11%) of MMB (1 Gr3) and in no BAT pts. Conclusions: In previously RUX-treated patients with MF, 24 weeks of MMB was not superior to BAT for SRR, but significantly better in improving disease related symptoms and transfusion independence. Clinical trial information: NCT02101268

EndpointsMMBBATp-value
SRR, %6.75.80.90
TSS RR, %26.25.9<0.001a
Transfusion rate (units/month), med0.51.20.39
TI rate, %43.321.20.001a
TD rate, %50.063.50.10

a p-values nominally significant

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Myeloproliferative Neoplasms (MPN) and Mast Cell Disorders

Clinical Trial Registration Number

NCT02101268

Citation

J Clin Oncol 35, 2017 (suppl; abstr 7001)

DOI

10.1200/JCO.2017.35.15_suppl.7001

Abstract #

7001

Abstract Disclosures