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Enrollment to the pivotal phase 3 MOMENTUM trial, which is evaluating the novel JAK1/2 and ACVR1/ALK2 inhibitor momelotinib vs danazol in patients with symptomatic myelofibrosis and anemia, has completed.
Enrollment to the pivotal phase 3 MOMENTUM trial (NCT04173494), which is evaluating the novel JAK1/2 and ACVR1/ALK2 inhibitor momelotinib vs danazol in patients with symptomatic myelofibrosis and anemia, has completed, according to the sponsor of the study, Sierra Oncology, Inc.1
The study enrolled 195 patients, after a planned enrollment of 180 patients, across 21 countries. Pending positive topline results from the trial, Sierra Oncology intends to submit a new drug application for momelotinib to the FDA in the second half of 2022.
“The completion of accrual to the MOMENTUM study investigating momelotinib is an important milestone for advancing treatment options for patients with myelofibrosis,” Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, said to OncLive® in a statement. “We hope the outcomes from the MOMENTUM study will further validate the significant [effect] of momelotinib as an important option for improving splenomegaly, symptoms, cytopenias, and even overall survival for patients with myelofibrosis in the second-line setting.”
Momelotinib is a selective, oral JAK1/2 and ACVR1/ALK2 inhibitor that has demonstrated clinical activity against myelofibrosis, which results from dysregulated JAK-STAT signaling. Moreover, the agent is a potential treatment for myelofibrosis-related constitutional symptoms, splenomegaly, and progressive anemia.
MOMENTUM is a randomized, double-blind, global trial in which patients with primary myelofibrosis, post–polycythemia vera (PV) myelofibrosis, or post–essential thrombocythemia (ET) myelofibrosis were randomized 2:1 to once-daily, oral momelotinib vs twice-daily, oral danazol.2 Placebos to match danazol and momelotinib, respectively, will also be administered.
Patients who receive momelotinib may continue on the agent in the open-label, extended treatment period until week 204, representing a treatment period of approximately 4 years. In the danazol arm, patients who are responding to treatment may continue for up to 48 weeks.
Patients who receive danazol are able to cross over to the momelotinib arm at the end of week 24 if they complete the randomized treatment period or discontinue treatment with danazol but continue study assessments and don’t receive prohibited therapies. Additionally, patients are eligible to cross over at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographic symptomatic splenic progression.
Investigators aim to determine whether momelotinib is superior to danazol in treating and reducing disease-related symptoms, the need for blood transfusions, and splenomegaly in this patient population.
Total symptom score (TSS) response rate at week 24 per Myelofibrosis Symptom Assessment Form version 4.0 will serve as the primary end point of the study. Key secondary end points include transfusion independence status at week 24 and splenic response rate at week 24.
Inclusion criteria stated that patients had to be 18 years or older with a confirmed diagnosis of primary myelofibrosis, post–PV myelofibrosis, or post–ET myelofibrosis to be eligible for enrollment. Additionally, patients had to have symptomatic disease as defined by a TSS of 10 or more units at screening, and anemia as defined as hemoglobin less than 10 g/dL at baseline.
Patients were previously treated with an approved JAK inhibitor for primary myelofibrosis or post-PV/ET myelofibrosis for 90 days or more. If treatment with the JAK inhibitor was complicated by a blood transfusion of 4 or more units in 8 weeks or grade 3 or 4 thrombocytopenia, anemia, or hematoma, patients who received treatment for 28 days or more were still eligible for enrollment.
Patients had baseline splenomegaly and high-, intermediate-2, or intermediate-1–risk myelofibrosis, and no planned allogenic stem cell transplant.
Exclusion criteria stated that patients who had prior momelotinib were not eligible to enroll. Additionally, patients who received approved JAK inhibitor therapies, such as ruxolitinib (Jakafi) or fedratinib (Inrebic), active anti-myelofibrosis therapy, or potent cytochrome P450 3A4 inducers within 1 week prior to randomization; investigational agents or erythropoiesis stimulating agents within 4 weeks prior to randomization; or danazol or splenic irradiation within 3 months prior to randomization were ineligible.
“This is an important milestone for Sierra [Oncology] on our path to becoming a commercial organization. The team has demonstrated the ability to execute a global late-stage development trial, even during a pandemic,” said Stephen Dilly, MBBS, PhD, president and chief executive officer of Sierra Oncology.1
“Oversubscribing the trial and completing enrollment at an accelerated pace in the midst of a global crisis supports our hypothesis that physicians want new options for a significant unmet need that momelotinib may address. We look forward to topline results early next year and to continue working with the FDA and global regulatory authorities to bring this therapy to market as quickly as possible,” Dilly added.
Topline data from the MOMENTUM trial are anticipated during quarter 1 of 2022.