Phase III Study of Momelotinib Launched to Evaluate Efficacy in Patients With Myelofibrosis

Srdan Verstovsek, MD, PhD

Srdan Verstovsek, MD, PhD

The new phase III MOMENTUM clinical trial (NCT04173494), which is evaluating the efficacy of momelotinib, a JAK1, JAK2 and ACVR1 inhibitor, versus active comparator danazol (Danocrine) in patients with symptomatic and anemic myelofibrosis (MF), was recently launched globally, according to a press release from Sierra Oncology.¹

MOMENTUM is a randomized and double-blind trial in which investigators plan to enroll 180 patients who were previously treated with a JAK inhibitor. Srdan Verstovsek, MD, PhD, has been selected as the chief investigator for the study.¹

“I am pleased to act as Chief Investigator for this important global trial for the MF patient community. JAK inhibitors remain the cornerstone of MF treatment but new options in this class are needed for the majority of patients who have difficulty tolerating the currently approved agents due to the cytopenias they can exacerbate or induce,” said Verstovsek, professor, Department of Leukemia, University of Texas MD Anderson Cancer Center, in a statement. “Momelotinib could become a suitable alternative for many patients previously treated with a JAK inhibitor due to its ability to positively address all 3 hallmarks of MF - symptoms, anemia and an enlarged spleen. Critically, momelotinib has consistently demonstrated positive anemia benefits in its prior clinical trials. This anemia benefit is biologically-driven, via potent inhibition of the ACVR1/hepcidin axis, a mechanism that is unique in the JAK inhibitor class.”

Patients in the study will be randomized 2:1 to receive either momelotinib tablets orally once daily plus danazol capsules orally twice daily or danazol alone. The dosage for each drug is yet to be determined. The study also allows for crossover from danazol to momelotinib after 24 weeks of treatment.¹

The primary endpoint of MOMENTUM is the total symptom score (TSS) response rate at week 24, which will be measured through the MF Symptom Assessment Form version 4.0. This endpoint is defined as the proportion of patients who achieve a ≥ 50% reduction in TSS over the 28 days prior to the 24-week cutoff time. The trial is also looking at 2 secondary endpoints, including transfusion independence status and splenic response rate.¹

To enroll in the study, patients must be aged 18 years or older with a confirmed post-polycythemia vera (PV) MF or post-essential thrombocythemia (ET) MF, and patients must either be symptomatic or anemic. Patients are also required to have undergone treatment with at least 1 JAK inhibitor for either form of MF, be intermediate-1 to high-risk and have acceptable laboratory assessments. These patients could not have an allogeneic stem cell transplant planned.²

The study excluded individuals with who were previously treated with momelotinib at any time or a JAK inhibitor within 2 weeks prior to the trial start date, active anti-MF therapy within 2 weeks prior to starting the study, potent cytochrome P450 3A4 within 1 week of the trail start date, an investigational agent within 4 weeks, a erythropoiesis-stimulating agent within 4 weeks, danazol within 3 months, splenic irradiation within months or current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin. Having a history of prostate cancer unless localized or a prostate-specific antigen > 4 ng/mL or unsuitable for spleen volume measurements will also result in exclusion from the study. MOMENTUM has several other exclusion criteria which include other cancers or comorbidities.²

MOMENTUM follows a string of phase III studies using momelotinib to treat MF. For example, the phase III SIMPLIFY-1 study (NCT01969838) of momelotinib versus ruxolitinib (Jakafi) in patients with MF, post-PV, or post-ET MF demonstrated a significant reduction in splenomegaly and improvements in constitutional symptoms at 24 weeks. Momelotinib also demonstrated a higher rate of transfusion independence (P< 0.001) and lower rates of transfusion dependence (P= 0.019), according to dynamic and time-to-events analyses that Sierra Oncology plans to present at the 2019 American Society of Hematology (ASH) Annual Meeting and Exposition, according to a November press release.³

&ldquo;MOMENTUM is designed to confirm the array of benefits observed in prior Phase III studies, where momelotinib demonstrated a unique ability to improve anemia and reduce transfusion dependency in patients with MF, while also providing clinically comparable benefits on constitutional symptoms and enlarged spleens to other JAK inhibitors,&rdquo; Barbara Klencke, MD, chief development officer, Sierra Oncology, stated in the press release.

Klencke also announced that top-line data from the phase III MOMENTUM trial are expected in the fourth quarter of 2021.¹The estimated study completion date is June 2022.²

References

1. Sierra Oncology Launches the MOMENTUM Phase 3 Clinical Trial for Patients with Myelofibrosis [press release]. Vancouver, British Columbia: Sierra Oncology; November 20, 2019. https://prn.to/2LxCoRO. Accessed December 9, 2019.
2. A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM). Clinicaltrials.gov. https://bit.ly/2YqZ77B. Accessed December 9, 2019.
3. Sierra Oncology to Report New Analyses Supporting Momelotinib's Anemia Benefits at ASH 2019 [press release]. Vancouver, British Columbia: Sierra Oncology; November 6, 2019.https://bit.ly/2LAAeRt. Accessed December 9, 2019.