ASH 2025 | Nuvisertib + momelotinib in patients with R/R MF: Phase I/II findings

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, the MPN Hub was pleased to speak with Claire Harrison, Guy’s and St Thomas’ NHS Foundation Trust, London, UK. We asked, What are the latest findings from the phase I/II study of nuvisertib in combination with momelotinib in patients with relapsed/refractory myelofibrosis (R/R MF)? 

In this interview, Harrison discusses key findings from Arm 3 of the trial (NCT04176198), which enrolled patients who had been previously treated with a Janus kinase inhibitor (JAKi) other than momelotinib. The study aimed to identify the recommended phase II dose (RP2D) of nuvisertib when administered in combination with momelotinib, and to assess the safety, clinical activity (spleen volume reduction [SVR] and total symptom score [TSS] improvement), and pharmacokinetics and pharmacodynamic markers (including cytokines and bone marrow fibrosis). 

Key points

• As of October 15, 2025, 18 patients were enrolled at four twice-daily (BID) dose levels of nuvisertib; 240 mg (n = 4), 360 mg (n = 8), 480 mg (n = 5) and 720 mg (n = 1), all in combination with momelotinib 200 mg daily (QD).
• The combination of nuvisertib and momelotinib appeared to be well tolerated, with no new safety signals observed. The most common treatment-related adverse events (TRAEs) were diarrhea, and nausea and vomiting, which were transient and manageable with supportive care.
• SVR ≥25% (SVR25) was achieved in 50% of patients at Week 24 and at any time on the study in those receiving nuvisertib 360 mg BID or higher.
• A TSS reduction of ≥50% (TSS50) was achieved in 42% at Week 24 and in 58% of patients at any time on the study in those receiving nuvisertib 360 mg BID or higher.
• A hemoglobin response was observed in 56% of patients and platelet counts were stable.
• These preliminary data support the ongoing clinical development of nuvisertib in combination with momelotinib for the treatment of patients with R/R MF. 

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