Phase 1b study of ABBV-744, a novel, selective BET inhibitor, as monotherapy for patients with myelofibrosis

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: SVR35: 24% at week 12, 33% at week 24; TSS50: 29% at week 12, 19% at week 24

• Primary Outcome: Safety assessment: 100% of patients (21/21) experienced treatment-emergent adverse events; 52% (11/21) experienced dose-limiting toxicities

• Nnt Or Sensitivity: Most common DLTs: thrombocytopenia (33%) and anemia (24%)

• Confidence Interval: Not reported

Clinical Application

Limited by high toxicity profile; requires careful patient selection and monitoring in specialized hematology centers Would require TGA approval and PBS listing; limited to tertiary hematology centers with MF expertise; complements existing JAK inhibitor options but safety profile concerning Heavily pretreated myelofibrosis patients with prior JAK inhibitor exposure who have limited treatment options

Abstract

Janus kinase inhibitors (JAKi) are standard of care for patients with myelofibrosis (MF) but can be associated with treatment-limiting cytopenias and do not modify underlying disease. Novel treatments targeting other clinically relevant pathways are needed. Inhibitors of bromodomain (BD) and extraterminal domain (BET) proteins are a promising class of drugs that have demonstrated the ability to modulate key pathways involved in inflammation, fibrosis, and apoptosis. ABBV-744 is a novel small molecule that targets the BDII of BET proteins and has previously been shown to be well tolerated when administered daily at doses of 120 and 180 mg to patients with acute myeloid leukemia. We report the outcomes of a multicenter, open-label phase 1b study of ABBV-744 in patients with MF who received ≥1 previous lines of therapy, including a JAKi. The primary objective was safety, including dose-limiting toxicities (DLTs). Secondary end points included a reduction in spleen volume of ≥35% (SVR35), ≥50% reduction in total symptom score (TSS50), objective response rate, and pharmacokinetics. All 21 patients experienced at least 1 treatment-emergent adverse event, and 11 patients experienced a DLT. The most common events leading to DLTs were thrombocytopenia (33%) and anemia (24%). SVR35 was attained in 24% of patients at week 12 and 33% at week 24. TSS50 was reported for 29% of patients at 12 weeks and 19% at week 24. These outcomes are noteworthy in this heavily pretreated population considering the advanced disease state and limited treatment options for this patient population. This trial was registered at www.clinicaltrials.gov as NCT04454658.

References

1. 1.Mascarenhas, J., Fogliatto, L., Green, S., Corvalan, I., Traer, E., Kirito, K., Chuah, H., Sakatoku, K., Hoeg, R., Khawandanah, M., Lavie, D., Hunter, Z., Quinn, D., Wang, Y., Harb, J., Zha, J., Malyankar, U., & Ritchie, E. (2026). Phase 1b study of ABBV-744, a novel, selective BET inhibitor, as monotherapy for patients with myelofibrosis. *Blood Advances*. https://doi.org/10.1182/bloodadvances.2025018695