EXCEED-ET phase IIb trial: Ropeginterferon alfa-2b in ET across driver mutations

Results from the single-arm, multicenter, phase IIb EXCEED-ET (NCT05482971) trial, evaluating ropeginterferon alfa-2b in 91 North American patients with essential thrombocythemia (ET), who were either treatment-naïve or hydroxyurea (HU)-pretreated, were published in The Lancet Regional Health – Americas by Reeves et al. The primary endpoint was durable, modified European LeukemiaNet (ELN) response at both Months 10 and 13. 

Key data: An ELN response at both Months 10 and 13 was achieved in 60.2% of patients (95% confidence interval [CI], 49.0–71.4). Median time to hematologic response was 8.4 weeks (95% CI, 8.1–11.9). Molecular response rates at Month 13 were 35.0%, 16.0%, and 25.0% in patients with JAK2V617F, CALR, and MPL mutations, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 27.5% of patients and most commonly included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increases (4.4%), neutrophil count decrease (4.4%), fatigue (3.3%), and lymphocyte count decrease (3.3%); there were no Grade 5 TEAEs. 

Key learning: Ropeginterferon alfa-2b demonstrated durable hematologic responses and meaningful molecular responses across JAK2V617F, CALR, and MPL driver mutations in a North American population, with a manageable safety profile consistent with known interferon-α therapy, supporting its use regardless of prior treatment or driver mutation status.