Phase I/II trial: Tagraxofusp in myelofibrosis

Results from a phase I/II trial (NCT02268253) of tagraxofusp, a first-in-class CD123-targeted therapy, in patients with myelofibrosis (MF), were recently published by Yacoub et al. in Blood Neoplasia. The study included patients with treatment-naïve (n = 5) and relapsed/refractory [R/R] MF (n = 25). The primary objectives were to determine the maximum tolerated dose (MTD), safety, and efficacy.

Key data: The recommended phase II dose (RP2D) was 12 μg/kg/day, with 36 and 30 patients treated at this dose and evaluable for safety and efficacy, respectively. The most frequent Grade ≥3 treatment-emergent adverse events (TEAEs) were anemia (22%), thrombocytopenia (19%), and dyspnea (11%). Capillary leak syndrome occurred in 11% of patients, all during Cycle 1 with resolution in all patients. Of 18 patients (treatment-naïve, n = 2; R/R, n = 16), two patients with R/R MF had spleen volume reduction ≥35% (SVR35). In both the treatment-naïve and R/R groups, 40% of patients had total symptom score reduction ≥50% (TSS50).

Key learning: Tagraxofusp monotherapy was well tolerated, without cumulative myelotoxicity, and resulted in symptom score improvements, warranting further investigation in combination therapy.