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Targeting CD123 with tagraxofusp in patients with poor prognosis following a JAKi treatment | Recent results from a phase I/II trial

Aug 20, 2020

Relapse or treatment failure following treatment with a Janus kinase inhibitor (JAKi) has been associated with poor prognosis in patients with myelofibrosis (MF), resulting in a median overall survival of approximately 2 years and leaving these patients with no approved treatment options. Other poor prognosis factors include thrombocytopenia, monocytosis, accelerated phase or clonal evolution. Naveen Pemmarajuand colleagues are currently investigating tagraxofusp (SL-401), a novel CD123-targeted therapy, in a phase I/II study ( NCT02268253 ) to evaluate safety and efficacy in patients with chronic myelomonocytic leukemia (CMML) or MF where overexpression of CD123 has been observed. Recent results in patients with MF have been presented during the virtual edition of the 25th European Hematology Association (EHA) Annual Congress, and here we summarize the phase I results. 1

Tagraxofusp has been recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients ≥ 2 years of age. 2

Study design 1

  • Total number of patients with MF = 32
  • Multicenter, open-label, single-arm trial comprising two stages:
  • Stage 1 (dose escalation, n = 4, completed) to identify optimal dose for stage 2
  • Dosing schedule: daily 15-minute intravenous infusion on Days 1–3 of a 21-day cycle (Cycle 1 to 4); 28-day cycle (Cycles 5 to 7); 42-day cycles thereafter
  • Dose escalation: infusion at doses of 7, 9, or 12 µg/kg
  • Stage 2 (n = 28, ongoing) to further evaluate safety and efficacy
  • Dosing schedule: daily 15-minute intravenous infusion of 12 µg/kg as above  
  • Inclusion criteria: Age ≥ 18 years, Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, adequate organ function at baseline
  • Revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) Response Criteria were used for response criteria in MF (2013)

Patient characteristics

Median age was 69.5 years (range 54–87), and baseline monocytosis (≥ 1 × 10 9/L) was observed in 25% of patients. Median number of previous therapies was 2 (range 1–4), 13 patients received ≥ 3 lines of therapies previously and 22 (69%) patients received previous treatment with JAKi while two patients had received an allogeneic stem cell transplant. 78% of patients had splenomegaly at baseline, 16% had hepatomegaly. A summary of patient characteristics is presented in Table 1, below. 

Table 1.Patient characteristics 1

DIPSS, Dynamic International Prognostic Scoring System; MF, myelofibrosis; PMF, primary MF; Post-ET, post essential thrombocythemia; Post-PV, post polycythemia vera; WBC, white blood cells

Platelets ( × 10 9/L), median (range)

> 100, n

> 50–100, n

≥ 20–50, n

< 20, n

57.5 (5–579)





Hemoglobin (g/dL), median (range)

8.6 (6.0–15.2)

WBC ( × 10 9/L), median (range)

11.9 (1.4–86.9)

Myelofibrosis type, n


Post-PV MF

Post-ET MF





DIPSS-plus risk score, n








Driver mutations, n

JAK2 V617F











Results 1


The results of safety assessment are provided in Table 2, below.

Table 2.Most common (≥ 10%) grade ≥ 3 treatment-related adverse events 1

AST, aspartate aminotransferase; CLS, capillary leak syndrome; TRAE, treatment-related adverse event


All grades, n (%)

Grade ≥3, n (%)


4 (14)

4 (13)


4 (14)

3 (9)


3 (9)

2 (6)


8 (25)

1 (3)

Increased AST

3 (9)

1 (3)


3 (9)

1 (3)

Of 32 patients, 28 discontinued treatment and the primary reasons included disease progression (n = 8), adverse event (n = 5), physician decision (n = 4), withdrawal (n = 4), other medical conditions (n = 3), and requiring allogeneic stem cell transplant (n = 1). Three patients died due to intracranial hemorrhage, gastric perforation, and septic shock (n = 1 each), and death events were considered not related to the study drug.


Efficacy assessment was carried out at the end of Cycle 4. Spleen size measurements were done by a physical exam, and the results are summarized in Table 3, below.

Table 3 .  Spleen size reductions among patients 1

BCM, below costal margin

Type of patient

Baseline splenomegaly, n

All spleen reductions, n (%)

≥ 50% reduction, n

Patients with splenomegaly ≥ 5 cm BCM at baseline


10 (56)


Patients with thrombocytopenia

Platelets < 100 × 10 9/L

Platelets < 50 × 10 9/L





8 (62)

4 (57)




Patients with monocytosis


4 (80)


  Of 24 evaluable patients, 11 (46%) achieved reduced symptom burden with three patients achieving total symptom score reduction based on the IWG-MRT 2013 MF response criteria at 24 weeks. There was a possible correlation between reductions in spleen size and total symptom score responses.

Based on the IWG 2013 assessment

  • 56% of patients had stable disease (in 75% of patients with monocytosis, 43% of patients with platelet levels below 20 × 10 9/L at baseline, and 67% of patients with accelerated phase MF)
  • four patients reported additional clinical improvements for anemia, spleen size and/or symptom score
  • One patient achieved a spleen size response 

At a median follow-up of 27 months (0.6–50.3 months), median overall survival was 30.5 months (0.6–50.3 months). While five patients received treatment for more than 12 months, one patient is still on treatment beyond 24 months. 


In patients with poor prognosis MF including a subset of patients with thrombocytopenia, monocytosis, accelerated phase, and clonal evolution, tagraxofusp has shown clinical efficacy with a predictable safety profile. The ongoing Stage 2 cohort is expanding to investigate the safety and efficacy in patients with relapsed/refractory MF. Further development of tagraxofusp in MF with poor prognosis features such as thrombocytopenia, monocytosis, and accelerated phase, is under evaluation.

  1. Pemmaraju N, Gupa V, Ali H, et al. Updated results from a phase 1/2 clinical trial of tagraxofusp, A CD123-targeted therapy, in patients with poor-risk myelofibrosis. Oral presentation #S218. 25th EHA Annual Congress; Jun 12, 2020; Virtual.
  2. U.S. Food and Drug Administration. FDA approves tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm. Published Dec 26, 2018. Accessed Aug 17, 2020.