RESULTS FROM ONGOING PHASE 1/2 CLINICAL TRIAL OF TAGRAXOFUSP (SL-401) IN PATIENTS WITH INTERMEDIATE, OR HIGH RISK, RELAPSED/REFRACTORY MYELOFIBROSIS
Author(s): ,
Naveen Pemmaraju
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Haris Ali
Affiliations:
City of Hope,Duarte,United States
,
Vikas Gupta
Affiliations:
Princess Margaret Cancer Centre,Toronto,Canada
,
Abdulraheem Yacoub
Affiliations:
Kansas University Cancer Center,Kansas City,United States
,
Gary Schiller
Affiliations:
David Geffen School of Medicine at UCLA,Los Angeles,United States
,
Sangmin Lee
Affiliations:
Weill Cornell Medical Center,New York,United States
,
Moshe Talpaz
Affiliations:
University of Michigan Health System,Ann Arbor,United States
,
Eunice Wang
Affiliations:
Roswell Park Comprehensive Cancer Center,Buffalo,United States
,
Minakshi Taparia
Affiliations:
University of Alberta Hospital,Edmonton,Canada
,
Megan Sardone
Affiliations:
Stemline Therapeutics,New York,United States
,
Halyna Wysowskyj
Affiliations:
Stemline Therapeutics,New York,United States
,
Shay Shemesh
Affiliations:
Stemline Therapeutics,New York,United States
,
Janice Chen
Affiliations:
Stemline Therapeutics,New York,United States
,
Chris Brooks
Affiliations:
Stemline Therapeutics,New York,United States
,
Enrique Poradosu
Affiliations:
Stemline Therapeutics,New York,United States
,
Peter McDonald
Affiliations:
Stemline Therapeutics,New York,United States
,
Nicole Rupprecht
Affiliations:
Stemline Therapeutics,New York,United States
,
Animesh Pardanani
Affiliations:
Mayo Clinic,Rochester,United States
,
Ayalew Tefferi
Affiliations:
Mayo Clinic,Rochester,United States
,
Srdan Verstovsek
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Joseph Khoury
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
Mrinal Patnaik
Affiliations:
Mayo Clinic,Rochester,United States
EHA Library. Pemmaraju N. 06/14/19; 266467; PF668
Dr. Naveen Pemmaraju
Dr. Naveen Pemmaraju
Contributions
Abstract

Abstract: PF668

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Patients with myelofibrosis (MF) who fail or are intolerant to JAK inhibitors (JAKi) have limited treatment options. Tagraxofusp is a targeted therapy directed to CD123 that was approved by the US FDA for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). CD123 is expressed on a variety of malignancies including BPDCN, acute myeloid leukemia (AML), and certain myeloproliferative neoplasms (MPN), including MF. Moreover, CD123plasmacytoid dendritic cells (pDCs), the cell of origin of BPDCN, have been detected in the microenvironment of certain myeloid neoplasms, including MF, where they may play a tumor-promoting role.1,2,3 Notably, pDCs share a common precursor cell with monocytes, and monocytosis has been reported as a poor prognostic factor, associated with rapid disease progression and shortened survival, suggesting an accelerated disease phase in MF.As such, tagraxofusp may offer a novel and rational therapeutic approach in patients with relapsed/refractory MF, including patients with monocytosis. 

Aims
Primary objectives include assessment of safety, determining the recommended Phase 2 dose (RP2D) and schedule, and evaluating efficacy in patients with MF who were relapsed, refractory, or unable to tolerate JAKi.

Methods
This multicenter, open-label Phase 1/2 trial is enrolling patients with MF. In the Stage 1 (dose escalation), tagraxofusp was administered as a daily IV infusion at 7, 9, and 12 mcg/kg on days 1-3 every 21 days (cycle 1-4), 28 days (cycles 5-7), and 42 days (cycles 8+). In Stage 2 (expansion), patients are receiving the RP2D (12 mcg/kg).

Results
23 patients with MF received tagraxofusp, including 12 patients who received ≥ 3 prior lines of therapy. Median age 69 years (range 55-81), 61% were female, and 30% had baseline monocytosis (≥ 1x109/L). Baseline risk assessment based on the DIPSS Plus risk group assessment showed 1 patient (4%) with intermediate-1, 12 patients (52%) with intermediate-2, and 10 patients (44%) with high-risk. At study entry, the median platelet count was 59 K/uL with 71% of patients had baseline platelets <100 K/uL, of which 8 patients had platelets <50 K/uL. 87% of patients had baseline splenomegaly (spleen palpable ≥ 5 cm below the left costal margin [LCM]). Most common treatment-related adverse events (TRAEs, incidence ≥ 15%) include headache, hypoalbuminemia, alanine aminotransferase increased and thrombocytopenia. The most common ≥ grade 3 TRAE was thrombocytopenia (8%). Capillary leak syndrome was reported in 1 patient (grade 3). Among the 14 evaluable patients with baseline splenomegaly, 57% had spleen size reductions: 43% (6/14) had reductions of > 25%, of which 3 patients had reductions of ≥ 45%. In 5 patients with baseline splenomegaly and monocytosis, 80% (4/5) had reductions of > 25%, of which 2 had reductions of ≥ 45%. Six patients, including 3 patients with monocytosis and 5 patients with platelets <100 K/uL, had treatment duration of 6 months or more.

Conclusion
Tagraxofusp demonstrated single agent activity, with a predictable and manageable safety profile, in patients with relapsed/refractory MF, including in patients with monocytosis, a poor prognostic factor, both constituting potential areas of unmet medical need. Enrollment continues, and updated trial data will be presented. Registrational trial designs are being evaluated. Trial information: NCT02268253.

 

1Patnaik, Haematologica 2019; 2Lai, Blood Adv. 2019; 3Veletic, Blood 2019; 4Tefferi, Br J Haematol 2018.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Clinical trial, Myelofibrosis, Myeloproliferative disorder, Targeted therapy

Abstract: PF668

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Patients with myelofibrosis (MF) who fail or are intolerant to JAK inhibitors (JAKi) have limited treatment options. Tagraxofusp is a targeted therapy directed to CD123 that was approved by the US FDA for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). CD123 is expressed on a variety of malignancies including BPDCN, acute myeloid leukemia (AML), and certain myeloproliferative neoplasms (MPN), including MF. Moreover, CD123plasmacytoid dendritic cells (pDCs), the cell of origin of BPDCN, have been detected in the microenvironment of certain myeloid neoplasms, including MF, where they may play a tumor-promoting role.1,2,3 Notably, pDCs share a common precursor cell with monocytes, and monocytosis has been reported as a poor prognostic factor, associated with rapid disease progression and shortened survival, suggesting an accelerated disease phase in MF.As such, tagraxofusp may offer a novel and rational therapeutic approach in patients with relapsed/refractory MF, including patients with monocytosis. 

Aims
Primary objectives include assessment of safety, determining the recommended Phase 2 dose (RP2D) and schedule, and evaluating efficacy in patients with MF who were relapsed, refractory, or unable to tolerate JAKi.

Methods
This multicenter, open-label Phase 1/2 trial is enrolling patients with MF. In the Stage 1 (dose escalation), tagraxofusp was administered as a daily IV infusion at 7, 9, and 12 mcg/kg on days 1-3 every 21 days (cycle 1-4), 28 days (cycles 5-7), and 42 days (cycles 8+). In Stage 2 (expansion), patients are receiving the RP2D (12 mcg/kg).

Results
23 patients with MF received tagraxofusp, including 12 patients who received ≥ 3 prior lines of therapy. Median age 69 years (range 55-81), 61% were female, and 30% had baseline monocytosis (≥ 1x109/L). Baseline risk assessment based on the DIPSS Plus risk group assessment showed 1 patient (4%) with intermediate-1, 12 patients (52%) with intermediate-2, and 10 patients (44%) with high-risk. At study entry, the median platelet count was 59 K/uL with 71% of patients had baseline platelets <100 K/uL, of which 8 patients had platelets <50 K/uL. 87% of patients had baseline splenomegaly (spleen palpable ≥ 5 cm below the left costal margin [LCM]). Most common treatment-related adverse events (TRAEs, incidence ≥ 15%) include headache, hypoalbuminemia, alanine aminotransferase increased and thrombocytopenia. The most common ≥ grade 3 TRAE was thrombocytopenia (8%). Capillary leak syndrome was reported in 1 patient (grade 3). Among the 14 evaluable patients with baseline splenomegaly, 57% had spleen size reductions: 43% (6/14) had reductions of > 25%, of which 3 patients had reductions of ≥ 45%. In 5 patients with baseline splenomegaly and monocytosis, 80% (4/5) had reductions of > 25%, of which 2 had reductions of ≥ 45%. Six patients, including 3 patients with monocytosis and 5 patients with platelets <100 K/uL, had treatment duration of 6 months or more.

Conclusion
Tagraxofusp demonstrated single agent activity, with a predictable and manageable safety profile, in patients with relapsed/refractory MF, including in patients with monocytosis, a poor prognostic factor, both constituting potential areas of unmet medical need. Enrollment continues, and updated trial data will be presented. Registrational trial designs are being evaluated. Trial information: NCT02268253.

 

1Patnaik, Haematologica 2019; 2Lai, Blood Adv. 2019; 3Veletic, Blood 2019; 4Tefferi, Br J Haematol 2018.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Clinical trial, Myelofibrosis, Myeloproliferative disorder, Targeted therapy

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