RESULTS FROM ONGOING PHASE 1/2 CLINICAL TRIAL OF TAGRAXOFUSP (SL-401) IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
Author(s): ,
Mrinal Patnaik
Affiliations:
Mayo Clinic,Rochester,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
Naveen Pemmaraju
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. Patnaik M. 06/14/19; 266471; PF672
Mrinal Patnaik
Mrinal Patnaik
Contributions
Abstract

Abstract: PF672

Type: Poster Presentation

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

Location: Poster area

Background
Patients with chronic myelomonocytic leukemia (CMML) have historically poor outcomes, with ~6-7 month median overall survival (OS) in the relapsed/refractory (r/r) setting. Splenomegaly is a major cause of morbidity, is a poor prognostic factor and has emerged as a potential therapeutic target in CMML. Tagraxofusp (SL-401) is a targeted therapy directed to CD123, a target expressed on CMML blasts, monocytes and neoplastic microenvironmental plasmacytoid dendritic cells (pDCs) that are part of the CMML malignant clone, as well as on a variety of additional malignancies. Tagraxofusp was approved by the US FDA for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) and is being investigated in other CD123-expressing malignancies. 

Aims
Primary objectives include assessment of safety, determining the recommended Phase 2 dose (RP2D) and schedule, and evaluating efficacy in patients with CMML.

Methods
This multicenter, open-label, Phase 1/2 clinical trial is enrolling patients with CMML. In 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), every 28 days (cycles 5-7), and every 42 days (cycles 8 and beyond). In Stage 2 (expansion), patients receive the RP2D (12 mcg/kg).

Results
20 patients with CMML (CMML-1 [n=12]; CMML-2 [n=8]) were treated with tagraxofusp, including 18 in the relapsed/refractory setting, with hypomethylating agents (HMAs) being the most commonly administered prior therapy. Median age was 69 years (range 43-80) and 80% were male. 10 patients (50%) had baseline splenomegaly (defined as spleen palpable below the left costal margin [BCM]), of which 6 had baseline splenomegaly ≥ 5 cm BCM. Most common treatment-related adverse events (TRAEs, incidence ≥ 20%) were hypoalbuminaemia, thrombocytopenia, nausea, vomiting and fatigue. Most common ≥ grade 3 TRAEs were thrombocytopenia (35%) and nausea (5%). Capillary leak syndrome was reported in 3 patients (grade 1-2). 100% (10/10) of patients with baseline splenomegaly had a spleen response by physical exam: 80% (8/10) had spleen size reduction of ≥ 50% and 67% (4/6) with baseline spleen size ≥ 5 cm had spleen size reduction of ≥ 50%. Three patients treated with tagraxofusp achieved bone marrow complete responses (BMCRs), including 1 patient who was bridged to stem cell transplant in remission on tagraxofusp. 

Conclusion
Tagraxofusp demonstrated single agent activity in patients with CMML and splenomegaly, an area of potential unmet medical need. Given the expression of CD123 in CMML, tagraxofusp represents a rational therapeutic approach in this disease. Updated data will be presented, and a registrational trial is planned. Trial information: NCT02268253.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Chronic myelomonocytic leukemia, Clinical trial, Myeloproliferative disorder, Targeted therapy

Abstract: PF672

Type: Poster Presentation

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

Location: Poster area

Background
Patients with chronic myelomonocytic leukemia (CMML) have historically poor outcomes, with ~6-7 month median overall survival (OS) in the relapsed/refractory (r/r) setting. Splenomegaly is a major cause of morbidity, is a poor prognostic factor and has emerged as a potential therapeutic target in CMML. Tagraxofusp (SL-401) is a targeted therapy directed to CD123, a target expressed on CMML blasts, monocytes and neoplastic microenvironmental plasmacytoid dendritic cells (pDCs) that are part of the CMML malignant clone, as well as on a variety of additional malignancies. Tagraxofusp was approved by the US FDA for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) and is being investigated in other CD123-expressing malignancies. 

Aims
Primary objectives include assessment of safety, determining the recommended Phase 2 dose (RP2D) and schedule, and evaluating efficacy in patients with CMML.

Methods
This multicenter, open-label, Phase 1/2 clinical trial is enrolling patients with CMML. In 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), every 28 days (cycles 5-7), and every 42 days (cycles 8 and beyond). In Stage 2 (expansion), patients receive the RP2D (12 mcg/kg).

Results
20 patients with CMML (CMML-1 [n=12]; CMML-2 [n=8]) were treated with tagraxofusp, including 18 in the relapsed/refractory setting, with hypomethylating agents (HMAs) being the most commonly administered prior therapy. Median age was 69 years (range 43-80) and 80% were male. 10 patients (50%) had baseline splenomegaly (defined as spleen palpable below the left costal margin [BCM]), of which 6 had baseline splenomegaly ≥ 5 cm BCM. Most common treatment-related adverse events (TRAEs, incidence ≥ 20%) were hypoalbuminaemia, thrombocytopenia, nausea, vomiting and fatigue. Most common ≥ grade 3 TRAEs were thrombocytopenia (35%) and nausea (5%). Capillary leak syndrome was reported in 3 patients (grade 1-2). 100% (10/10) of patients with baseline splenomegaly had a spleen response by physical exam: 80% (8/10) had spleen size reduction of ≥ 50% and 67% (4/6) with baseline spleen size ≥ 5 cm had spleen size reduction of ≥ 50%. Three patients treated with tagraxofusp achieved bone marrow complete responses (BMCRs), including 1 patient who was bridged to stem cell transplant in remission on tagraxofusp. 

Conclusion
Tagraxofusp demonstrated single agent activity in patients with CMML and splenomegaly, an area of potential unmet medical need. Given the expression of CD123 in CMML, tagraxofusp represents a rational therapeutic approach in this disease. Updated data will be presented, and a registrational trial is planned. Trial information: NCT02268253.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Chronic myelomonocytic leukemia, Clinical trial, Myeloproliferative disorder, Targeted therapy

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