RESULTS OF PIVOTAL PHASE 2 CLINICAL TRIAL OF TAGRAXOFUSP (SL-401) IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)
Author(s): ,
Naveen Pemmaraju
Affiliations:
MD Anderson Cancer Center,Houston,United States
,
Andrew Lane
Affiliations:
Dana Farber Cancer Institute,Boston,United States
,
Kendra Sweet
Affiliations:
H. Lee Moffitt Cancer Center,Tampa,United States
,
Anthony Stein
Affiliations:
City of Hope National Medical Center,Duarte,United States
,
Sumithira Vasu
Affiliations:
The Ohio State University,Columbus,United States
,
David Rizzieri
Affiliations:
Duke University Medical Center,Durham,United States
,
Eunice Wang
Affiliations:
Roswell Park Cancer Institute,Buffalo,United States
,
Madeleine Duvic
Affiliations:
MD Anderson Cancer Center,Houston,United States
,
Sharon Spence
Affiliations:
Stemline Therapeutics,New York,United States
,
Shay Shemesh
Affiliations:
Stemline Therapeutics,New York,United States
,
Christopher Brooks
Affiliations:
Stemline Therapeutics,New York,United States
,
Ivan Bergstein
Affiliations:
Stemline Therapeutics,New York,United States
,
Janice Chen
Affiliations:
Stemline Therapeutics,New York,United States
,
Peter McDonald
Affiliations:
Stemline Therapeutics,New York,United States
,
J. Mark Sloan
Affiliations:
Boston University School of Medicine,Boston,United States
,
Todd Rosenblat
Affiliations:
Columbia University Medical Center,New York,United States
,
Oleg Akilov
Affiliations:
University of Pittsburgh Medical Center,Pittsburgh,United States
,
Jeffrey Lancet
Affiliations:
H. Lee Moffitt Cancer Center,Tampa,United States
,
Hagop Kantarjian
Affiliations:
MD Anderson Cancer Center,Houston,United States
Marina Konopleva
Affiliations:
MD Anderson Cancer Center,Houston,United States
EHA Library. Pemmaraju N. Jun 15, 2019; 266680; PS1063
Dr. Naveen Pemmaraju
Dr. Naveen Pemmaraju
Contributions
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Abstract

Abstract: PS1063

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with historical overall survival (OS) of 8-14 months from diagnosis. Tagraxofusp is a targeted therapy directed to CD123, a target highly expressed on BPDCN. The pivotal trial results presented here provided the basis for FDA approval of tagraxofusp for the treatment of BPDCN in adult and pediatric patients 2 years or older, and a marketing authorization application (MAA) is under review.

Aims
Determine the recommended dose, safety and efficacy of tagraxofusp in patients with BPDCN.

Methods
This multicenter, multi-stage, open label, single-arm pivotal trial enrolled patients with treatment-naive or previously-treated BPDCN. In Stage 1 (dose escalation) patients received tagraxofusp daily IV infusions at 7, 9, or 12 mcg/kg on days 1-5 of a 21-day cycle. In Stage 2 (expansion) and Stage 3 (pivotal, confirmatory), patients received tagraxofusp at 12 mcg/kg. Key efficacy measures included objective response rate (ORR), complete response (CR), clinical CR (CRc, defined as CR with residual skin abnormality not indicative of active disease), and overall survival (OS). Patients were enrolled in 7 US sites.

Results
44 patients with BPDCN (29 treatment-naive and 15 previously-treated) were included in the analysis. Median age was 69 years (range, 22-84) and 82% were male. Baseline sites of disease: skin (93%), bone marrow (52%), lymph nodes (48%), peripheral blood and viscera (18%). Safety data were derived from a pooled analysis of 94 patients with myeloid malignancies treated with 12 mcg/kg of tagraxofusp. Most common adverse reactions (N=94; incidence ≥ 30%) were capillary leak syndrome (CLS), nausea, fatigue, peripheral edema, pyrexia, and weight increase. Most common laboratory abnormalities (incidence ≥ 50%) were decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, alanine aminotransferase and aspartate aminotransferase. CLS, defined as any event reported as CLS or the occurrence of at least 2 of the following within 7 days of each other: hypoalbuminemia, edema, or hypotension was 46% grades 1 or 2; 6% grade 3; 1% grade 4; and 2% grade 5. In treatment-naive patients (n=29), ORR was 90%, CR+CRc rate was 72%, and 45% were bridged to stem cell transplant (SCT) (10 allo+3 auto). Median OS was not yet reached at the time of the analysis (median follow-up 23.0 mos, (range 0.2-41 mos). The Stage 3 cohort met the prespecified primary endpoint with a 54% (7/13) rate of CR+CRc (95% CI: 25.1, 80.8). In previously-treated patients, ORR was 67% (10/15), including 1 CR and 1 CRc (subsequently bridged to SCT).

Conclusion
This clinical trial was the largest prospectively designed trial dedicated to patients with BPDCN. The study demonstrated high response rates that were generally achieved early in the course of treatment and maintained over multiple cycles of therapy. The safety profile of tagraxofusp was predictable and manageable. CLS was identified as the most serious TRAE and the tagraxofusp prescribing information includes management guidelines that were developed and implemented during the trial. Tagraxofusp is approved in the US for the treatment of BPDCN and a MAA is under review in the EU. 

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Clinical data

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