PS1063 RESULTS OF PIVOTAL PHASE 2 CLINICAL TRIAL OF TAGRAXOFUSP (SL‐401) IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)
Authors: N. Pemmaraju, A. Lane, K. Sweet, A. Stein, S. Vasu, D. Rizzieri, E. Wang, M. Duvic, S. Spence, S. Shemesh, C. Brooks, I. Bergstein, J. Chen, P. McDonald, J.M. Sloan, T. Rosenblat, O. Akilov, J. Lancet, H. Kantarjian, M. Konopleva
Journal: HemaSphere (2019)

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). Summary/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.