ELZONRIS Solution for injection Ref.[10205] Active ingredients: Tagraxofusp

Following administration of tagraxofusp-erzs 12 mcg/kg via 15-minute infusion in patients with BPDCN, the mean (SD) area under the plasma drug concentration over time curve (AUC) was 231 (123) hr·mcg/L and maximum plasma concentration (C_max) was 162 (58.1) mcg/L.

Distribution

Mean (SD) volume of distribution of tagraxofusp-erzs is 5.1 (1.9) L in patients with BPDCN.

Elimination

Mean (SD) clearance is 7.1 (7.2) L/hr in patients with BPDCN. Mean (SD) terminal half-life of tagraxofusp-erzs is 0.7 (0.3) hours.

Anti-Product Antibody Formation Affecting Pharmacokinetics

Pharmacokinetic data obtained following doses given in Cycle 3 showed increased titers of anti-drug antibodies and reduced free ELZONRIS concentration in most plasma samples. Following administration of tagraxofusp-erzs 12 mcg/kg via 15-minute infusion in patients with pre-existing anti-drug antibodies, the mean (SD) volume of distribution of tagraxofusp-erzs is 21.2 (25.4) L, clearance is 13.9 (19.4) L/hr, AUC is 151 (89.2) hr·mcg/L and C_max is 80.0 (82.2) mcg/L.

Specific Populations

No clinically significant differences in the pharmacokinetics of tagraxofusp-erzs were observed based on age (22 to 84 years), sex, mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m², estimated by MDRD), mild (total bilirubin ≤ ULN and AST >ULN, or total bilirubin 1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment or body weight after adjusting dose by body weight. The effect of severe renal impairment (eGFR 15 to 29 mL/min/1.73 m²), or severe hepatic impairment (total bilirubin >3 times ULN and any AST) on tagraxofusp-erzs pharmacokinetics is unknown.

Drug Interaction Studies

No drug-drug interaction studies have been conducted with ELZONRIS.

No studies have been conducted to assess the carcinogenic or genotoxic potential of tagraxofusp. Animal fertility studies have not been conducted with tagraxofusp-erzs.

At human equivalent doses greater than or equal to 1.6 times the recommended dose based on body surface area, severe kidney tubular degeneration/necrosis was observed in cynomolgus monkeys. At human equivalent doses equal to the recommended dose, degeneration/necrosis of the choroid plexus in the brain was observed in cynomolgus monkeys. The reversibility of this finding was not assessed at lower doses, but the finding was irreversible and became progressively more severe at a human equivalent dose 1.6 times the recommended dose, 3 weeks after dosing stopped.

14.1 First-Line Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

STML-401-0114 (NCT 02113982; Study 0114) was a multicenter, open-label, single-arm, clinical trial that included a prospective cohort of 13 patients with treatment-naive BPDCN. Treatment consisted of ELZONRIS 12 mcg/kg intravenously over 15 minutes once daily on days 1 to 5 of a 21-day cycle. Patient baseline characteristics are presented in Table 5.

Table 5. Baseline Demographics of Patients with Treatment-Naive BPDCN:

The efficacy of ELZONRIS in patients with treatment-naive BPDCN was based on the rate of complete response or clinical complete response (CR/CRc). Key efficacy measures are presented in Table 6. The median time to CR/CRc was 57 days (range: 14 to 107).

Table 6. Efficacy Measures in Patients with Treatment-Naive BPDCN:

* CRc is defined as complete response with residual skin abnormality not indicative of active disease.

14.2 Relapsed or Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

STML-401-0114 (NCT02113982; Study 0114) was a multicenter, open-label, single-arm, clinical trial that included 15 patients with relapsed or refractory BPDCN. Treatment consisted of ELZONRIS 12 mcg/kg on days 1 to 5 of each 21-day cycle. Patient baseline characteristics are presented in Table 7.

Table 7. Baseline Demographics of Patients with Relapsed or Refractory BPDCN:

In the 15 patients with relapsed/refractory BPDCN, one patient achieved a CR (duration: 111 days) and one patient achieved a CRc (duration: 424 days).