cokinetics 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 byMDRD), mild (total bilirubin ≤ ULN and AST >ULN, or total bilirubin 1 to 1.5 times ULN and any AST) ormoderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment or body weight after adjustingdose by body weight. The effect of severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2), or severe hepaticimpairment (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.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No studies have been conducted to assess the carcinogenic or genotoxic potential of tagraxofusp. Animalfertility studies have not been conducted with tagraxofusp-erzs.
13.2 Animal Toxicology and/or Pharmacology
At human equivalent doses greater than or equal to 1.6 times the recommended dose based on body surfacearea, severe kidney tubular degeneration/necrosis was observed in cynomolgus monkeys. At human equivalentdoses 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 wasirreversible and became progressively more severe at a human equivalent dose 1.6 times the recommendeddose, 3 weeks after dosing stopped.
14 CLINICAL STUDIES
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 thatincluded a prospective cohort of 13 patients with treatment-naive BPDCN.
Treatment consisted of ELZONRIS12 mcg/kg intravenously over 15 minutes once daily on days 1 to 5 of a 21-day cycle. Patient baselinecharacteristics are presented in Table 5.
Table 5. Baseline Demographics of Patients with Treatment-Naive BPDCN
Parameter N=13
Gender, N (%)
Male
Female
11 (84.6)
2 (15.4)
Age (years), N (%)
Median
Minimum, Maximum
65.0
22, 84
ECOG, N (%)
0
1
8 (61.5)
5 (38.5)
BPDCN at Baseline, N (%)
Skin
Bone Marrow
Peripheral Blood
Lymph Nodes
Viscera
13 (100.0)
7 (53.8)
3 (23.1)
6 (46.2)
2 (15.4)
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
Parameter N=13
CR/CRc* Rate, N (%)
(95% CI)
7 (53.8)
(25.1, 80.8)
Duration of CR/CRc (months)
Median
Minimum, Maximum
Not Reached
3.9, 12.2
Duration of follow up (months)
Median
Minimum, Maximum
11.5
0.2, 12.7
* 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 thatincluded 15 patients with relapsed or refractory BPDCN. Treatment consisted of ELZONRIS 12 mcg/kg ondays 1 to 5 of each 21-day cycle. Patient baseline characteristics are presented in Table 7.
Table 7. Baseline Demographics of Pat |
