批准日期：2018年12月21日 公司：Stemline Therapeutics, Inc.
最常见的实验室异常decreasesin白蛋白(发生率≥50%),血小板、血红蛋白,钙,钠,并增加inglucose、ALT和AST。如需报告疑似不良反应，请致电StemlineTherapeutics, Inc.(电话877-332-7961)或FDA(电话1- 800-fdaa-1088或www.fda.gov/medwatch)。
ELZONRIS (tagraxofusp-erzs)注射液是一种无防腐剂、无菌、透明、无色、1mLsolution中1000mcg的注射液，装在单剂量玻璃瓶中。每个纸盒包含一个小瓶(NDC 72187-0401-1)。
储存在冰箱在-25°C和-15°C (-13°F和5°F)。保护ELZONRIS从光存储在原来的包装，直到使用的时间。在室温下解冻瓶15°C和25°C之间(59°F (77°F)在准备之前[参见管理准备(2.3)]。小瓶解冻后不要再冷冻。容器过期后请勿使用。
FDA Approves ELZONRIS(tagraxofusp), the First Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm and First CD123-Targeted Therapy
U.S. Food and Drug Administration (FDA) has granted approval of ELZONRIS™ (tagraxofusp-erzs; SL-401) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and pediatric patients two years and older, in both treatment-naïve and previously-treated populations. ELZONRIS is the first treatment approved for BPDCN and the first approved CD123-targeted therapy.
ELZONRIS Clinical Trial Design
The ELZONRIS BPDCN clinical trial was the largest prospective trial ever conducted in this disease. This multicenter, multi-cohort, open-label, single-arm, clinical trial (STML-401-0114; NCT 02113982) enrolled 47 patients with BPDCN, including 32 treatment-naïve and 15 previously-treated patients, at seven sites in the U.S. Patients received ELZONRIS intravenously on days 1-5 of a 21-day cycle for multiple consecutive cycles. The trial consisted of three stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion) and Stage 3 (pivotal, confirmatory). Patients were also enrolled in an additional cohort (Stage 4) to enable uninterrupted access to ELZONRIS.
ELZONRIS Efficacy and Safety
Approval was based on a multicenter, multicohort, open-label, single-arm clinical trial (STML-401-0114; NCT 02113982) in patients with treatment-naïve or previously-treated BPDCN. In the Stage 3 (pivotal) cohort, 13 patients with treatment-naïve BPDCN received ELZONRIS at the labeled dose and schedule. Efficacy was based on the rate of complete response or clinical complete response (CR/CRc), with CRc defined as complete response with residual skin abnormality not indicative of active disease. In this pivotal cohort, the CR/CRc rate was 53.8 percent (7/13) (95% CI: 25.1, 80.8). The median duration of CR/CRc was not reached (range: 3.9 to 12.2 months).
The safety of ELZONRIS was assessed in 94 adults with treatment-naïve or previously-treated myeloid malignancies treated with ELZONRIS at the labeled dose and schedule. The most common adverse reactions (incidence ≥30%) were capillary leak syndrome (CLS), nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥50%) were decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
ELZONRIS Overall Clinical Program in BPDCN
Clinical data from Study STML-401-0114 (NCT 02113982) were presented at the American Society of Hematology (ASH) annual meeting earlier this month. In 29 treatment-naïve patients who received ELZONRIS at 12 mcg/kg/day, the overall response rate (ORR) was 90 percent (26/29) (95% CI: 72.6, 97.8). In these patients, the CR/CRc rate was 72 percent (21/29) (95% CI: 52.8, 87.3) with a median duration of CR/CRc not reached (range: 1.3 to 32.2 months). Forty-five percent (13/29) of these patients were bridged to stem cell transplant (SCT), following remission on ELZONRIS.
The median overall survival (OS), among 29 treatment-naïve patients who received ELZONRIS at 12 mcg/kg/day was not reached (range: 0.2 to 42.0 months, with median follow-up of 23.0 months [range: 0.2 to 41+ months]).
ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older.
The ELZONRIS label contains a boxed warning for CLS, which may be life-threatening or fatal and can occur in patients receiving ELZONRIS. Physicians are advised to monitor for signs and symptoms of CLS and take actions as recommended in the full prescribing information.
WARNINGS AND PRECAUTIONS
Capillary Leak Syndrome
ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension.
Capillary leak syndrome is defined as any event reported as CLS during treatment with ELZONRIS or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure <90 mmHg).
Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥3.2 g/dL.
During treatment with ELZONRIS, ensure that serum albumin levels are ≥3.5 g/dL and have not been reduced by ≥0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability.
Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time.