温馨提醒：本说明书仅供参考，最新的说明书详见药品附带的说明书。

1适应症和用途

POTELIGEO适用于在至少一种先前的全身性治疗后用于治疗复发性或难治性真菌病（MF）或塞氏病（SS）的成年患者。

2剂量和给药

2.1推荐剂量

POTELIGEO的推荐剂量为至少60分钟静脉输注1 mg / kg。在第一个28天周期的第1、8、15和22天给药，然后在每个随后的28天周期的第1和15天给药，直至疾病进展或出现不可接受的毒性。

在预定剂量的2天内管理POTELIGEO。如果错过剂量，请尽快给予下一个剂量，并恢复给药时间表。

请勿皮下或快速静脉内施用POTELIGEO。

推荐用药

首次POTELIGEO输注时，应先用苯海拉明和对乙酰氨基酚进行用药。

2.2毒性剂量调整

皮肤毒性

• 永久终止POTELIGEO以致威胁生命的皮疹（4级）或任何史蒂文斯－约翰逊综合症（SJS）或中毒性表皮坏死症（TEN）[ 参见警告和注意事项（5.1） ]。如果怀疑有SJS或TEN，则停止POTELIGEO，除非排除SJS或TEN并且皮肤反应已降至1级或以下，否则不要恢复。
• 如果发生中度或重度（2或3级）皮疹，请中断POTELIGEO并给予至少2周的局部糖皮质激素治疗。如果皮疹改善至1级或以下，可以恢复POTELIGEO [ 参见警告和注意事项（5.1） ]。
• 如果出现轻度（1级）皮疹，请考虑局部使用皮质类固醇。

输液反应

• 永久终止POTELIGEO进行危及生命的（4级）输注反应[ 请参阅警告和注意事项（5.2） ]。
• 暂时中断POTELIGEO的输注，以进行轻度至重度（1至3级）输注反应并治疗症状。在症状缓解后重新开始输注时，请将输注率降低至少50％。如果反应再次发生且难以控制，请停止输液。[ 请参阅警告和注意事项（5.2） ]。
• 如果发生输注反应，则应在随后的POTELIGEO输注中使用药物治疗（如苯海拉明和对乙酰氨基酚）。

2.3准备和管理

制备

• 给药前目视检查药品溶液中是否有颗粒物和变色。POTELIGEO是透明至微乳白色的无色溶液。如果观察到浑浊，变色或颗粒，则丢弃小瓶。
• 根据患者体重计算准备输注溶液所需的POTELIGEO剂量（毫克/千克）和小瓶数量。
• 无菌地将所需量的POTELIGEO抽入注射器中，并转移到装有0.9％USP氯化钠注射液的静脉（IV）袋中。稀释溶液的最终浓度应在0.1 mg / mL至3.0 mg / mL之间。
• 轻轻颠倒混合稀释的溶液。不要摇晃。
• 丢弃小瓶中所有未使用的部分。

稀释后的溶液与聚氯乙烯（PVC）或聚烯烃（PO）输液袋兼容。

行政

• 通过包含无菌，低蛋白结合，0.22微米（或等效值）在线过滤器的静脉输液管，在至少60分钟内施用输注溶液。
• 请勿将POTELIGEO与其他药物混合使用。
• 请勿通过同一静脉内管线同时使用其他药物。

稀释液的储存

制备后，应立即注入POTELIGEO溶液，或从输注制备之日起在2°C至8°C（36°F至46°F）的冷藏条件下保存不超过4小时。

不要冻结。不要摇晃。

3剂型和强度

注射剂：在单剂量小瓶中为澄清至微乳白色无色溶液，为20 mg / 5 mL（4 mg / mL）。

4禁忌症

没有。

5警告和注意事项

5.1皮肤毒性

POTELIGEO的患者发生了致命和威胁生命的皮肤不良反应，包括史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死溶解（TEN）。皮疹（药疹）是与POTELIGEO相关的最常见的不良反应之一。在试验1中，接受POTELIGEO治疗的患者中有25％（80/319）患有药疹的不良反应，其中18％为严重（3级），其中82％为1级或2级。528 在临床试验中接受POTELIGEO治疗的患者，报告的3级皮肤不良反应为3.6％，4级皮肤不良反应为<1％，SJS为<1％。

药疹的发作是可变的，并且受影响的区域和外观也有所不同。在试验1中，中位发病时间为15周，其中25％的病例在31周后发生。据报道，更常见的表现包括丘疹或斑丘疹，苔藓样，海绵状或肉芽肿性皮炎和丝状疹子。其他表现包括鳞状斑块，脓疱疹，毛囊炎，非特异性皮炎和牛皮癣样皮炎。

在整个治疗过程中监视患者的皮疹。皮肤毒性的管理包括局部用糖皮质激素和POTELIGEO的中断或永久终止[ 参见剂量和用法（2.2） ]。考虑进行皮肤活检以帮助区分药物喷发与疾病进展。

对于SJS或TEN或任何威胁生命的（第4级）反应，请永久停用POTELIGEO。对于可能的SJS或TEN，请中断POTELIGEO并重新启动，除非排除SJS或TEN并且皮肤反应已分解为1级或更低。

5.2输注反应

有报道称接受POTELIGEO治疗的患者发生致命和危及生命的输液反应。在试验1中，接受POTELIGEO治疗的患者中有35％（112/319）发生了输液反应，其中8％是严重反应（3级）。大多数反应（约90％）发生在第一次输注期间或之后不久。随后的输注也可能发生输注反应。最常见的体征包括畏寒，恶心，发烧，心动过速，僵硬，头痛和呕吐。

在所有患者中首次输注POTELIGEO时应考虑使用处方药（如苯海拉明和对乙酰氨基酚）。尚不确定用药是否会降低这些反应的风险或严重性。在试验1中，有42％的未用药前患者和32％的有用药前患者发生了输液反应。密切监视患者输液反应的体征和症状，并中断输液以进行任何等级反应并及时治疗[ 请参阅剂量和用法（2.2） ]。

5.3感染

用POTELIGEO治疗的患者发生了致命和威胁生命的感染，包括败血症，肺炎和皮肤感染。在试验1中，随机分配给POTELIGEO的患者中有18％（34/184）患有3级或更高级别的感染或与感染相关的严重不良反应。监测患者感染的体征和症状并及时治疗。

5.4自身免疫并发症

在POTELIGEO的接受者中报告了致命的和威胁生命的免疫介导并发症。3级或更高级别的免疫介导的或可能由免疫介导的反应包括肌炎，心肌炎，多发性肌炎，肝炎，肺炎和吉兰-巴雷综合征的一种变异。据报道，在试验1中，1.9％（6/319）的POTELIGEO接受者使用全身免疫抑制剂进行免疫介导的反应，包括风湿性2级多肌痛患者。据报道1.3％的患者出现新的甲状腺功能减退症（1或2级），并通过观察或左甲状腺素治疗。根据怀疑的免疫介导的不良反应，适当中断或永久停用POTELIGEO。考虑POTELIGEO的收益/风险 有自身免疫病史的患者。

5.5 POTELIGEO后异基因造血干细胞移植（HSCT）的并发症

据报道，接受POTELIGEO后接受异基因HSCT的患者发生移植并发症的风险增加，包括严重（3级或4级）急性移植物抗宿主病（GVHD），类固醇难治性GVHD以及与移植相关的死亡。在移植前的收件人POTELIGEO，如果移植并发症的风险较高，有报道POTELIGEO是造血干细胞移植前较短的时间内（大约50天）内给出。密切关注患者，以获取移植相关并发症的早期证据。

6不良反应

标签的其他部分详细讨论了以下严重不良反应：

• 皮肤毒性[ 请参阅警告和注意事项（5.1） ]。
• 输液反应[ 请参阅警告和注意事项（5.2） ]。
• 感染[ 请参阅警告和注意事项（5.3） ]。
• 自身免疫并发症[ 见警告和注意事项（5.4） ]。
• POTELIGEO后同种异体HSCT的并发症[ 参见警告和注意事项（5.5） ]。

6.1临床试验经验

由于临床试验是在变化很大的条件下进行的，因此不能将在某种药物的临床试验中观察到的不良反应率直接与另一种药物的临床试验中观察到的不良反应率进行比较，并且可能无法反映实际中观察到的不良反应率。

试验1

以下描述的数据反映了在接受过至少一种先前系统治疗的成年MF或SS患者中，一项随机，开放标签，主动控制的临床试验中POTELIGEO的暴露情况[ 参见临床研究（14） ]。在370例接受治疗的患者中，随机给予184例（MF占57％，SS占43％）接受POTELIGEO随机治疗，186例（MF占53％，SS占47％）接受伏立诺他治疗。在伏立诺他臂，135名患者（73％）随后越过POTELIGEO总共319例治疗POTELIGEO。

在第28天的第1天，第8天，第15天和第22天以及随后的28天的第1天和第15天，在至少60分钟内以1 mg / kg的剂量静脉内施用POTELIGEO。处方药（苯海拉明，对乙酰氨基酚）是可选的，在首次输注时对65％的随机患者进行了处方。比较组每天口服一次伏立诺他400 mg，连续28天服用。继续治疗直至出现不可接受的毒性或进行性疾病。

中位年龄为64岁（范围为25至101岁），其中58％的患者为男性，70％为白人，99％的患者的东方合作肿瘤小组（ECOG）绩效状态为0或1。 3种先前的全身疗法。该试验要求中性粒细胞绝对计数（ANC）≥1500/ µL（如果涉及骨髓则≥1000 / µL），血小板计数≥100,000/ µL（如果涉及骨髓则≥75,000/ µL），肌酐清除率> 50 mL /分钟或血清肌酐≤1.5mg / dL，肝转氨酶≤正常上限（ULN）的2.5倍（如果淋巴瘤肝浸润，≤5倍正常值）。排除患有活动性自身免疫疾病，活动性感染，90天内的自体HSCT或先前的同种异体HSCT的患者。

在随机治疗期间，暴露于POTELIGEO的中位时间为5.6个月，其中48％（89/184）的患者接受了至少6个月的暴露，23％（43/184）的患者接受了至少12个月的暴露。伏立诺他的中位暴露时间为2.8个月，其中22％（41/186）的患者至少暴露6个月。

接受POTELIGEO随机或交叉治疗的患者中，在末次给药后90天内发生致命不良反应的发生率为2.2％（7/319）。

据报道，随机分配给POTELIGEO的患者中有36％（66/184）发生严重不良反应，最常见的是感染（16％的患者； 30/184）。在随机分配至POTELIGEO的患者中，> 2％的严重不良反应为肺炎（5％），败血症（4％），发热（4％）和皮肤感染（3％）；其他严重不良反应，每例2％的患者报告，包括肝炎，肺炎，皮疹，与输液有关的反应，下呼吸道感染和肾功能不全。在随机分组的患者中，有18％的患者因不良反应而停用POTELIGEO，最常见的原因是皮疹或药疹（7.1％）。

常见不良反应

最常见的不良反应（据报道≥20％的患者随机分配给POTELIGEO）为皮疹（包括药疹），输液相关的反应，疲劳，腹泻，上呼吸道感染和肌肉骨骼疼痛。其他常见的不良反应（据报道≥10％的患者随机分配至POTELIGEO）包括皮肤感染，发热，恶心，水肿，血小板减少，头痛，便秘，粘膜炎，贫血，咳嗽和高血压。表1总结了在试验1中，POTELIGEO的常见不良反应发生率比伏立诺他高≥2％。

表1：常见的不良反应（≥10％）的≥2％，发病率较高的POTELIGEO臂

在≥10％，其他常见的不良反应POTELIGEO臂1 ，2

• 一般疾病：疲劳（31％），水肿（16％）
• 胃肠道疾病：腹泻（28％），恶心（16％），便秘（13％）
• 血液和淋巴系统疾病：血小板减少症（14％），贫血（12％）
• 神经系统疾病：头痛（14％）
• 血管疾病：高血压（10％）
• 呼吸系统疾病：咳嗽（11％）

不良反应在≥5％但<10％POTELIGEO臂1 ，2

• 感染：念珠菌病（9％），尿路感染（9％），毛囊炎（8％），肺炎（6％），中耳炎（5％），疱疹病毒感染（5％）
• 研究：肾功能不全（9％），高血糖症（9％），高尿酸血症（8％），体重增加（8％），体重减轻（6％），低镁血症（6％）
• 精神疾病：失眠（9％），抑郁症（7％）
• 皮肤和皮下疾病：干燥症（8％），脱发症（7％）
• 神经系统疾病：头晕（8％），周围神经病变（7％）
• 代谢和营养失调：食欲下降（8％）
• 呼吸系统疾病：呼吸困难（7％）
• 一般疾病：发冷（7％）
• 胃肠道疾病：呕吐（7％），腹痛（5％）
• 伤害，中毒和手术并发症：下降（6％）
• 肌肉骨骼疾病：肌肉痉挛（5％）
• 心血管疾病：心律不齐（5％）
• 眼疾：结膜炎（5％）

选择其他不良反应1 ，2

• 肿瘤溶解综合征（<1％）
• 心肌缺血或梗塞（<1％）
• 心脏衰竭（<1％）

表2总结了POTELIGEO的常见治疗紧急实验室异常发生率比伏立诺他高≥2％。

表2：常用的新的或在与≥2％，发病率较高恶化实验室异常（≥10％）POTELIGEO臂

POTELIGEO组其他常见的治疗紧急实验室异常包括高血糖症（52％; 4％3-4级），贫血（35％; 2％3-4级），血小板减少症（29％，3-4级无），天冬氨酸转氨酶（AST）增加（25％; 2％3-4级），丙氨酸转氨酶（ALT）增加（18％; 1％3-4级），碱性磷酸酶增加（17％; 0％3-4级）和中性粒细胞减少症（10％； 2％3-4级）。在POTELIGEO臂的≥1％中观察到的4级治疗紧急实验室异常包括淋巴细胞减少症（5％），白细胞减少症（1％）和低磷血症（1％）。

1 包括分组术语

2 从184例患者随机分配至POTELIGEO

6.2免疫原性

与所有治疗性蛋白质一样，具有免疫原性的潜力。抗体形成的检测高度依赖于测定的灵敏度和特异性。另外，在测定中观察到的抗体（包括中和抗体）阳性的发生率可能受到多种因素的影响，包括测定方法，样品处理，样品收集的时间，伴随用药和潜在疾病。由于这些原因，将POTELIGEO抗体的发生率与其他研究或其他产品中抗体的发生率进行比较可能会产生误导。

在试验1 中用TELEGIGEO治疗的258例患者中，有10例（3.9％）通过电化学发光法检测到了治疗紧急（治疗诱导或治疗增强）的抗mogamulizumab-kpkc抗体阳性。没有阳性中和抗体反应。

6.3售后安全信息

在POTELIGEO的批准后使用过程中，确认了以下不良反应。由于这些反应是从不确定大小的人群中自愿报告的，因此并非总是能够可靠地估计其发生频率或建立与药物暴露的因果关系。

• 感染：乙型肝炎病毒激活
• 心脏疾病：应激性心肌病

8在特定人群中的使用

8.1怀孕

风险摘要

目前尚无孕妇使用POTELIGEO的数据可告知与药物相关的重大先天缺陷和流产风险。在一项动物生殖研究中，从器官发生开始到分娩开始，对怀孕的食蟹猕猴施用mogamulizumab-kpkc并未显示母体全身暴露于建议剂量下患者暴露量的27倍时的不良发育结果，基于AUC（参见数据）。通常，已知IgG分子会穿过胎盘屏障，并且在猴繁殖研究中，在胎儿血浆中检测到莫加单抗-kpkc。因此，POTELIGEO有潜力从母亲传播给发育中的胎儿。POTELIGEO 不建议在怀孕期间或有生育能力的女性不使用避孕药。

对于指定人群，主要出生缺陷和流产的估计背景风险尚不清楚。所有怀孕都有出生缺陷，流产或其他不良后果的背景风险。在美国普通人群中，临床公认的怀孕中主要先天缺陷和流产的估计背景风险分别为2-4％和15-20％。

数据

动物资料

从器官发生开始到分娩，每周一次接受静脉内施用mogamulizumab-kpkc的12只怀孕的食蟹猕猴，评估了mogamulizumab-kpkc对胚胎-胎儿发育的影响，暴露水平是临床剂量的27倍。Mogamulizumab-kpkc的给药并未显示出潜在的胚胎致死力，致畸性或胎儿发育迟缓，也未导致自然流产或胎儿死亡增加。用mogamulizumab-kpkc治疗的食蟹猴的存活胎儿（12只中有10只，对照组为12只中的11只）中，由于mogamulizumab-kpkc的药理活性导致表达CCR4的淋巴细胞减少；没有明显的mogamulizumab-kpkc相关的外部，内脏或骨骼异常。

8.2哺乳

风险摘要

没有关于母乳中POTELIGEO的存在，对母乳喂养的孩子的影响或对牛奶产量的影响的信息。应当考虑母乳喂养的发育和健康益处，以及母亲对POTELIGEO的临床需求以及POTELIGEO或潜在母体状况对母乳喂养孩子的任何潜在不利影响。

8.3生殖潜力的雌雄

不建议孕妇使用POTELIGEO或有生育能力的女性不使用避孕药具。

验孕

对于具有生殖潜力的女性，在启动POTELIGEO之前，请验证其怀孕状况。

避孕

建议具有生殖潜力的女性在接受POTELIGEO治疗期间以及最后一次服用POTELIGEO后至少3个月内使用有效的避孕方法。

8.4小儿使用

尚未确定POTELIGEO在儿科患者中的安全性和有效性。

8.5老年人使用

在试验1中接受POTELIGEO的 319例MF或SS患者中，有162岁（51％）≥65岁。在这些患者和年轻患者之间未观察到总体疗效差异。≥65岁的患者，发生不良反应的占35％，严重不良反应占36％；而65岁以下的患者，发生不良反应发生在3级以上，占36％，严重不良反应占29％。 。

11说明

Mogamulizumab-kpkc是一种重组人源化单克隆抗体，靶向表达CC趋化因子受体4（CCR4）的细胞。Mogamulizumab-kpkc是一种IgG1 kappa免疫球蛋白，其分子质量约为149 kDa。Mogamulizumab-kpkc是通过重组DNA技术在中国仓鼠卵巢细胞中产生的。

POTELIGEO（mogamulizumab-kpkc）注射剂是一种无菌，即用型，无防腐剂，澄清至微乳白色无色溶液，在单剂量小瓶中进行稀释，然后静脉内输注。每个小瓶在5 mL溶液中包含20 mg mogamulizumab-kpkc。每毫升溶液包含4 mg莫加莫珠单抗-kpkc，并配制为：一水柠檬酸（0.44 mg），甘氨酸（22.5 mg），聚山梨酯80（0.2 mg）和注射用水，USP。可能包含盐酸/氢氧化钠以将pH值调节至5.5。

12临床药理学

12.1行动机制

Mogamulizumab-kpkc是一种去岩藻糖基化的人源化IgG1 kappa单克隆抗体，与CCR4结合，CCR4是CC趋化因子的G蛋白偶联受体，参与淋巴细胞向各种器官的运输。非临床体外研究表明，mogamulizumab-kpkc结合可将细胞靶向抗体依赖性细胞毒性（ADCC），导致靶细胞耗竭。CCR4在某些T细胞恶性肿瘤的表面表达，并在调节性T细胞（Treg）和Th2 T细胞的一部分上表达。

12.2药效学

Mogamulizumab-kpkc暴露-反应关系和药效学反应的时间过程是未知的。

12.3药代动力学

在患有T细胞恶性肿瘤的患者中评估了Mogamulizumab-kpkc的药代动力学（PK）。除非另有说明，否则参数以几何平均值[％变异系数（％CV）]表示。在0.01到1.0 mg / kg的剂量范围内，Mogamulizumab-kpkc浓度随剂量成比例增加（批准的推荐剂量的0.01到1倍）。

重复服用批准的推荐剂量后，经过8次给药（12周）后达到稳态浓度，全身蓄积为1.6倍。在稳态下，峰浓度（C max，ss）为32（68％）µg / mL，谷浓度（C min，ss）为11（239％）µg / mL，而AUC ss为5577（125％） ）µg∙hr / mL。

分配

分配的中心体积为3.6 L（20％）。

消除

最终半衰期为17天（66％），清除率为12 mL / h（84％）。

特定人群：

根据年龄（范围：22至101岁），性别，种族，肾功能不全（肌酐清除率<90 mL / min，由Cockcroft-Gault估算），未观察到Mogamulizumab-kpkc PK的临床显着变化。胆红素≤ULN和AST 1.5至3倍ULN和任何AST）肝功能损害，疾病亚型（MF或SS），CCR4程度表达式或ECOG状态。尚不清楚严重肝功能损害（总胆红素> 3倍ULN和任何AST）对莫加米单抗-kpkc PK的影响。

药物相互作用研究

尚未与POTELIGEO进行药物相互作用研究。

13毒理学

13.1致癌，诱变和生育能力受损

POTELIGEO尚未进行致癌性或遗传毒性研究。

尚未进行任何具体研究来评估POTELIGEO对生育力的潜在影响。在长达26周的重复剂量毒理学研究中，在性成熟的猴子中未观察到雄性和雌性生殖器官中与mogamulizumab-kpkc相关的毒性作用。

14临床研究

试验1

一项随机，开放标签，多中心试验（研究0761-010； NCT01728805）评估了POTELIGEO在至少一项先前的全身治疗后对成年MF或SS患者的疗效。该试验将372名患者以1：1的比例随机分配至任一（186例； MF占56％，SS占44％）或伏立诺他（186例； MF占53％，SS占47％）。该试验包括不考虑肿瘤CCR4表达状态的患者，并排除了具有组织学转化，先前同种异体HSCT，90天内的自体HSCT，活动性自身免疫病或活动性感染的患者。该试验要求患者的ANC≥1500/ µL（如果涉及骨髓，则≥1000/ µL），血小板计数≥100,000/ µL（如果涉及骨髓，则≥75,000/ µL），肌酐清除率> 50 mL / min或血清肌酐≤1.5mg / dL，肝转氨酶≤ULN的2.5倍（如果淋巴瘤肝浸润，≤5倍ULN）。

在第一个28天周期的第1、8、15和22天以及每个后续周期的第1和15天至少60分钟内静脉内施用POTELIGEO的剂量为1 mg / kg。伏立诺他每天口服一次，剂量为400 mg，连续28天。继续治疗直至疾病进展或不可接受的毒性。经Vorinostat治疗且疾病进展或毒性不可接受的患者可以转到POTELIGEO。

中位年龄为64岁（范围：25至101），男性患者中58％，白人患者中70％。在研究基线时，38％患有IB-II期疾病，10％处于III期，52％处于IV期。先前全身治疗的中位数为3。在POTELIGEO小组中，有140例患者（75％）通过免疫组织化学获得了基线CCR4表达状态，其中所有患者在皮肤活检中≥1％的淋巴细胞中检测到CCR4，134 / 140例（96％）的CCR4检出率≥10％。在伏立诺他组中，CCR4表达状态相似。

在随机治疗期间，暴露于POTELIGEO的中位时间为5.6个月（范围：<1至45.3个月），其中48％的患者至少暴露6个月，23％的患者至少暴露12个月。伏立诺他的中位暴露时间为2.8个月（范围：<1至34.8个月），其中22％的患者至少暴露6个月。

疗效基于研究者评估的无进展生存期（PFS），该生存期定义为从随机分组之日起，到有记载的疾病或死亡进展为止的时间。其他功效指标包括基于整体综合反应标准的总体反应率（ORR），该标准综合了每个疾病区隔（皮肤，血液，淋巴结和内脏）的指标。应对措施需要在两次连续的疾病评估中得到确认，其中包括改良的严重度加权评估工具，皮肤照片，中央流式细胞仪和计算机断层扫描。

该试验表明，与伏立诺他相比，POTELIGEO显着延长了PFS（表3）。研究人员对PFS的Kaplan-Meier曲线如图1所示。在POTELIGEO组，对研究人员评估的PFS的估计中位随访时间为13个月，在伏立诺他组，为10.4个月。根据独立审查委员会的评估，在POTELIGEO组中，估计的PFS中位数为6.7个月（95％CI，5.6至9.4），在伏立诺他组中为3.8个月（95％CI，3.0至4.7）（危险比0.64； 95％CI） ：0.49，0.84）。

图1每个研究者的无进展生存期的Kaplan-Meier曲线

表3还总结了研究者评估的总体和病房确定的缓解率。该试验证明POTELIGEO可改善ORR 。

表3随机治疗的疗效（试验1）

16供应/存储和处理方式

POTELIGEO（mogamulizumab-kpkc）注射液是无菌，不含防腐剂，澄清至微乳白色无色溶液，装在纸箱中，纸箱中装有一个20 mg / 5 mL（4 mg / mL）单剂量玻璃小瓶（NDC 42747-761- 01）。

将小瓶在2°C至8°C（36°F至46°F）的冷藏条件下存放在原始包装中，以防止光照直至使用。不要冻结。不要摇晃。

17患者咨询信息

建议患者阅读FDA批准的患者标签（患者信息）。

告知患者以下不良反应的风险，可能需要进一步治疗和/或停用或停用POTELIGEO，包括：

• 皮肤毒性：建议患者就新的或恶化的皮疹立即联系他们的医护人员[ 请参阅警告和注意事项（5.1） ]。告知患者在接受POTELIGEO期间，皮疹随时可能发生。
• 输液反应：建议患者立即就输液反应的体征或症状与他们的医疗保健提供者联系[ 参见警告和注意事项（5.2） ]。
• 感染：建议患者就发热或其他感染证据联系其医疗保健提供者[ 请参阅警告和注意事项（5.3） ]。
• 自身免疫性并发症：建议患者将自身免疫性疾病的任何病史通知其医疗保健提供者[ 参见警告和注意事项（5.4） ]。
• POTELIGEO后同种异体HSCT的并发症：建议患者潜在的移植后并发症风险[ 见警告和注意事项（5.5） ]。
• 具生殖潜力的女性：建议在POTELIGEO治疗期间以及最后一次服用POTELIGEO后至少3个月内使用有效的避孕药[ 见在特定人群中使用（8.3） ]。

POTELIGEO ®（莫加木珠单抗-kpkc）
厂商：
协和麒麟公司
贝敏斯特，NJ 07921
US牌照号码2077

主要显示板-4 mg / mL瓶装纸箱

仅Rx

NDC 42747-761-01

POTELIGEO ®
（莫加木珠单抗-kpkc）

注射

20毫克/ 5毫升
（4毫克/毫升）

静脉输液

单剂量小瓶。
丢弃未使用的部分。

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。

本说明书来源于：美国FDA网站

https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/e53960ab-42a1-40d1-9c7d-eb013fe7f18f/spl-doc?hl=POTELIGEO

温馨提醒：

①建议您用 谷歌浏览器  在电脑上或手机  打开以上链接，就可以自动翻译成简体中文，而且翻译的还比较准确。

②本说明书仅供参考，最新的说明书详见药品附带的说明书。

1 INDICATIONS AND USAGE

POTELIGEO is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dose of POTELIGEO is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Administer on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of each subsequent 28-day cycle until disease progression or unacceptable toxicity.

Administer POTELIGEO within 2 days of the scheduled dose. If a dose is missed, administer the next dose as soon as possible and resume dosing schedule.

Do not administer POTELIGEO subcutaneously or by rapid intravenous administration.

Recommended Premedications

Administer premedication with diphenhydramine and acetaminophen for the first POTELIGEO infusion.

2.2 Dose Modifications for Toxicity

Dermatologic Toxicity

• Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) [see Warnings and Precautions (5.1)]. If SJS or TEN is suspected, stop POTELIGEO and do not resume unless SJS or TEN has been excluded and the cutaneous reaction has resolved to Grade 1 or less.
• If moderate or severe (Grades 2 or 3) rash occurs, interrupt POTELIGEO and administer at least 2 weeks of topical corticosteroids. If rash improves to Grade 1 or less, POTELIGEO may be resumed [see Warnings and Precautions (5.1)].
• If mild (Grade 1) rash occurs, consider topical corticosteroids.

Infusion Reactions

• Permanently discontinue POTELIGEO for a life-threatening (Grade 4) infusion reaction [see Warnings and Precautions (5.2)].
• Temporarily interrupt the infusion of POTELIGEO for mild to severe (Grades 1 to 3) infusion reactions and treat symptoms. Reduce the infusion rate by at least 50% when restarting the infusion after symptoms resolve. If reaction recurs and is unmanageable, discontinue infusion. [see Warnings and Precautions (5.2)].
• If an infusion reaction occurs, administer premedication (such as diphenhydramine and acetaminophen) for subsequent POTELIGEO infusions.

2.3 Preparation and Administration

Preparation

• Visually inspect drug product solution for particulate matter and discoloration prior to administration. POTELIGEO is a clear to slightly opalescent colorless solution. Discard the vial if cloudiness, discoloration, or particulates are observed.
• Calculate the dose (mg/kg) and number of vials of POTELIGEO needed to prepare the infusion solution based on patient weight.
• Aseptically withdraw the required volume of POTELIGEO into the syringe and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP. The final concentration of the diluted solution should be between 0.1 mg/mL to 3.0 mg/mL.
• Mix diluted solution by gentle inversion. Do not shake.
• Discard any unused portion left in the vial.

The diluted solution is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags.

Administration

• Administer infusion solution over at least 60 minutes through an intravenous line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter.
• Do not mix POTELIGEO with other drugs.
• Do not co-administer other drugs through the same intravenous line.

Storage of Diluted Solution

After preparation, infuse the POTELIGEO solution immediately, or store under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of infusion preparation.

Do not freeze. Do not shake.

3 DOSAGE FORMS AND STRENGTHS

Injection: 20 mg/5 mL (4 mg/mL) as a clear to slightly opalescent colorless solution in a single-dose vial.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Dermatologic Toxicity

Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of POTELIGEO. Rash (drug eruption) is one of the most common adverse reactions associated with POTELIGEO. In Trial 1, 25% (80/319) of patients treated with POTELIGEO had an adverse reaction of drug eruption, with 18% of these cases being severe (Grade 3) and 82% of these cases being Grade 1 or 2. Of 528 patients treated with POTELIGEO in clinical trials, Grade 3 skin adverse reactions were reported in 3.6%, Grade 4 skin adverse reactions in <1%, and SJS in <1%.

The onset of drug eruption is variable, and the affected areas and appearance vary. In Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. The more common presentations reported included papular or maculopapular rash, lichenoid, spongiotic or granulomatous dermatitis, and morbilliform rash. Other presentations included scaly plaques, pustular eruption, folliculitis, non-specific dermatitis, and psoriasiform dermatitis.

Monitor patients for rash throughout the treatment course. Management of dermatologic toxicity includes topical corticosteroids and interruption or permanent cessation of POTELIGEO [see Dosage and Administration (2.2)]. Consider skin biopsy to help distinguish drug eruption from disease progression.

Discontinue POTELIGEO permanently for SJS or TEN or for any life-threatening (Grade 4) reaction. For possible SJS or TEN, interrupt POTELIGEO and do not restart unless SJS or TEN is ruled out and the cutaneous reaction has resolved to Grade 1 or less.

5.2 Infusion Reactions

Fatal and life-threatening infusion reactions have been reported in patients treated with POTELIGEO. In Trial 1, infusion reactions occurred in 35% (112/319) of patients treated with POTELIGEO, with 8% of these reactions being severe (Grade 3). Most reactions (approximately 90%) occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. The most commonly reported signs include chills, nausea, fever, tachycardia, rigors, headache, and vomiting.

Consider premedication (such as diphenhydramine and acetaminophen) for the first infusion of POTELIGEO in all patients. Whether premedication reduces the risk or severity of these reactions is not established. In Trial 1, infusion reactions occurred in 42% of patients without premedication and 32% of patients with premedication. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly [see Dosage and Administration (2.2)].

5.3 Infections

Fatal and life-threatening infections have occurred in patients treated with POTELIGEO, including sepsis, pneumonia, and skin infection. In Trial 1, 18% (34/184) of patients randomized to POTELIGEO had Grade 3 or higher infection or an infection-related serious adverse reaction. Monitor patients for signs and symptoms of infection and treat promptly.

5.4 Autoimmune Complications

Fatal and life-threatening immune-mediated complications have been reported in recipients of POTELIGEO. Grade 3 or higher immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain-Barré syndrome. Use of systemic immunosuppressants for immune-mediated reactions was reported in 1.9% (6/319) of recipients of POTELIGEO in Trial 1, including for a case of Grade 2 polymyalgia rheumatica. New-onset hypothyroidism (Grade 1 or 2) was reported in 1.3% of patients and managed with observation or levothyroxine. Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.

5.5 Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) after POTELIGEO

Increased risks of transplant complications have been reported in patients who receive allogeneic HSCT after POTELIGEO including severe (Grade 3 or 4) acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and transplant-related death. Among recipients of pre-transplantation POTELIGEO, a higher risk of transplant complications has been reported if POTELIGEO is given within a shorter time frame (approximately 50 days) before HSCT. Follow patients closely for early evidence of transplant-related complications.

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Dermatologic Toxicity [see Warnings and Precautions (5.1)].
• Infusion Reactions [see Warnings and Precautions (5.2)].
• Infections [see Warnings and Precautions (5.3)].
• Autoimmune Complications [see Warnings and Precautions (5.4)].
• Complications of Allogeneic HSCT after POTELIGEO [see Warnings and Precautions (5.5)].

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Trial 1

The data described below reflect exposure to POTELIGEO in a randomized, open-label, actively controlled clinical trial for adult patients with MF or SS who received at least one prior systemic therapy [see Clinical Studies (14)]. Of 370 patients treated, 184 (57% with MF, 43% with SS) received POTELIGEO as randomized treatment and 186 (53% with MF, 47% with SS) received vorinostat. In the vorinostat arm, 135 patients (73%) subsequently crossed over to POTELIGEO for a total of 319 patients treated with POTELIGEO.

POTELIGEO was administered at 1 mg/kg intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of subsequent 28-day cycles. Premedication (diphenhydramine, acetaminophen) was optional and administered to 65% of randomized patients for the first infusion. The comparator group received vorinostat 400 mg orally once daily, given continuously in 28-day cycles. Treatment continued until unacceptable toxicity or progressive disease.

The median age was 64 years (range, 25 to 101 years), 58% of patients were male, 70% were white, and 99% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients had a median of 3 prior systemic therapies. The trial required an absolute neutrophil count (ANC) ≥1500/µL (≥1000/µL if bone marrow was involved), platelet count ≥100,000/µL (≥75,000/µL if bone marrow was involved), creatinine clearance >50 mL/min or serum creatinine ≤1.5 mg/dL, and hepatic transaminases ≤2.5 times upper limit of normal (ULN) (≤5 times ULN if lymphomatous liver infiltration). Patients with active autoimmune disease, active infection, autologous HSCT within 90 days, or prior allogeneic HSCT were excluded.

During randomized treatment, the median duration of exposure to POTELIGEO was 5.6 months, with 48% (89/184) of patients with at least 6 months of exposure and 23% (43/184) with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8 months, with 22% (41/186) of patients with at least 6 months of exposure.

Fatal adverse reactions within 90 days of the last dose occurred in 2.2% (7/319) of patients who received POTELIGEO as randomized or crossover treatment.

Serious adverse reactions were reported in 36% (66/184) of patients randomized to POTELIGEO and most often involved infection (16% of patients; 30/184). Serious adverse reactions reported in >2% of patients randomized to POTELIGEO were pneumonia (5%), sepsis (4%), pyrexia (4%), and skin infection (3%); other serious adverse reactions, each reported in 2% of patients, included hepatitis, pneumonitis, rash, infusion related reaction, lower respiratory tract infection, and renal insufficiency. POTELIGEO was discontinued for adverse reactions in 18% of randomized patients, most often due to rash or drug eruption (7.1%).

Common Adverse Reactions

The most common adverse reactions (reported in ≥20% of patients randomized to POTELIGEO) were rash (including drug eruption), infusion related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain. Other common adverse reactions (reported in ≥10% of patients randomized to POTELIGEO) included skin infection, pyrexia, nausea, edema, thrombocytopenia, headache, constipation, mucositis, anemia, cough and hypertension. Table 1 summarizes common adverse reactions having a ≥2% higher incidence with POTELIGEO than with vorinostat in Trial 1.

Table 1: Common Adverse Reactions (≥10%) with ≥2% Higher Incidence in the POTELIGEO Arm

Other Common Adverse Reactions in ≥10% of POTELIGEO Arm 1, 2

• General disorders: fatigue (31%), edema (16%)
• Gastrointestinal disorders: diarrhea (28%), nausea (16%), constipation (13%)
• Blood and lymphatic system disorders: thrombocytopenia (14%), anemia (12%)
• Nervous system disorders: headache (14%)
• Vascular disorders: hypertension (10%)
• Respiratory disorders: cough (11%)

Adverse Reactions in ≥5% but <10% of POTELIGEO Arm 1, 2

• Infections: candidiasis (9%), urinary tract infection (9%), folliculitis (8%), pneumonia (6%), otitis (5%), herpesvirus infection (5%)
• Investigations: renal insufficiency (9%), hyperglycemia (9%), hyperuricemia (8%), weight increase (8%), weight decrease (6%), hypomagnesemia (6%)
• Psychiatric disorders: insomnia (9%), depression (7%)
• Skin and subcutaneous disorders: xerosis (8%), alopecia (7%)
• Nervous system disorders: dizziness (8%), peripheral neuropathy (7%)
• Metabolism and nutrition disorders: decreased appetite (8%)
• Respiratory disorders: dyspnea (7%)
• General disorders: chills (7%)
• Gastrointestinal disorders: vomiting (7%), abdominal pain (5%)
• Injury, poisoning and procedural complications: fall (6%)
• Musculoskeletal disorders: muscle spasms (5%)
• Cardiovascular disorders: arrhythmia (5%)
• Eye disorders: conjunctivitis (5%)

Selected Other Adverse Reactions 1, 2

• Tumor lysis syndrome (<1%)
• Myocardial ischemia or infarction (<1%)
• Cardiac failure (<1%)

Table 2 summarizes common treatment-emergent laboratory abnormalities having a ≥2% higher incidence with POTELIGEO than with vorinostat.

Table 2: Common New or Worsening Laboratory Abnormalities (≥10%) with ≥2% Higher Incidence in the POTELIGEO Arm

Other common treatment-emergent laboratory abnormalities in the POTELIGEO arm included hyperglycemia (52%; 4% Grade 3-4), anemia (35%; 2% Grade 3-4), thrombocytopenia (29%, none Grade 3-4), aspartate transaminase (AST) increased (25%; 2% Grade 3-4), alanine transaminase (ALT) increased (18%; 1% Grade 3-4), alkaline phosphatase increased (17%; 0% Grade 3-4), and neutropenia (10%; 2% Grade 3-4). Grade 4 treatment-emergent laboratory abnormalities observed in ≥1% of the POTELIGEO arm included lymphopenia (5%), leukopenia (1%), and hypophosphatemia (1%).

1  Includes grouped terms

2  From 184 patients randomized to POTELIGEO

6.2 Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to POTELIGEO with the incidences of antibodies in other studies or to other products may be misleading.

Among 258 patients treated with POTELIGEO in Trial 1, 10 (3.9%) tested positive for treatment-emergent (treatment-induced or treatment-boosted) anti-mogamulizumab-kpkc antibodies by an electrochemiluminescent assay. There were no positive neutralizing antibody responses.

6.3 Postmarketing Safety Information

The following adverse reactions have been identified during post-approval use of POTELIGEO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Infections: Hepatitis B virus reactivation
• Cardiac disorders: Stress cardiomyopathy

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on POTELIGEO use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of mogamulizumab-kpkc to pregnant cynomolgus monkeys from the start of organogenesis through delivery did not show a potential for adverse developmental outcomes at maternal systemic exposures 27 times the exposure in patients at the recommended dose, based on AUC (see Data). In general, IgG molecules are known to cross the placental barrier and in the monkey reproduction study mogamulizumab-kpkc was detected in fetal plasma. Therefore, POTELIGEO has the potential to be transmitted from the mother to the developing fetus. POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Data

Animal Data

The effects of mogamulizumab-kpkc on embryo-fetal development were evaluated in 12 pregnant cynomolgus monkeys that received mogamulizumab-kpkc once weekly by intravenous administration from the start of organogenesis through delivery at an exposure level 27 times higher than the clinical dose. Mogamulizumab-kpkc administration did not show a potential for embryo-fetal lethality, teratogenicity, or fetal growth retardation and did not result in spontaneous abortion or increased fetal death. In surviving fetuses (10 of 12 compared with 11 of 12 in the control group) of cynomolgus monkeys treated with mogamulizumab-kpkc, a decrease in CCR4-expressing lymphocytes due to the pharmacological activity of mogamulizumab-kpkc was noted; there were no apparent mogamulizumab-kpkc -related external, visceral, or skeletal abnormalities.

8.2 Lactation

Risk Summary

There is no information regarding the presence of POTELIGEO in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for POTELIGEO and any potential adverse effects on the breastfed child from POTELIGEO or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception.

Pregnancy Testing

For females of reproductive potential, verify pregnancy status prior to initiating POTELIGEO.

Contraception

Advise females of reproductive potential to use effective contraception during treatment with POTELIGEO and for at least 3 months following the last dose of POTELIGEO.

8.4 Pediatric use

The safety and effectiveness of POTELIGEO in pediatric patients have not been established.

8.5 Geriatric use

Of 319 patients with MF or SS who received POTELIGEO in Trial 1, 162 (51%) were ≥65 years. No overall differences in effectiveness were observed between these patients and younger patients. In patients aged ≥65, Grade 3 or higher adverse reactions were reported in 45% and serious adverse reactions in 36%, whereas in patients aged <65, Grade 3 or higher adverse reactions were reported in 36% and serious adverse reactions in 29%.

11 DESCRIPTION

Mogamulizumab-kpkc is a recombinant humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4)-expressing cells. Mogamulizumab-kpkc is an IgG1 kappa immunoglobulin that has a calculated molecular mass of approximately 149 kDa. Mogamulizumab-kpkc is produced by recombinant DNA technology in Chinese hamster ovary cells.

POTELIGEO (mogamulizumab-kpkc) injection is a sterile, ready-to-use, preservative-free, clear to slightly opalescent colorless solution in a single-dose vial for dilution prior to intravenous infusion. Each vial contains 20 mg of mogamulizumab-kpkc in 5 mL of solution. Each mL of solution contains 4 mg of mogamulizumab-kpkc and is formulated in: citric acid monohydrate (0.44 mg), glycine (22.5 mg), polysorbate 80 (0.2 mg), and Water for Injection, USP. May contain hydrochloric acid/sodium hydroxide to adjust pH to 5.5.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody that binds to CCR4, a G protein-coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. Non-clinical in vitro studies demonstrate mogamulizumab-kpkc binding targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells. CCR4 is expressed on the surface of some T-cell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells.

12.2 Pharmacodynamics

Mogamulizumab-kpkc exposure-response relationships and the time course of pharmacodynamics response are unknown.

12.3 Pharmacokinetics

Mogamulizumab-kpkc pharmacokinetics (PK) was evaluated in patients with T-cell malignancies. Parameters are presented as the geometric mean [% coefficient of variation (%CV)] unless otherwise specified. Mogamulizumab-kpkc concentrations increased proportionally with dose over the dose range of 0.01 to 1.0 mg/kg (0.01 to 1 times the approved recommended dosage).

Following repeated dosing of the approved recommended dosage, steady state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) µg/mL, the trough concentration (Cmin,ss) is 11 (239%) µg/mL, and AUCss is 5577 (125%) µg∙hr/mL.

Distribution

The central volume of distribution is 3.6 L (20%).

Elimination

The terminal half-life is 17 days (66%), and the clearance is 12 mL/h (84%).

Specific Populations:

No clinically significant changes in the PK of mogamulizumab-kpkc were observed based on age (range: 22 to 101 years), sex, ethnicity, renal impairment (creatinine clearance <90 mL/min, estimated by Cockcroft-Gault), mild (total bilirubin ≤ ULN and AST 1.5 to 3 times ULN and any AST) hepatic impairment, disease subtype (MF or SS), degree of CCR4 expression, or ECOG status. The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on mogamulizumab-kpkc PK is unknown.

Drug Interaction Studies

No drug interaction studies have been conducted with POTELIGEO.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

No carcinogenicity or genotoxicity studies have been conducted with POTELIGEO.

No specific studies have been conducted to evaluate potential effects of POTELIGEO on fertility. No mogamulizumab-kpkc -related toxic effects in the male and female reproductive organs were observed in sexually mature monkeys in repeat-dose toxicology studies up to 26 weeks in duration.

14 CLINICAL STUDIES

Trial 1

A randomized, open-label, multicenter trial (Study 0761-010; NCT01728805) evaluated the efficacy of POTELIGEO in adult patients with MF or SS after at least one prior systemic therapy. The trial randomized 372 patients 1:1 to either POTELIGEO (186 patients; 56% with MF, 44% with SS) or vorinostat (186 patients; 53% with MF, 47% with SS). The trial included patients regardless of tumor CCR4 expression status and excluded patients with histologic transformation, prior allogeneic HSCT, autologous HSCT within 90 days, active autoimmune disease, or active infection. The trial required patients to have ANC ≥1500/µL (≥1000/µL if bone marrow was involved), platelet count ≥100,000/µL (≥75,000/µL if bone marrow was involved), creatinine clearance >50 mL/min or serum creatinine ≤1.5 mg/dL and hepatic transaminases ≤2.5 times ULN (≤5 times ULN if lymphomatous liver infiltration).

The dose of POTELIGEO was 1 mg/kg administered intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle. Vorinostat was dosed at 400 mg orally once daily, continuously for 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. Vorinostat-treated patients with disease progression or unacceptable toxicities were permitted to cross over to POTELIGEO.

The median age was 64 years (range: 25 to 101), 58% of patients were male, and 70% were white. At study baseline, 38% had stage IB-II disease, 10% stage III, and 52% stage IV. The median number of prior systemic therapies was 3. In the POTELIGEO arm, baseline CCR4 expression status by immunohistochemistry was available in 140 patients (75%), of whom all had CCR4 detected on ≥1% of lymphocytes on skin biopsy, and 134/140 (96%) had CCR4 detected on ≥10% of the lymphocytes. CCR4 expression status was similar in the vorinostat arm.

During randomized treatment, the median duration of exposure to POTELIGEO was 5.6 months (range: <1 to 45.3 months), with 48% of patients with at least 6 months of exposure and 23% with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8 months (range: <1 to 34.8 months), with 22% of patients with at least 6 months of exposure.

Efficacy was based on investigator-assessed progression-free survival (PFS), which was defined as the time from the date of randomization until documented progression of disease or death. Other efficacy measures included overall response rate (ORR) based on global composite response criteria that combine measures from each disease compartment (skin, blood, lymph nodes and viscera). Responses required confirmation at two successive disease assessments, which included the modified Severity Weighted Assessment Tool, skin photographs, central flow cytometry, and computed tomography.

The trial demonstrated that POTELIGEO significantly prolonged PFS compared to vorinostat (Table 3). The Kaplan-Meier curve for PFS by Investigator is shown in Figure 1. The estimated median follow-up for investigator-assessed PFS was 13 months in the POTELIGEO arm and 10.4 months in the vorinostat arm. By independent review committee assessment, the estimated median PFS was 6.7 months (95% CI, 5.6 to 9.4) in the POTELIGEO arm and 3.8 months (95% CI, 3.0 to 4.7) in the vorinostat arm (hazard ratio 0.64; 95% CI: 0.49, 0.84).

Figure 1 Kaplan-Meier Curve for Progression-Free Survival per Investigator

Table 3 also summarizes investigator-assessed confirmed response rates, overall and by disease compartment. The trial demonstrated improvement in ORR with POTELIGEO.

Table 3 Efficacy of Randomized Treatment (Trial 1)

16 HOW SUPPLIED/STORAGE AND HANDLING

POTELIGEO (mogamulizumab-kpkc) injection is a sterile, preservative-free, clear to slightly opalescent colorless solution supplied in a carton containing one 20 mg/5 mL (4 mg/mL), single-dose glass vial (NDC 42747-761-01).

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original package to protect from light until time of use. Do not freeze. Do not shake.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Inform patients of the risk of the following adverse reactions that may require additional treatment and/or withholding or discontinuation of POTELIGEO including:

• Dermatological Toxicity: Advise patients to contact their healthcare provider immediately for new or worsening skin rash [see Warnings and Precautions (5.1)]. Advise patients that the rash can happen at any time while receiving POTELIGEO.
• Infusion Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion reactions [see Warnings and Precautions (5.2)].
• Infections: Advise patients to contact their health care provider for fever or other evidence of infection [see Warnings and Precautions (5.3)].
• Autoimmune Complications: Advise patients to notify their healthcare provider of any history of autoimmune disease [see Warnings and Precautions (5.4)].
• Complications of Allogeneic HSCT after POTELIGEO: Advise patients of potential risk of post-transplant complications [see Warnings and Precautions (5.5)].
• Females of Reproductive Potential: Advise use of effective contraception during treatment with POTELIGEO and for at least 3 months following the last dose of POTELIGEO [see Use in Specific Populations (8.3)].

POTELIGEO® (mogamulizumab-kpkc)
Manufactured by:
Kyowa Kirin, Inc.
Bedminster, NJ 07921
US License No. 2077

PRINCIPAL DISPLAY PANEL - 4 mg/mL Vial Carton

Rx only

NDC 42747-761-01

POTELIGEO®
(mogamulizumab-kpkc)

Injection

20 mg/5 mL
(4 mg/mL)

For Intravenous Infusion

Single-dose vial.
Discard unused portion.

【备注】以上内容仅供参考，不作为用药依据，详情请参照药品附带说明书。