近日，美国FDA批准Opdivo(nivolumab)新适应症；为治疗晚期黑色素瘤、小细胞肺癌、经典霍奇金淋巴瘤、肝细胞癌、头颈部鳞状细胞癌、晚期肾细胞癌、晚期或转移性尿路上皮癌的患者

批准日期：2014年12月22日；公司：施贵宝公司

OPDIVO（纳武单抗 nivolumab）注射液，用于静脉注射

美国最初批准：2014年

最近的重大变化

适应症和用法：4/2018

剂量和用法：4/2018

警告和注意事项：4/2018

作用机制

PD-1配体PD-L1和PD-L2与T细胞上发现的PD-1受体的结合抑制T细胞增殖和细胞因子产生。

在一些肿瘤中发生PD-1配体的上调，并且通过该途径的信号传导有助于抑制肿瘤的活性T细胞免疫监视。

PD-L1和PD-L2，释放PD-1途径介导的免疫应答抑制，包括抗肿瘤免疫应答。

在同系小鼠肿瘤模型中，阻断PD-1活性导致肿瘤生长减少。

合并nivolumab（抗PD-1）和易普利姆玛（抗CTLA-4）介导的抑制的结果inenhanced T细胞功能比单独的任一种抗体的作用更大，并且结果inimproved在转移性黑色素瘤和晚期RCC抗肿瘤反应。

在鼠类syngeneictumor模型中，PD-1和CTLA-4的双重阻断导致抗肿瘤活性增加。

适应症和用法

OPDIVO是indicatedfor治疗的程序性死亡受体-1（PD-1）阻断抗体：患者BRAF V600野生型不能切除或转移性黑色素瘤，作为单一药剂。

BRAF V600突变阳性患者无法切除或转移

黑色素瘤，作为单一药剂.a。

患有不可切除或转移性黑色素瘤的患者，联合皮利姆单抗。

在辅助治疗中，患有淋巴结受累或转移性疾病的黑色素瘤患者已经完全切除。

例转移性非小细胞肺癌和进展上orafter基于铂的化疗。患者EGFR或ALK genomictumor像差应该对FDA-approvedtherapy为之前接收OPDIVO这些像差疾病进展。

已接受过抗血管生成治疗的晚期肾细胞癌患者。

患有中度或低风险的患者，既往未治疗的晚期肾细胞癌，联合ipilimumab。

经历过复发或进展的经典霍奇金淋巴瘤的成年患者：

自体造血干细胞移植（HSCT）andbrentuximab vedotin，或包括自体造血干细胞移植的全身性治疗的3行或更多行。

患有复发性或转移性头颈部鳞状细胞癌的患者，在铂类治疗之后或之后疾病进展。

例局部晚期或转移性泌尿道上皮癌whob：具有在疾病进展期间或12个月的新辅助或adjuvanttreatment的内下面的铂 - containingchemotherapyhave疾病进展与含铂的化疗。

成人和儿童（12岁以上）患者microsatelliteinstability高（MSI-H）或错配修复已经取得进展在与afluoropyrimidine，奥沙利铂和irinotecan.b治疗缺陷（dMMR）metastaticcolorectal癌症。

曾接受过索拉非尼治疗的肝细胞癌患者。

该指征的持续批准可能仅限于在验证试验中验证和描述临床益处。

对该指征的持续批准可能取决于确认试验中的临床益处的验证和描述。

剂量和用量

在30分钟内将OPDIVO作为静脉输注给药。

不可切除或转移性黑色素瘤

OPDIVO每2周240毫克或每4周480毫克。

OPDIVO与易普利姆玛：OPDIVO为1mg/kg时，随后ipilimumabon同一天，每3周4次剂量，然后OPDIVO 240毫克every2周或480毫克每4周。

辅助治疗黑色素瘤

OPDIVO每2周240毫克或每4周480毫克。

转移性非小细胞肺癌

OPDIVO每2周240毫克或每4周480毫克。

晚期肾细胞癌

OPDIVO每2周240毫克或每4周480毫克。

OPDIVO与易普利姆玛：OPDIVO 3毫克/千克，接着易普利姆玛为1mg/kg的同一天，每3周4次剂量，然后OPDIVO 240毫克，每2周或480毫克每4周。

经典霍奇金淋巴瘤

OPDIVO每2周240毫克或每4周480毫克。

复发或头颈部OPDIVO的转移性鳞状细胞癌的240毫克每2周或480毫克每4周。

局部OPDIVO每2周240毫克或每4周480毫克。

微卫星不稳定性高（MSI-H）或错配修复缺陷（dMMR）转移性结直肠癌OPDIVO 240毫克每2周。

肝细胞癌

OPDIVO每2周240毫克或每4周480毫克。

剂量形式和强度

注射：40毫克/4mL，100毫克/10毫升，240毫克/24毫升在单剂量小瓶溶液。

禁忌症

无。

警告和注意事项

免疫介导性肺炎：暂停对中度和permanentlydiscontinue严重或危及生命的肺炎。

当以单一agentfor中度或重度给出并且在与易普利姆玛中度给出andpermanently停止对严重或危及生命的结肠炎生命threateningcolitis扣压OPDIVO永久停止免疫介导的结肠炎:扣压OPDIVO。

免疫介导的肝炎：监测肝功能的变化。保留中度和永久性中断严重或危及生命的转氨酶或总胆红素升高。

免疫介导的内分泌疾病：扣留中度或重度andpermanently停止对危及生命的垂体扣压formoderate并永久停止对严重或危及生命的肾上腺机能不全监视器甲状腺功能变化启动thyroidhormone更换需要监控高血糖扣压forsevere并永久停止危及生命的高血糖症。

免疫介导的肾炎和肾功能不全。保留中度或重度并永久性地停止危及生命的血清肌酐升高。

免疫介导的皮肤不良反应：坚持严重和永久停止危及生命的皮疹。

免疫介导的脑炎：监测神经功能的变化。

扣压新发中度至重度神经系统体征或symptomsand永久停止对免疫介导性脑炎。

输液反应：..请停止OPDIVO严重和生活threateninginfusion反应中断或减慢输液速度患者mildor中度输液反应。

同种异体HSCT的并发症OPDIVO:监视器后hyperacutegraft抗宿主病（GVHD），3-4级急性GVHD，类固醇，需要发热综合征，肝静脉闭塞性疾病，和otherimmune介导的不良反应移植相关死亡率hasoccurred。

胚胎 - 胎儿毒性:.能引起的潜在风险胎儿造成伤害奉劝afetus和使用有效避孕。

不良反应

患者最常见的不良反应（20％）为：

OPDIVO作为单一药剂：疲劳，皮疹，肌肉骨骼疼痛，瘙痒，腹泻，恶心，虚弱，咳嗽，呼吸困难，便秘，食欲不振，背痛，关节痛，上呼吸道感染，发热，头痛，和腹痛降低。

OPDIVO与易普利姆玛黑色素瘤：乏力，皮疹，腹泻，恶心，发热，呕吐和呼吸困难。

OPDIVO与易普利姆玛用于肾细胞癌：乏力，皮疹，腹泻，肌肉疼痛，皮肤瘙痒，恶心，咳嗽，发热，关节痛，食欲anddecreased。

要报告疑似不良反应，请联系布里斯托尔-MyersSquibb在1-800-721-5072或FDA电话：1-800-FDA-1088 orwww.fda.gov/medwatch。

用于特定人群

哺乳期：停止母乳喂养。

包装提供/存储和处理

OPDIVO（nivolumab）注射剂如下：

纸箱内容                   NDC

40mg/4mL单剂量小瓶     0003-3772-11

100mg/10mL单剂量小瓶   0003-374-12

240mg/24mL单剂量小瓶   0003-3734-13

将OPDIVO储存在2°C至8°C（36°F至46°F）的冷藏温度下。保护OPDIVO不受光照影响

不要冻结或摇晃。

file:///C:/Users/Administrator/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.IE5/X3L8H68Y/125554s058lbl.pdf

Opdivo (Nivolumab Injection) 

FULL INDICATIONS

For Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (1 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat a type of advanced stage lung cancer (called non-small cell lung cancer) that has spread or grown and you have tried chemotherapy that contains platinum, and it did not work or is no longer working. If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these

abnormal genes, and it did not work or is no longer working.

For Patients With Metastatic Melanoma (2 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma). OPDIVO is approved for both BRAF+ and BRAF- patients. OPDIVO was approved for BRAF+ metastatic melanoma patients based on the amount of time patients lived without their tumors worsening. There is ongoing eva luation of clinical benefit of OPDIVO for this use.

OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat a type of skin cancer called melanoma that has spread or cannot be removed by surgery (advanced melanoma). OPDIVO in combination with YERVOY was approved based on the amount of time patients lived without their tumors worsening. There is ongoing eva luation of clinical benefit of OPDIVO in combination with YERVOY for this use.

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

To Help Prevent a Skin Cancer Called Melanoma From Coming Back After It and the Affected Lymph Nodes Have Been Removed by Surgery (3 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat people with a type of skin cancer called melanoma to help prevent melanoma from coming back after it and lymph nodes that contain cancer have been removed by surgery.

For Adults With Kidney Cancer (Renal Cell Carcinoma) That Has Spread (4 of 10)

OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) to treat kidney cancer (renal cell carcinoma) in certain people when their cancer has spread.

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

For Previously Treated Patients With Advanced Renal Cell Carcinoma (5 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat kidney cancer (renal cell carcinoma) when your cancer has spread or grown after treatment with other cancer medications.

For Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN) That Has Returned or Spread After Previous Treatment (6 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat head and neck cancer (squamous cell carcinoma) that has come back or spread and you have tried chemotherapy that contains platinum and it did not work or is no longer working.

For People With Liver Cancer (Hepatocellular Carcinoma) That Have Received Treatment With Nexavar® (sorafenib) (7 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat people with liver cancer (hepatocellular carcinoma) after you have received treatment with Nexavar® (sorafenib). OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing eva luation of clinical benefit of OPDIVO for this use.

For Previously Treated Patients With Advanced Bladder Cancer (Urothelial Carcinoma) (8 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat bladder cancer (urothelial carcinoma) that has spread or grown and you have tried chemotherapy that contains platinum, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing eva luation of clinical benefit of OPDIVO for this use.

For People 12 Years of Age and Older Whose CRC Has Spread to Other Parts of the Body (Metastatic), Has Progressed After Treatment With a Fluoropyrimidine, Oxaliplatin, and Irinotecan, and Is dMMR or MSI-H (9 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat adults and children 12 years of age and older with a type of colon or rectal cancer (colorectal cancer) that has spread to other parts of the body (metastatic), is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and you have tried chemotherapy with a fluoropyrimidine, oxaliplatin, and irinotecan, and it did not work or is no longer working. OPDIVO was approved based on response rate and how long patients’ responses lasted. There is ongoing eva luation of clinical benefit of OPDIVO for this use.

For Adults With classical Hodgkin Lymphoma Whose Cancer has Come Back or Spread After an Autologous Stem Cell Transplant and Treatment With Adcetris® (brentuximab vedotin) or After 3 or More Kinds of Treatment Including an Autologous Stem Cell Transplant (10 of 10)

OPDIVO® (nivolumab) is a prescription medicine used to treat adults with a type of blood cancer called classical Hodgkin lymphoma if your cancer has come back or spread after a type of stem cell transplant that uses your own stem cells (autologous), and you used the drug brentuximab vedotin (Adcetris®) before or after your stem cell transplant, or if you received at least 3 kinds of treatment including an autologous stem cell transplant. OPDIVO was approved based on response rate. There is ongoing eva luation of clinical benefit of OPDIVO for this use.

It is not known if OPDIVO is safe and effective in children less than 18 years of age.

It is not known if OPDIVO is safe and effective in children less than 12 years of age with MSI-H or dMMR metastatic colorectal cancer, or in children less than 18 years of age for the treatment of any other cancers.