Opdivo Qvantig

任意数量

is the first and only subcutaneously administered PD-1 inhibitor

是第一个也是唯一一个皮下注射的PD-1抑制剂

Given over three- to five-minutes,

，

Opdivo Qvantig

Opdivo Qvantig

demonstrated consistent efficacy and showed a comparable safety profile to

表现出一致的疗效，并显示出与

intravenous

静脉注射

Opdivo

奇妙

in the Phase 3 CheckMate-67T trial PRINCETON, N.J.--(BUSINESS WIRE)--

在第三阶段CheckMate-67T试验中，新泽西州普林斯顿（商业新闻）--

Bristol Myers Squibb

百时美施贵宝

(NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) granted approval for

（纽约证券交易所：BMY）今天宣布，美国食品和药物管理局（FDA）批准了

Opdivo Qvantig™

任意数量™

(nivolumab and hyaluronidase-nvhy) injection

（nivolumab和透明质酸酶nvhy）注射液

for subcutaneous use, a combination product of nivolumab

对于皮下使用，nivolumab的组合产品

co-formulated with recombinant human hyaluronidase (rHuPH20), in most previously approved adult, solid tumor

与重组人透明质酸酶（rHuPH20）共同配制，用于大多数先前批准的成人实体瘤

Opdivo

Opdivo

indications as monotherapy, monotherapy maintenance following completion of

适应症为单一疗法，完成后维持单一疗法

Opdivo

奇妙

plus

加

Yervoy®

易普利姆玛®

(ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib.1,2

（ipilimumab）联合治疗，或联合化疗或cabozantinib。1,2

The approval is based on the results from the Phase 3 randomized, open-label CheckMate-67T trial, which demonstrated non-inferior co-primary pharmacokinetic (PK) exposures, similar efficacy in overall response rate (ORR), and showed a comparable safety profile vs.

。

intravenous (IV) .

静脉注射（IV）。

Opdivo

Opdivo

.1,3

.1,3

Opdivo Qvantig™ (nivolumab and hyaluronidase-nvhy) Logo (Credit: Bristol Myers Squibb)

Opdivo Qvantig™（nivolumab和透明质酸酶nvhy）徽标（来源：百时美施贵宝）

“This approval of subcutaneous nivolumab gives our patients a new option that can deliver consistent efficacy and comparable safety expected from IV nivolumab, and offers a patient-centric treatment experience,” said Professor Dr. Saby George, MD, FACP, medical oncologist and director of network clinical trials at Roswell Park Comprehensive Cancer Center.1.

Roswell Park综合癌症中心医学肿瘤学家兼网络临床试验主任Saby George教授说：“皮下注射nivolumab的批准为我们的患者提供了一种新的选择，可以提供IV nivolumab预期的一致疗效和可比安全性，并提供以患者为中心的治疗体验。”。

“

“

Opdivo Qvantig

Opdivo Qvantig

offers faster administration*, delivered in three to five minutes. It may allow patients, in consultation with their doctors, to choose another treatment method and the flexibility to receive treatment closer to home.”1,2

提供更快的管理*，只需三到五分钟即可完成。它可以让患者在咨询医生后选择另一种治疗方法，并可以灵活地在离家较近的地方接受治疗。”1,2个

In the trial, noninferiority was demonstrated for the co-primary endpoints of time-averaged concentration over 28 days (C

在试验中，28天内时间平均浓度的共同主要终点显示出非劣效性（C

avgd28

gd28

) and minimum concentration at steady state (C

)和稳态下的最小浓度（C

minss

分钟

) of

)的

Opdivo Qvantig

任意数量

vs. IV

对比IV

Opdivo

奇妙

.1,3

.1,3

The geometric mean ratios (GMRs) for C

C的几何平均比（GMR）

avgd28

gd28

was 2.10 (90% CI: 2.00-2.20) and the GMR for C

C的GMR为2.10（90%置信区间：2.00-2.20）

minss

分钟

was 1.77 (90% CI: 1.63-1.93).1

为1.77（90%置信区间：1.63-1.93）

As a key powered secondary endpoint, the overall response rate (ORR) in the

作为一个关键的辅助终点，总体响应率（ORR）在

Opdivo Qvantig

任意数量

arm (n=248) was 24% (95% CI: 19-30) compared with 18% (95% CI: 14-24) in the IV

手臂（n=248）为24%（95%置信区间：19-30），而静脉注射为18%（95%置信区间：14-24）

Opdivo

Opdivo

arm (n=247), showing that

手臂（n=247），表明

Opdivo Qvantig

Opdivo Qvantig

has similar efficacy compared to IV

与IV相比具有相似的功效

Opdivo

奇妙

.1

.1

Subcutaneous administration may offer flexibility to receive treatment where it is best for patients and their providers, and may reduce steps required for preparation and time needed for administration.5,6,7,8,9,10

皮下给药可以提供灵活性，以便在最适合患者及其提供者的情况下接受治疗，并可以减少准备所需的步骤和给药所需的时间。5,6,7,8,9,10

In the CM–67T trial, average administration time with

Opdivo Qvantig

Opdivo Qvantig

was approximately five minutes, and most patients received all doses of the study medication without an injection interruption or dose delay.3

大约五分钟，大多数患者接受了所有剂量的研究药物，没有注射中断或剂量延迟。3

With this approval,

经批准，

Opdivo Qvantig

任意数量

is now the first and only subcutaneously administered PD-1 inhibitor, offering a faster delivery for patients to receive this immunotherapy treatment option in three to five minutes compared to 30-minute IV

是目前第一种也是唯一一种皮下注射的PD-1抑制剂，与静脉注射30分钟相比，在三到五分钟内为患者提供了更快的分娩速度

Opdivo

Opdivo

.1,2

.1,2

Opdivo

奇妙

and

和

Opdivo Qvantig

Opdivo Qvantig

are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when .

与以下警告和注意事项相关：严重和致命的免疫介导的不良反应，包括肺炎，结肠炎，肝炎和肝毒性，内分泌病，肾功能不全的肾炎，皮肤病不良反应，其他免疫介导的不良反应；异基因造血干细胞移植（HSCT）的并发症；胚胎-胎儿毒性；并增加多发性骨髓瘤患者的死亡率。

Opdivo

奇妙

or

或

Opdivo Qvantig

任意数量

are added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

被添加到沙利度胺类似物和地塞米松中，这在对照临床试验之外是不推荐的。

Opdivo

奇妙

is associated with infusion related reactions. Please see Important Safety Information below.

与输液相关的反应有关。请参阅下面的重要安全信息。

“At Bristol Myers Squibb, we are committed to helping patients in all aspects of their healthcare journey,” said

“在百时美施贵宝，我们致力于帮助患者在医疗保健过程的各个方面，”他说

Adam Lenkowsky, executive vice president and chief commercialization officer. “Over the last decade,

AdamLenkowsky，执行副总裁兼首席商业化官。“在过去十年中，

Opdivo

Opdivo

has evolved as an immunotherapy option used in many indications across tumor types.9

已经发展成为一种免疫治疗选择，用于多种肿瘤类型的适应症

With this new option, we look forward to further helping cancer patients with an administration method that gives them

有了这个新的选择，我们期待着进一步帮助癌症患者的管理方法，使他们

faster delivery.”1,2

更快的交付。”1,2个

“Receiving a cancer diagnosis can be frightening and stressful,” said Audrey Davis, LPC and Senior Director of Programs and Health Equity at the Cancer Support Community. “Having a treatment option that may offer patients flexibility to receive treatment outside of traditional hospital settings and reduce the administration time is important.7,8,9,10.

LPC和癌症支持社区项目与健康公平高级主管奥黛丽·戴维斯（AudreyDavis）说：“接受癌症诊断可能会让人感到恐惧和压力。”。“有一种治疗选择，可以为患者提供在传统医院环境之外接受治疗的灵活性，并减少给药时间，这一点很重要。7,8,9,10。

It’s exciting to see these continued advancements with immunotherapy administration that may offer another choice for patients and caregivers navigating this difficult journey.”9

看到免疫治疗管理的这些持续进步令人兴奋，这可能为患者和护理人员在这段艰难的旅程中提供另一种选择。”9

*Refers to the injection time and does not include other aspects of treatment; actual clinic time may vary.

*指注射时间，不包括治疗的其他方面；实际就诊时间可能会有所不同。

About CheckMate-67T

关于CheckMate-67T

CheckMate-67T was a Phase 3, randomized, open-label, noninferiority trial evaluating

CheckMate-67T是一项3期，随机，开放标签，非劣效性试验

Opdivo Qvantig

任意数量

compared to intravenous (IV)

与静脉注射（IV）相比

Opdivo

奇妙

, in adult patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy.1,3

，在接受过全身治疗的晚期或转移性透明细胞肾细胞癌（ccRCC）的成年患者中。1,3

A total of 495 patients were randomized to receive either

共有495名患者被随机分配接受

Opdivo Qvantig

Opdivo Qvantig

(1,200 mg of nivolumab and 20,000 units of hyaluronidase) every 4 weeks subcutaneously (n = 248), or

（每4周皮下注射1200 mg nivolumab和20000单位透明质酸酶）（n=248），或

Opdivo

奇妙

3 mg/kg every 2 weeks intravenously (n = 247).1

每2周静脉注射3 mg/kg（n=247）

The coprimary endpoints were time-averaged concentration over 28 days (C

主要终点为28天内的时间平均浓度（C

avgd28

gd28

) and minimum concentration at steady state (C

)和稳态下的最小浓度（C

minss

分钟

).1,3

).1,3

The key powered secondary endpoint was overall response rate, as assessed by blinded independent central review.2

通过盲法独立中央审查评估，关键的次要终点是总体缓解率。2

Select Safety Profile from CheckMate-67T

从CheckMate-67T中选择安全配置文件

Serious adverse reactions occurred in 28% of patients receiving

接受治疗的患者中有28%发生严重不良反应

Opdivo Qvantig

Opdivo Qvantig

(n=247).1

（n=247）

The most frequent serious adverse reactions reported in >1% of patients who received

超过1%的患者报告了最常见的严重不良反应

Opdivo Qvantig

Opdivo Qvantig

were pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%).1

胸腔积液（1.6%），肺炎（1.6%），高血糖（1.2%），高钾血症（1.2%），出血（1.2%）和腹泻（1.2%）

The most common adverse reactions (≥10%) in patients treated with

Opdivo Qvantig

任意数量

(n=247) were musculoskeletal pain (31%), fatigue (20%), pruritus (16%), rash (15%), hypothyroidism (12%), diarrhea (11%), cough (11%), and abdominal pain (10%). Fatal adverse reactions occurred in 3 (1.2%) patients who received

（n=247）为肌肉骨骼疼痛（31%），疲劳（20%），瘙痒（16%），皮疹（15%），甲状腺功能减退（12%），腹泻（11%），咳嗽（11%）和腹痛（10%）。3例（1.2%）患者发生致命不良反应

Opdivo Qvantig

任意数量

; these included myocarditis, myositis, and colitis complications.1

；这些包括心肌炎，肌炎和结肠炎并发症。1

Study therapy was discontinued in 10% of patients due to adverse reactions.1

The safety profile of

的安全概况

Opdivo Qvantig

Opdivo Qvantig

was comparable with the safety profile of IV

与IV的安全性相当

Opdivo

Opdivo

.1

.1

About Subcutaneous Administration

关于皮下给药

Subcutaneous administration is delivery of treatment beneath the skin and is an alternative to IV infusion.10

There are several potential benefits of subcutaneous administration: it may offer the flexibility to provide and receive treatment where it is best for the healthcare provider and patient, may impact infusion chair capacity, and may reduce time spent preparing and administering treatment.5,6,7,8,9,10.

皮下给药有几个潜在的好处：它可以提供灵活性，以提供和接受最适合医疗保健提供者和患者的治疗，可能会影响输液椅的容量，并可能减少准备和管理治疗所花费的时间。5,6,7,8,9,10。

It may also simplify administering treatment for patients who have difficult-to-access veins or do not want a port.11

它还可以简化难以进入静脉或不想要端口的患者的治疗

Subcutaneous treatment has the potential to be administered by a healthcare professional without site of care restrictions.9

皮下治疗有可能由医疗保健专业人员进行，而不受护理部位的限制。9

INDICATIONS

适应症

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC), following treatment with intravenous nivolumab and ipilimumab combination therapy.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于静脉注射nivolumab和ipilimumab联合治疗后的中危或低危晚期肾细胞癌（RCC）成年患者的一线治疗。

Limitations of Use:

使用限制：

OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of renal cell carcinoma.

OPDIVO QVANTIG未与ipilimumab联合用于治疗肾细胞癌。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), in combination with cabozantinib, is indicated for the first- line treatment of adult patients with advanced renal cell carcinoma (RCC).

OPDIVO QVANTIG™（nivolumab和透明质酸酶）与cabozantinib联合用于成人晚期肾细胞癌（RCC）患者的一线治疗。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于治疗先前接受过抗血管生成治疗的成年晚期肾细胞癌（RCC）患者。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with unresectable or metastatic melanoma.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于治疗无法切除或转移性黑色素瘤的成年患者。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with unresectable or metastatic melanoma following treatment with intravenous nivolumab and ipilimumab combination therapy.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于静脉注射nivolumab和ipilimumab联合治疗后无法切除或转移性黑色素瘤的成年患者。

Limitations of Use:

使用限制：

OPDIVO QVANTIG is not indicated in combination with ipilimumab for treatment of unresectable or metastatic melanoma.

OPDIVO QVANTIG未与ipilimumab联合用于治疗不可切除或转移性黑色素瘤。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the adjuvant treatment of adult patients with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于完全切除的IIB期，IIC期，III期或IV期黑色素瘤成年患者的辅助治疗。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

OPDIVO QVANTIG™（nivolumab和透明质酸酶）与铂类双联化疗联合使用，可作为可切除（肿瘤≥4 cm或淋巴结阳性）非小细胞肺癌（NSCLC）成年患者的新辅助治疗。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable (tumors >/=4 cm or node positive) non- small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO QVANTIG as monotherapy in the adjuvant setting after surgical resection..

OPDIVO QVANTIG™（nivolumab和透明质酸酶）联合铂类双联化疗，适用于可切除（肿瘤>/=4 cm或淋巴结阳性）非小细胞肺癌（NSCLC）且无已知表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排的成年患者的新辅助治疗，其次是单药OPDIVO QVANTIG作为手术切除后辅助治疗的单一疗法。。

OPDIVO QVANTIG ™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO QVANTIG..

。患有EGFR或ALK基因组肿瘤畸变的患者在接受OPDIVO QVANTIG之前，应在FDA批准的这些畸变治疗中取得疾病进展。。

Limitations of Use:

使用限制：

OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of metastatic NSCLC.

OPDIVO QVANTIG未与ipilimumab联合用于治疗转移性NSCLC。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于治疗成年头颈部复发或转移性鳞状细胞癌（SCCHN）患者，铂类治疗时或治疗后疾病进展。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于成人尿路上皮癌（UC）患者的辅助治疗，这些患者在接受根治性UC切除术后复发风险很高。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC).

OPDIVO QVANTIG™（nivolumab和透明质酸酶）与顺铂和吉西他滨联合用于成人不可切除或转移性尿路上皮癌（UC）患者的一线治疗。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy..

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于治疗局部晚期或转移性尿路上皮癌（UC）的成年患者，这些患者在含铂化疗期间或之后有疾病进展，或者在新辅助治疗或含铂化疗辅助治疗的12个月内有疾病进展。。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase), as monotherapy, is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO QVANTIG™（nivolumab和透明质酸酶）作为单一疗法，适用于接受新辅助放化疗（CRT）的成年患者中完全切除的食管或胃食管交界癌伴残留病理性疾病的辅助治疗。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase) in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO QVANTIG™（nivolumab和透明质酸酶）联合含氟嘧啶和铂的化疗，适用于不可切除的晚期或转移性食管鳞状细胞癌（ESCC）成年患者的一线治疗。

Limitations of Use:

使用限制：

OPDIVO QVANTIG is not indicated in combination with ipilimumab for the treatment of patients with unresectable advanced or metastatic ESCC.

OPDIVO QVANTIG未与ipilimumab联合用于治疗不可切除的晚期或转移性ESCC患者。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase) as monotherapy, is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

。

OPDIVO QVANTIG™ (nivolumab and hyaluronidase) in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

OPDIVO QVANTIG™（nivolumab和透明质酸酶）联合含氟嘧啶和铂的化疗，适用于治疗晚期或转移性胃癌，胃食管连接癌和食管腺癌的成年患者。

IMPORTANT SAFETY INFORMATION

重要安全信息

Severe and Fatal Immune-Mediated Adverse Reactions

严重和致命的免疫介导的不良反应

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO QVANTIG. Early identification and management are essential to ensure safe use of OPDIVO QVANTIG.

免疫介导的不良反应可能严重或致命，可能发生在任何器官系统或组织中。虽然免疫介导的不良反应通常在治疗期间表现出来，但它们也可能在停用OPDIVO QVANTIG后发生。早期识别和管理对于确保OPDIVO QVANTIG的安全使用至关重要。

Monitor for signs and symptoms that may be clinical manifestations of underlying immune- mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection.

监测可能是潜在免疫介导的不良反应的临床表现的体征和症状。在基线和治疗期间定期评估临床化学物质，包括肝酶，肌酐和甲状腺功能。在疑似免疫介导的不良反应的情况下，启动适当的检查以排除其他病因，包括感染。

Institute medical management promptly, including specialty consultation as appropriate..

及时进行医疗管理，包括适当的专业咨询。。

Withhold or permanently discontinue OPDIVO QVANTIG depending on severity [please see Section 2 Dosage and Administration in the accompanying Full Prescribing Information]. In general, if OPDIVO QVANTIG interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less.

根据严重程度，扣留或永久停用OPDIVO QVANTIG[请参阅随附的完整处方信息中的第2节剂量和给药]。一般来说，如果需要中断或停用OPDIVO QVANTIG，则给予全身皮质类固醇治疗（1至2 mg/kg/天泼尼松或等效药物），直到改善至1级或更低。

Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over for at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy..

在改善至1级或更低级别后，开始逐渐减少皮质类固醇，并继续逐渐减少至少1个月。对于免疫介导的不良反应不能用皮质类固醇治疗控制的患者，考虑使用其他全身免疫抑制剂。。

Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

下面讨论不一定需要全身类固醇（例如内分泌病和皮肤病反应）的不良反应的毒性管理指南。

Immune-Mediated Pneumonitis

免疫介导性肺炎

OPDIVO QVANTIG can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

OPDIVO QVANTIG可引起免疫介导的肺炎。先前接受过胸部放疗的患者肺炎的发生率较高。

Immune-mediated pneumonitis occurred in 2.8% (7/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (0.8%) and Grade 2 (2.0%) adverse reactions.

接受OPDIVO QVANTIG治疗的患者中有2.8%（7/247）发生免疫介导的肺炎，包括3级（0.8%）和2级（2.0%）不良反应。

Immune-Mediated Colitis

免疫介导的结肠炎

OPDIVO QVANTIG can cause immune-mediated colitis. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid- refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies..

OPDIVO QVANTIG可引起免疫介导的结肠炎。结肠炎定义中的常见症状是腹泻。据报道，皮质类固醇难治性免疫介导的结肠炎患者巨细胞病毒（CMV）感染/再激活。在皮质类固醇难治性结肠炎的情况下，考虑重复感染性检查以排除其他病因。。

Immune-mediated colitis occurred in 2.8% (7/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (0.4%) and Grade 2 (2.4%) adverse reactions.

接受OPDIVO QVANTIG治疗的患者中有2.8%（7/247）发生免疫介导的结肠炎，包括3级（0.4%）和2级（2.4%）不良反应。

Immune-Mediated Hepatitis and Hepatotoxicity

免疫介导的肝炎和肝毒性

OPDIVO QVANTIG can cause immune-mediated hepatitis.

OPDIVO QVANTIG可引起免疫介导的肝炎。

Immune-mediated hepatitis occurred in 2.4% (6/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (1.6%), and Grade 2 (0.8%) adverse reactions. Intravenous nivolumab in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to intravenous nivolumab alone.

接受OPDIVO QVANTIG治疗的患者中有2.4%（6/247）发生免疫介导的肝炎，包括3级（1.6%）和2级（0.8%）不良反应。与单独静脉注射nivolumab相比，静脉注射nivolumab联合cabozantinib可引起肝毒性，3级和4级ALT和AST升高的频率更高。

Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. With the combination of intravenous nivolumab and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% (35/320) of patients..

与作为单一药物给药时相比，考虑更频繁地监测肝酶。静脉注射nivolumab和cabozantinib联合治疗后，11%（35/320）的患者出现3级和4级ALT或AST升高。。

Immune-Mediated Endocrinopathies

免疫介导的内分泌病

OPDIVO QVANTIG can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO QVANTIG depending on severity [please see section 2 Dosage and Administration in the accompanying Full Prescribing Information].

OPDIVO QVANTIG可引起原发性或继发性肾上腺皮质功能不全，免疫介导的垂体炎，免疫介导的甲状腺疾病和1型糖尿病，可伴有糖尿病酮症酸中毒。根据严重程度扣留OPDIVO QVANTIG[请参阅随附的完整处方信息中的第2节剂量和给药]。

For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated.

对于2级或更高级别的肾上腺功能不全，开始对症治疗，包括临床指示的激素替代。垂体炎可出现与肿块效应相关的急性症状，例如头痛，畏光或视野缺损。垂体炎可引起垂体功能减退；根据临床指示开始激素替代。

Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated..

甲状腺炎可伴有或不伴有内分泌病。甲状腺功能减退症可继发甲状腺功能亢进症；根据临床指示开始激素替代或医疗管理。监测患者的高血糖或其他糖尿病体征和症状；根据临床指示开始胰岛素治疗。。

Adrenal insufficiency occurred in 2% (5/247) of patients receiving OPDIVO QVANTIG, including Grade 3 (0.8%) and Grade 2 (1.2%) adverse reactions. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received intravenous nivolumab with cabozantinib, including Grade 3 (2.2%) and Grade 2 (1.9%) adverse reactions.

接受OPDIVO QVANTIG治疗的患者中有2%（5/247）发生肾上腺功能不全，包括3级（0.8%）和2级（1.2%）不良反应。接受卡博替尼静脉注射nivolumab的RCC患者中有4.7%（15/320）发生肾上腺功能不全，包括3级（2.2%）和2级（1.9%）不良反应。

Hypophysitis occurred in 0.6% (12/1994) of patients treated with single agent intravenous nivolumab, including Grade 3 (0.2%) and Grade 2 (0.3%). Thyroiditis occurred in 0.4% (1/247) of patients receiving OPDIVO QVANTIG, including a Grade 1 (0.4%) adverse reaction..

单药静脉注射nivolumab治疗的患者中有0.6%（12/1994）发生垂体炎，包括3级（0.2%）和2级（0.3%）。接受OPDIVO QVANTIG治疗的患者中有0.4%（1/247）发生甲状腺炎，包括1级（0.4%）不良反应。。

Hyperthyroidism occurred in 0.8% (2/247) of patients receiving OPDIVO QVANTIG, including Grade 2 (0.4%) adverse reactions. Hypothyroidism occurred in 9% (23/247) of patients receiving OPDIVO QVANTIG, including Grade 2 (5.7%) adverse reactions.

接受OPDIVO QVANTIG治疗的患者中有0.8%（2/247）发生甲状腺功能亢进，包括2级（0.4%）不良反应。接受OPDIVO QVANTIG治疗的患者中有9%（23/247）发生甲状腺功能减退，包括2级（5.7%）不良反应。

Grade 3 diabetes occurred in 0.4% (1/247) of patients receiving OPDIVO QVANTIG.

接受OPDIVO QVANTIG治疗的患者中有0.4%（1/247）发生3级糖尿病。

Immune-Mediated Nephritis with Renal Dysfunction

免疫介导性肾炎伴肾功能不全

OPDIVO QVANTIG can cause immune-mediated nephritis.

OPDIVO QVANTIG可引起免疫介导的肾炎。

Grade 2 immune-mediated nephritis and renal dysfunction occurred in 1.2% (3/247) of patients receiving OPDIVO QVANTIG.

接受OPDIVO QVANTIG治疗的患者中有1.2%（3/247）发生2级免疫介导的肾炎和肾功能不全。

Immune-Mediated Dermatologic Adverse Reactions

免疫介导的皮肤病不良反应

OPDIVO QVANTIG can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens- Johnson Syndrome, toxic epidermal necrolysis (TEN), and DRESS (drug rash with eosinophilia and systemic symptoms), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

OPDIVO QVANTIG可引起免疫介导的皮疹或皮炎。PD-1/PD-L1阻断抗体发生了剥脱性皮炎，包括史蒂文斯-约翰逊综合征，中毒性表皮坏死松解症（TEN）和DRESS（伴有嗜酸性粒细胞增多和全身症状的药疹）。局部润肤剂和/或局部皮质类固醇可能足以治疗轻度至中度非剥脱性皮疹。

Withhold or permanently discontinue OPDIVO QVANTIG depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information)..

根据严重程度，扣留或永久停用OPDIVO QVANTIG（请参阅随附的完整处方信息中的第2节剂量和给药）。。

Immune-mediated rash occurred in 7% (17/247) of patients, including Grade 3 (0.8%) and Grade 2 (2.8%) adverse reactions.

7%（17/247）的患者发生免疫介导的皮疹，包括3级（0.8%）和2级（2.8%）不良反应。

Other Immune-Mediated Adverse Reactions

其他免疫介导的不良反应

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO QVANTIG or intravenous nivolumab as single agent or in combination with chemotherapy or immunotherapy, or were reported with the use of other PD-1/PD-L1 blocking antibodies.

在接受OPDIVO QVANTIG或静脉注射nivolumab作为单一药物或联合化疗或免疫治疗的患者中，或据报道使用其他PD-1/PD-L1阻断抗体的患者中，以下临床显着的免疫介导的不良反应发生率<1%（除非另有说明）。

Severe or fatal cases have been reported for some of these adverse reactions: .

其中一些不良反应报告了严重或致命的病例：。

cardiac/vascular

心脏/血管

: myocarditis, pericarditis, vasculitis;

：心肌炎，心包炎，血管炎；

nervous system

神经系统

: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy;

：脑膜炎，脑炎，脊髓炎和脱髓鞘，肌无力综合征/重症肌无力（包括恶化），格林-巴利综合征，神经麻痹，自身免疫性神经病；

ocular

眼部

: uveitis, iritis, and other ocular inflammatory toxicities can occur;

：可能发生葡萄膜炎，虹膜炎和其他眼部炎症毒性；

gastrointestinal

胃肠道

: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis;

：胰腺炎包括血清淀粉酶和脂肪酶水平升高，胃炎，十二指肠炎；

musculoskeletal and connective tissue

肌肉骨骼和结缔组织

: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica;

：肌炎/多发性肌炎，横纹肌溶解症和相关后遗症，包括肾衰竭，关节炎，风湿性多肌痛；

endocrine

内分泌

: hypoparathyroidism;

：甲状旁腺功能低下；

other (hematologic/immune)

其他（血液学/免疫）

: hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection..

：溶血性贫血、再生障碍性贫血、吞噬性淋巴组织细胞增多症（HLH）、全身炎症反应综合征、组织细胞坏死性淋巴结炎（菊池淋巴结炎）、结节病、免疫性血小板减少性紫癜、实体器官移植排斥反应、其他移植（包括角膜移植）排斥反应。。

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss..

一些眼部IMAR病例可能与视网膜脱离有关。可能会出现各种程度的视力障碍，包括失明。如果葡萄膜炎与其他免疫介导的不良反应一起发生，请考虑Vogt-Koyanagi-Harada样综合征，因为这可能需要用全身皮质类固醇治疗以降低永久性视力丧失的风险。。

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

异基因造血干细胞移植的并发症

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO QVANTIG. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).

在接受OPDIVO QVANTIG治疗之前或之后接受异基因造血干细胞移植（HSCT）的患者可能会发生致命和其他严重并发症。与移植相关的并发症包括超急性移植物抗宿主病（GVHD），急性GVHD，慢性GVHD，降低强度调理后的肝静脉闭塞性疾病（VOD）以及需要类固醇的发热综合征（无确定的感染原因）。

These complications may occur despite intervening therapy between OPDIVO QVANTIG and allogeneic HSCT..

尽管OPDIVO QVANTIG和同种异体HSCT之间进行了干预治疗，但仍可能发生这些并发症。。

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO QVANTIG prior to or after an allogeneic HSCT.

密切关注患者的移植相关并发症证据，并及时干预。考虑在同种异体HSCT之前或之后用OPDIVO QVANTIG治疗的益处与风险。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

Based on its mechanism of action and data from animal studies, OPDIVO QVANTIG can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death.

根据其作用机制和动物研究数据，OPDIVO QVANTIG给孕妇服用时可能会造成胎儿伤害。在动物繁殖研究中，从器官发生开始到分娩，对食蟹猴施用nivolumab会导致流产和早产儿死亡增加。

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO QVANTIG and for 5 months after the last dose..

告知孕妇对胎儿的潜在风险。建议有生殖潜力的女性在使用OPDIVO QVANTIG治疗期间和最后一剂后5个月内使用有效的避孕措施。。

Increased Mortality in Patients with Multiple Myeloma when Nivolumab Is Added to a Thalidomide Analogue and Dexamethasone

当将Nivolumab添加到沙利度胺类似物和地塞米松中时，多发性骨髓瘤患者的死亡率增加

In randomized clinical trials in patients with multiple myeloma, the addition of a PD-1 blocking antibody, including intravenous nivolumab, to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials..

在多发性骨髓瘤患者的随机临床试验中，在沙利度胺类似物加地塞米松中加入PD-1阻断抗体（包括静脉注射nivolumab），这是一种没有PD-1或PD-L1阻断抗体的用途，导致死亡率增加。在对照临床试验之外，不建议使用PD-1或PD-L1阻断抗体联合沙利度胺类似物加地塞米松治疗多发性骨髓瘤患者。。

Lactation

哺乳期

There are no data on the presence of nivolumab or hyaluronidase in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 5 months after the last dose of OPDIVO QVANTIG..

没有关于母乳中存在nivolumab或透明质酸酶，对母乳喂养儿童的影响或对产奶量的影响的数据。由于母乳喂养的孩子可能会产生严重的不良反应，因此建议女性在治疗期间以及服用最后一剂OPDIVO QVANTIG后的5个月内不要母乳喂养。。

Serious Adverse Reactions

严重不良反应

In Checkmate 67T, serious adverse reactions occurred in 28% of patients who received OPDIVO QVANTIG (n=247). Serious adverse reactions in >1% of patients included pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%). Fatal adverse reactions occurred in 3 patients (1.2%) who received OPDIVO QVANTIG and included myocarditis, myositis, and colitis complications.

。>1%的患者出现严重不良反应，包括胸腔积液（1.6%），肺炎（1.6%），高血糖（1.2%），高钾血症（1.2%），出血（1.2%）和腹泻（1.2%）。接受OPDIVO QVANTIG治疗的3例患者（1.2%）发生致命不良反应，包括心肌炎，肌炎和结肠炎并发症。

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving intravenous nivolumab (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving intravenous nivolumab. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving intravenous nivolumab were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

在Checkmate 037中，41%接受静脉注射nivolumab的患者发生严重不良反应（n=268）。42%接受静脉注射nivolumab的患者发生3级和4级不良反应。在接受静脉注射nivolumab的患者中，2%至5%的患者报告的最常见的3级和4级不良反应是腹痛，低钠血症，天冬氨酸转氨酶升高和脂肪酶升高。

In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving intravenous nivolumab (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving intravenous nivolumab. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving intravenous nivolumab were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%).

在Checkmate 066中，36%接受静脉注射nivolumab的患者发生严重不良反应（n=206）。41%接受静脉注射nivolumab的患者发生3级和4级不良反应。接受静脉注射nivolumab的患者中≥2%报告的最常见的3级和4级不良反应是γ-谷氨酰转移酶升高（3.9%）和腹泻（3.4%）。

In Checkmate 067, the most frequent (≥10%) serious adverse reactions in the intravenous nivolumab arm (n=313) were diarrhea (2.2%), colitis (1.9%), and pyrexia (1.0%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the intravenous nivolumab plus intravenous ipilimumab arm (n=313) relative to the intravenous nivolumab arm (n=313).

在Checkmate 067中，静脉注射nivolumab组（n=313）中最常见（≥10%）的严重不良反应是腹泻（2.2%），结肠炎（1.9%）和发热（1.0%）。在Checkmate 067中，严重不良反应（74%和44%），导致永久停药（47%和18%）或给药延迟（58%和36%）的不良反应以及3级或4级不良反应（72%和51%）相对于静脉注射nivolumab组（n=313），静脉注射nivolumab加静脉注射ipilimumab组（n=313）发生频率更高。

The most frequent (≥10%) serio.

最常见的（≥10%）系列。

In Checkmate 816, serious adverse reactions occurred in 30% of patients (n=176) who were treated with intravenous nivolumab in combination with platinum-doublet chemotherapy. Serious adverse reactions in >2% included pneumonia and vomiting. No fatal adverse reactions occurred in patients who received intravenous nivolumab in combination with platinum-doublet chemotherapy.

。>2%的严重不良反应包括肺炎和呕吐。静脉注射nivolumab联合铂类双联化疗的患者未发生致命的不良反应。

In Checkmate 77T, serious adverse reactions occurred in 21% of patients who received intravenous nivolumab in combination with platinum-doublet chemotherapy as neoadjuvant treatment (n=228). The most frequent (≥2%) serious adverse reactions was pneumonia. Fatal adverse reactions occurred in 2.2% of patients, due to cerebrovascular accident, COVID-19 infection, hemoptysis, pneumonia, and pneumonitis (0.4% each).

在Checkmate 77T中，21%接受静脉注射nivolumab联合铂类双联化疗作为新辅助治疗的患者发生严重不良反应（n=228）。最常见（≥2%）的严重不良反应是肺炎。由于脑血管意外，新型冠状病毒感染，咯血，肺炎和肺炎（各0.4%），2.2%的患者发生致命不良反应。

In the adjuvant phase of Checkmate 77T, 22% of patients experienced serious adverse reactions (n=142). The most frequent serious adverse reaction was pneumonitis/ILD (2.8%). One fatal adverse reaction due to COVID-19 occurred. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving intravenous nivolumab (n=418).

在Checkmate 77T的辅助阶段，22%的患者出现严重的不良反应（n=142）。最常见的严重不良反应是肺炎/ILD（2.8%）。发生了一种由COVID-19引起的致命不良反应。在Checkmate 017和057中，46%接受静脉注射nivolumab（n=418）的患者发生严重不良反应。

The most frequent serious adverse reactions reported in ≥2% of patients receiving intravenous nivolumab were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient).

接受静脉注射nivolumab的患者中≥2%报告的最常见严重不良反应是肺炎，肺栓塞，呼吸困难，发热，胸腔积液，肺炎和呼吸衰竭。在Checkmate 057中，发生了致命的不良反应；其中包括感染事件（7例，包括1例吉罗维肺孢子虫肺炎），肺栓塞（4例）和边缘脑炎（1例）。

In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving intravenous nivolumab plus intravenous ipilimumab (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were dia.

在Checkmate 214中，59%接受静脉注射nivolumab加静脉注射ipilimumab（n=547）的患者发生严重不良反应。在≥2%的患者中报告的最常见的严重不良反应是dia。

Common Adverse Reactions

常见不良反应

In Checkmate 67T, the most common adverse reactions (≥10%) in patients treated with OPDIVO QVANTIG (n=247) were musculoskeletal pain (31%), fatigue (20%), pruritus (16%), rash (15%), hypothyroidism (12%), diarrhea (11%), cough (11%), and abdominal pain (10%). In Checkmate 037, the most common adverse reaction (≥20%) reported with intravenous nivolumab (n=268) was rash (21%).

在Checkmate 67T中，使用OPDIVO QVANTIG（n=247）治疗的患者最常见的不良反应（≥10%）是肌肉骨骼疼痛（31%），疲劳（20%），瘙痒（16%），皮疹（15%），甲状腺功能减退（12%），腹泻（11%），咳嗽（11%）和腹痛（10%）。在Checkmate 037中，静脉注射nivolumab（n=268）报告的最常见不良反应（≥20%）是皮疹（21%）。

In Checkmate 066, the most common adverse reactions (≥20%) reported with intravenous nivolumab (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the intravenous nivolumab arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

。在Checkmate 067中，静脉注射nivolumab组（n=313）最常见（≥20%）的不良反应是疲劳（59%），皮疹（40%），肌肉骨骼疼痛（42%），腹泻（36%），恶心（30%），咳嗽（28%），瘙痒（27%），上呼吸道感染（22%），食欲下降（22%），头痛（22%），便秘（21%），关节痛（21%）和呕吐（20%）。

In Checkmate 067, the most common (≥20%) adverse reactions in the intravenous nivolumab plus intravenous ipilimumab arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%)..

在Checkmate 067中，静脉注射nivolumab加静脉注射ipilimumab组（n=313）最常见（≥20%）的不良反应是疲劳（62%），腹泻（54%），皮疹（53%），恶心（44%），发热（40%），瘙痒（39%），肌肉骨骼疼痛（32%），呕吐（31%），食欲下降（29%），咳嗽（27%），头痛（26%），呼吸困难（24%），上呼吸道感染（23%），关节痛（21%）和转氨酶升高（25%）。。

In Checkmate 816, the most common (>20%) adverse reactions in the intravenous nivolumab plus chemotherapy arm (n=176) were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%).In Checkmate 77T, the most common adverse reactions (reported in ≥20%) in patients receiving intravenous nivolumab in combination with chemotherapy (n= 228) were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%).In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving intravenous nivolumab (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

在Checkmate 816中，静脉注射nivolumab加化疗组（n=176）最常见（>20%）的不良反应是恶心（38%），便秘（34%），疲劳（26%），食欲下降（20%）和皮疹（20%）。在Checkmate 77T中，接受静脉注射nivolumab联合化疗（n=228）的患者最常见的不良反应（报告≥20%）是贫血（39.5%），便秘（32.0%），恶心（28.9%），疲劳（28.1%），脱发（25.9%）和咳嗽（21.9%）。在Checkmate 017和057中，接受静脉注射nivolumab（n=418）的患者最常见的不良反应（≥20%）是疲劳，肌肉骨骼疼痛，咳嗽，呼吸困难和食欲下降。

In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with intravenous nivolumab plus intravenous ipilimumab (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%).

在Checkmate 214中，静脉注射nivolumab加静脉注射ipilimumab（n=547）治疗的患者最常见的不良反应（≥20%）是疲劳（58%），皮疹（39%），腹泻（38%），肌肉骨骼疼痛（37%），瘙痒（33%），恶心（30%），咳嗽（28%），发热（25%），关节痛（23%），食欲下降（21%），呼吸困难（20%）和呕吐（20%）。

In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving intravenous nivolumab and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%).

在Checkmate 9ER中，接受静脉注射nivolumab和cabozantinib（n=320）的患者最常见的不良反应（≥20%）是腹泻（64%），疲劳（51%），肝毒性（44%），掌底红细胞感觉异常综合征（40%），口腔炎（37%），皮疹（36%），高血压（36%），甲状腺功能减退（34%），肌肉骨骼疼痛（33%），食欲下降（28%），恶心（27%），味觉障碍（24%），腹痛（22%），咳嗽（20%）和上呼吸道感染（20%）。

In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving intravenous nivolumab (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation.

在Checkmate 025中，接受静脉注射nivolumab（n=406）与依维莫司（n=397）的患者报告的最常见不良反应（≥20%）是疲劳（56%比57%），咳嗽（34%比38%），恶心（28%比29%），皮疹（28%比36%），呼吸困难（27%比31%），腹泻（25%比32%），便秘。

Surgery Related Adverse Reactions

手术相关不良反应

In Checkmate 77T, 5.3% (n=12) of the intravenous nivolumab-treated patients who received neoadjuvant treatment, did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery in intravenous nivolumab-treated patients were cerebrovascular accident, pneumonia, and colitis/diarrhea (2 patients each) and acute coronary syndrome, myocarditis, hemoptysis, pneumonitis, COVID-19, and myositis (1 patient each)..

在Checkmate 77T中，接受新辅助治疗的静脉注射nivolumab治疗的患者中有5.3%（n=12）由于不良反应而未接受手术。导致静脉注射nivolumab治疗患者取消手术的不良反应包括脑血管意外，肺炎和结肠炎/腹泻（各2例）以及急性冠状动脉综合征，心肌炎，咯血，肺炎，COVID-19和肌炎（各1例）。。

Please see U.S. Full Prescribing Information for

请参阅美国完整处方信息

OPDIVO QVANTIG.

选择数量。

INDICATIONS

适应症

OPDIVO®

选择®

(nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

（nivolumab）作为单一药物，适用于治疗12岁及以上无法切除或转移性黑色素瘤的成人和儿科患者。

OPDIVO®

选择®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

（ipilimumab），适用于治疗12岁及以上的成人和儿科患者，患有不可切除或转移性黑色素瘤。

OPDIVO®

选择®

is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.

适用于12岁及以上完全切除IIB期，IIC期，III期或IV期黑色素瘤的成人和儿科患者的辅助治疗。

OPDIVO®

OPDIVO®

(nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

（nivolumab）联合铂类双联化疗被认为是可切除（肿瘤≥4 cm或淋巴结阳性）非小细胞肺癌（NSCLC）成年患者的新辅助治疗。

OPDIVO®

选择®

(nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO®.

（nivolumab）联合铂类双联化疗，适用于可切除（肿瘤≥4 cm或淋巴结阳性）非小细胞肺癌（NSCLC）且无已知表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排的成年患者的新辅助治疗，其次是单药OPDIVO®。

as adjuvant treatment after surgery.

作为手术后的辅助治疗。

OPDIVO®

选择®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

（ipilimumab）适用于转移性非小细胞肺癌（NSCLC）成年患者的一线治疗，其肿瘤表达PD-L1（≥1%），通过FDA批准的测试确定，没有EGFR或ALK基因组肿瘤畸变。

OPDIVO®

OPDIVO®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

（ipilimumab）和2个周期的铂双联化疗，适用于转移性或复发性非小细胞肺癌（NSCLC）成年患者的一线治疗，无EGFR或ALK基因组肿瘤畸变。

OPDIVO®

选择®

(nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO..

（nivolumab）适用于治疗成年转移性非小细胞肺癌（NSCLC）患者，铂类化疗时或化疗后进展。患有EGFR或ALK基因组肿瘤畸变的患者在接受OPDIVO之前，应在FDA批准的这些畸变治疗中取得疾病进展。。

OPDIVO®

OPDIVO®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

（ipilimumab）适用于无法切除的恶性胸膜间皮瘤（MPM）成年患者的一线治疗。

OPDIVO®

选择®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

（ipilimumab）适用于中危或低危晚期肾细胞癌（RCC）成年患者的一线治疗。

OPDIVO®

选择®

(nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

（nivolumab）与cabozantinib联合用于成人晚期肾细胞癌（RCC）患者的一线治疗。

OPDIVO®

选择®

(nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

（nivolumab）适用于治疗先前接受过抗血管生成治疗的成年晚期肾细胞癌（RCC）患者。

OPDIVO®

选择®

(nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

（nivolumab）适用于治疗复发或转移性头颈部鳞状细胞癌（SCCHN）的成年患者，其在铂类治疗时或之后疾病进展。

OPDIVO®

OPDIVO®

(nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy..

（nivolumab）适用于治疗局部晚期或转移性尿路上皮癌的成年患者，这些患者在含铂化疗期间或之后有疾病进展，或者在新辅助治疗或含铂化疗辅助治疗后12个月内有疾病进展。。

OPDIVO®

选择®

(nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

（nivolumab）作为单一药物，适用于成人尿路上皮癌（UC）患者的辅助治疗，这些患者在接受UC根治性切除术后复发风险很高。

OPDIVO®

OPDIVO®

(nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.

（nivolumab）联合顺铂和吉西他滨被认为是成人不可切除或转移性尿路上皮癌患者的一线治疗方法。

OPDIVO®

OPDIVO®

(nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

（nivolumab）用于治疗先前氟嘧啶和铂类化疗后无法切除的晚期，复发或转移性食管鳞状细胞癌（ESCC）的成年患者。

OPDIVO®

选择®

(nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

（nivolumab）适用于接受新辅助放化疗（CRT）的成年患者中完全切除的食管或胃食管交界癌伴残留病理性疾病的辅助治疗。

OPDIVO®

选择®

(nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

（nivolumab）与含氟嘧啶和铂的化疗联合使用，适用于无法切除的晚期或转移性食管鳞状细胞癌（ESCC）成年患者的一线治疗。

OPDIVO®

选择®

(nivolumab), in combination with YERVOY®

（nivolumab），与YERVOY®结合使用

(ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

。

OPDIVO®

选择®

(nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

。

IMPORTANT SAFETY INFORMATION

重要安全信息

Severe and Fatal Immune-Mediated Adverse Reactions

严重和致命的免疫介导的不良反应

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune- mediated adverse reactions.

本文列出的免疫介导的不良反应可能不包括所有可能的严重和致命的免疫介导的不良反应。

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY.

免疫介导的不良反应可能严重或致命，可能发生在任何器官系统或组织中。虽然免疫介导的不良反应通常在治疗期间表现出来，但它们也可能在停用OPDIVO或YERVOY后发生。早期识别和管理对于确保OPDIVO和YERVOY的安全使用至关重要。

Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY.

监测可能是潜在免疫介导的不良反应的临床表现的体征和症状。评估临床化学物质，包括肝酶，肌酐，促肾上腺皮质激素（ACTH）水平和甲状腺功能，在基线和OPDIVO治疗期间以及每次服用YERVOY之前定期进行评估。

In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate..

在疑似免疫介导的不良反应的情况下，启动适当的检查以排除其他病因，包括感染。及时进行医疗管理，包括适当的专业咨询。。

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less.

根据严重程度扣留或永久停用OPDIVO和YERVOY（请参阅随附的完整处方信息中的第2节剂量和给药）。。

Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below..

在改善至1级或更低级别后，开始逐渐减少皮质类固醇，并在至少1个月内继续逐渐减少。考虑在免疫介导的不良反应不能用皮质类固醇治疗控制的患者中使用其他全身免疫抑制剂。下面讨论不一定需要全身类固醇（例如内分泌病和皮肤病反应）的不良反应的毒性管理指南。。

Immune-Mediated Pneumonitis

免疫介导性肺炎

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune- mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%).

OPDIVO和YERVOY可引起免疫介导的肺炎。先前接受过胸部放疗的患者肺炎的发生率较高。在接受OPDIVO单药治疗的患者中，免疫介导的肺炎发生率为3.1%（61/1994），包括4级（<0.1%），3级（0.9%）和2级（2.1%）。

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune- mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune- mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%).

在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，7%（31/456）的患者发生免疫介导的肺炎，包括4级（0.2%），3级（2.0%）和2级（4.4%）。在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，免疫介导的肺炎发生率为3.9%（26/666），包括3级（1.4%）和2级（2.6%）。

In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune- mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis..

在每2周接受OPDIVO 3 mg/kg，每6周接受YERVOY 1 mg/kg的NSCLC患者中，9%（50/576）的患者发生免疫介导的肺炎，包括4级（0.5%），3级（3.5%）和2级（4.0%）。四名患者（0.7%）死于肺炎。。

Immune-Mediated Colitis

免疫介导的结肠炎

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

OPDIVO和YERVOY可引起免疫介导的结肠炎，这可能是致命的。结肠炎定义中的常见症状是腹泻。据报道，皮质类固醇难治性免疫介导性结肠炎患者的巨细胞病毒（CMV）感染/再激活。在皮质类固醇难治性结肠炎的情况下，考虑重复感染性检查以排除其他病因。

In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%).

在接受OPDIVO单药治疗的患者中，2.9%（58/1994）的患者发生免疫介导的结肠炎，包括3级（1.7%）和2级（1%）。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，25%（115/456）的患者发生免疫介导的结肠炎，包括4级（0.4%），3级（14%）和2级（8%）。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，9%（60/666）的患者发生免疫介导的结肠炎，包括3级（4.4%）和2级（3.7%）。。

Immune-Mediated Hepatitis and Hepatotoxicity

免疫介导的肝炎和肝毒性

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune- mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%).

OPDIVO和YERVOY可引起免疫介导的肝炎。在接受OPDIVO单药治疗的患者中，1.8%（35/1994）的患者发生免疫介导的肝炎，包括4级（0.2%），3级（1.3%）和2级（0.4%）。。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，7%（48/666）的患者发生免疫介导的肝炎，包括4级（1.2%），3级（4.9%）和2级（0.4%）。。

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients..

与单独使用OPDIVO相比，OPDIVO联合cabozantinib可引起肝毒性，3级和4级ALT和AST升高的频率更高。与作为单一药物给药时相比，考虑更频繁地监测肝酶。在接受OPDIVO和cabozantinib治疗的患者中，11%的患者出现3级和4级ALT或AST升高。。

Immune-Mediated Endocrinopathies

免疫介导的内分泌病

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

OPDIVO和YERVOY可引起原发性或继发性肾上腺皮质功能不全，免疫介导的垂体炎，免疫介导的甲状腺疾病和1型糖尿病，并可伴有糖尿病酮症酸中毒。根据严重程度扣留OPDIVO和YERVOY（请参阅随附的完整处方信息中的第2节剂量和给药）。

For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated.

对于2级或更高级别的肾上腺功能不全，开始对症治疗，包括临床指示的激素替代。垂体炎可出现与肿块效应相关的急性症状，例如头痛，畏光或视野缺损。垂体炎可引起垂体功能减退；根据临床指示开始激素替代。

Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated..

甲状腺炎可伴有或不伴有内分泌病。甲状腺功能减退症可继发甲状腺功能亢进症；根据临床指示开始激素替代或医疗管理。监测患者的高血糖或其他糖尿病体征和症状；根据临床指示开始胰岛素治疗。。

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%).

在接受OPDIVO单药治疗的患者中，肾上腺功能不全发生率为1%（20/1994），包括3级（0.4%）和2级（0.6%）。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，肾上腺功能不全发生率为8%（35/456），包括4级（0.2%），3级（2.4%）和2级（4.2%）。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，7%（48/666）的患者发生肾上腺功能不全，包括4级（0.3%），3级（2.5%）和2级（4.1%）。在接受OPDIVO和cabozantinib治疗的患者中，肾上腺功能不全发生率为4.7%（15/320），包括3级（2.2%）和2级（1.9%）。。

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).

在接受OPDIVO单药治疗的患者中，0.6%（12/1994）的患者发生垂体炎，包括3级（0.2%）和2级（0.3%）。

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%)..

在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，垂体炎发生率为9%（42/456），包括3级（2.4%）和2级（6%）。在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，4.4%（29/666）的患者发生垂体炎，包括4级（0.3%），3级（2.4%）和2级（0.9%）。。

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

。在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，2.7%（22/666）的患者发生甲状腺炎，包括3级（4.5%）和2级（2.2%）。

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%).

在接受OPDIVO单药治疗的患者中，甲状腺功能亢进发生率为2.7%（54/1994），包括3级（<0.1%）和2级（1.2%）。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，9%（42/456）的患者发生甲状腺功能亢进，包括3级（0.9%）和2级（4.2%）。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，12%（80/666）的患者发生甲状腺功能亢进，包括3级（0.6%）和2级（4.5%）。。

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%).

在接受OPDIVO单药治疗的患者中，甲状腺功能减退发生率为8%（163/1994），包括3级（0.2%）和2级（4.8%）。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，甲状腺功能减退发生率为20%（91/456），包括3级（0.4%）和2级（11%）。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，18%（122/666）的患者发生甲状腺功能减退，包括3级（0.6%）和2级（11%）。。

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%)..

。在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，2.7%（15/666）的患者发生糖尿病，包括4级（0.6%），3级（0.3%）和2级（0.9%）。。

Immune-Mediated Nephritis with Renal Dysfunction

免疫介导性肾炎伴肾功能不全

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%)..

。在接受OPDIVO单药治疗的患者中，1.2%（23/1994）的患者发生免疫介导的肾炎和肾功能不全，包括4级（<0.1%），3级（0.5%）和2级（0.6%）。在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，4.1%（27/666）的患者发生免疫介导的肾功能不全性肾炎，包括4级（0.6%），3级（1.1%）和2级（2.2%）。。

Immune-Mediated Dermatologic Adverse Reactions

免疫介导的皮肤病不良反应

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes..

OPDIVO可引起免疫介导的皮疹或皮炎。PD-1/PD-L1阻断抗体发生了剥脱性皮炎，包括史蒂文斯-约翰逊综合征（SJS），中毒性表皮坏死松解症（TEN）和伴有嗜酸性粒细胞增多和全身症状的药疹（DRESS）。局部润肤剂和/或局部皮质类固醇可能足以治疗轻度至中度非风湿性皮疹。。

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

YERVOY可引起免疫介导的皮疹或皮炎，包括大疱性和剥脱性皮炎，SJS，TEN和DRESS。局部润肤剂和/或局部皮质类固醇可能足以治疗轻度至中度非大疱性/剥脱性皮疹。

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

根据严重程度，扣留或永久停用OPDIVO和YERVOY（请参阅随附的完整处方信息中的第2节剂量和给药）。

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%).

在接受OPDIVO单药治疗的患者中，9%（171/1994）的患者发生免疫介导的皮疹，包括3级（1.1%）和2级（2.2%）。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的患者中，28%（127/456）的患者发生免疫介导的皮疹，包括3级（4.8%）和2级（10%）。

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%)..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的患者中，16%（108/666）的患者发生免疫介导的皮疹，包括3级（3.5%）和2级（4.2%）。。

Other Immune-Mediated Adverse Reactions

其他免疫介导的不良反应

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies.

在接受OPDIVO单药治疗或OPDIVO联合YERVOY治疗或报告使用其他PD-1/PD-L1阻断抗体的患者中，以下临床显着的免疫介导的不良反应发生率<1%（除非另有说明）。

Severe or fatal cases have been reported for some of these adverse reactions: .

其中一些不良反应报告了严重或致命的病例：。

cardiac/vascular:

心脏/血管：

myocarditis, pericarditis, vasculitis;

心肌炎，心包炎，血管炎；

nervous system:

神经系统：

meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy;

脑膜炎，脑炎，脊髓炎和脱髓鞘，肌无力综合征/重症肌无力（包括恶化），格林-巴利综合征，神经麻痹，自身免疫性神经病；

ocular:

眼部：

uveitis, iritis, and other ocular inflammatory toxicities can occur;

可能发生葡萄膜炎，虹膜炎和其他眼部炎症毒性；

gastrointestinal:

胃肠道：

pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis;

胰腺炎包括血清淀粉酶和脂肪酶水平升高，胃炎，十二指肠炎；

musculoskeletal and connective tissue:

肌肉骨骼和结缔组织：

myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica;

肌炎/多发性肌炎，横纹肌溶解症和相关后遗症，包括肾衰竭，关节炎，风湿性多肌痛；

endocrine:

内分泌：

hypoparathyroidism;

；

other (hematologic/immune):

其他（血液学/免疫）：

hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection..

溶血性贫血、再生障碍性贫血、吞噬性淋巴组织细胞增多症（HLH）、全身炎症反应综合征、组织细胞坏死性淋巴结炎（菊池淋巴结炎）、结节病、免疫性血小板减少性紫癜、实体器官移植排斥反应、其他移植（包括角膜移植）排斥反应。。

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: .

除了上面列出的免疫介导的不良反应外，在YERVOY单一疗法或与OPDIVO联合的临床试验中，除非另有说明，否则以下临床上显着的免疫介导的不良反应（一些致命的结果）发生在1%以下的患者中：。

nervous system:

神经系统：

autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction;

自身免疫性神经病（2%），肌无力综合征/重症肌无力，运动功能障碍；

cardiovascular:

心血管疾病：

angiopathy, temporal arteritis;

血管病，颞动脉炎；

ocular:

眼部：

blepharitis, episcleritis, orbital myositis, scleritis;

睑缘炎，巩膜炎，眼眶肌炎，巩膜炎；

gastrointestinal:

胃肠道：

pancreatitis (1.3%);

胰腺炎（1.3%）；

other (hematologic/immune):

其他（血液学/免疫）：

conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

结膜炎，血细胞减少症（2.5%），嗜酸性粒细胞增多症（2.1%），多形性红斑，超敏性血管炎，神经感觉性视力减退，牛皮癣。

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss..

一些眼部IMAR病例可能与视网膜脱离有关。可能会出现各种程度的视力障碍，包括失明。如果葡萄膜炎与其他免疫介导的不良反应一起发生，请考虑在接受OPDIVO和YERVOY治疗的患者中观察到的Vogt-Koyanagi-Harada样综合征，因为这可能需要使用全身皮质类固醇治疗以降低永久性视力丧失的风险。。

Infusion-Related Reactions

输液相关反应

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions.

OPDIVO和YERVOY可引起严重的输液相关反应。对于严重（3级）或危及生命（4级）输注相关反应的患者，停用OPDIVO和YERVOY。轻度（1级）或中度（2级）输液相关反应患者中断或减慢输液速度。

In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30- minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively.

在接受OPDIVO单药治疗60分钟输注的患者中，6.4%（127/1994）的患者发生了输注相关反应。在一项单独的试验中，患者接受OPDIVO单药治疗60分钟输注或30分钟输注，分别有2.2%（8/368）和2.7%（10/369）的患者发生输注相关反应。

Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients.

此外，分别有0.5%（2/368）和1.4%（5/369）的患者在输注后48小时内出现不良反应，导致剂量延迟，永久停药或停用OPDIVO。在每3周接受OPDIVO 1 mg/kg和YERVOY 3 mg/kg的黑色素瘤患者中，2.5%（10/407）的患者发生了输注相关反应。

In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 5.1% (28/547) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients..

在每3周接受OPDIVO 3 mg/kg和YERVOY 1 mg/kg的RCC患者中，5.1%（28/547）的患者发生了输注相关反应。MPM患者每2周接受OPDIVO 3 mg/kg，每6周接受YERVOY 1 mg/kg，12%（37/300）的患者发生输注相关反应。。

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

异基因造血干细胞移植的并发症

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).

在接受OPDIVO或YERVOY治疗之前或之后接受异基因造血干细胞移植（HSCT）的患者可能会发生致命和其他严重并发症。与移植相关的并发症包括超急性移植物抗宿主病（GVHD），急性GVHD，慢性GVHD，降低强度调理后的肝静脉闭塞性疾病（VOD）以及需要类固醇的发热综合征（无确定的感染原因）。

These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT..

尽管OPDIVO或YERVOY与同种异体HSCT之间进行了干预治疗，但仍可能发生这些并发症。。

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

密切关注患者的移植相关并发症证据，并及时干预。考虑在同种异体HSCT之前或之后用OPDIVO和YERVOY治疗的益处与风险。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus.

根据其作用机制和动物研究的结果，OPDIVO和YERVOY给孕妇服用时会造成胎儿伤害。YERVOY在妊娠中期和晚期的影响可能更大。告知孕妇对胎儿的潜在风险。

Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose..

。。

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

当将OPDIVO添加到沙利度胺类似物和地塞米松中时，多发性骨髓瘤患者的死亡率增加

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials..

在多发性骨髓瘤患者的随机临床试验中，在沙利度胺类似物加地塞米松中加入OPDIVO导致死亡率增加。在对照临床试验之外，不建议使用PD-1或PD-L1阻断抗体联合沙利度胺类似物加地塞米松治疗多发性骨髓瘤患者。。

Lactation

哺乳期

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose..

没有关于母乳中存在OPDIVO或YERVOY，对母乳喂养的孩子的影响或对牛奶生产的影响的数据。由于母乳喂养的儿童可能会产生严重的不良反应，因此建议女性在治疗期间和最后一次服用后的5个月内不要母乳喂养。。

Serious Adverse Reactions

严重不良反应

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

在Checkmate 037中，41%接受OPDIVO治疗的患者发生严重不良反应（n=268）。。在接受OPDIVO治疗的患者中，2%至5%的患者报告的最常见的3级和4级不良反应是腹痛，低钠血症，天冬氨酸转氨酶升高和脂肪酶升高。

In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%).

在Checkmate 066中，36%接受OPDIVO治疗的患者发生严重不良反应（n=206）。41%接受OPDIVO治疗的患者发生3级和4级不良反应。在接受OPDIVO治疗的患者中，≥2%的患者报告的最常见的3级和4级不良反应是γ-谷氨酰转移酶升高（3.9%）和腹泻（3.4%）。

In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).

在Checkmate 067中，严重不良反应（74%和44%），导致永久停药（47%和18%）或给药延迟（58%和36%）的不良反应以及3级或4级不良反应（72%和51%）在OPDIVO加YERVOY组（n=313）中相对于OPDIVO组（n=313）更频繁地发生。

The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452).

OPDIVO加YERVOY组和OPDIVO组最常见（≥10%）的严重不良反应分别为腹泻（13%和2.2%），结肠炎（10%和1.9%）和发热（10%和1.0%）。在Checkmate 238中，接受OPDIVO治疗的患者中有18%发生严重不良反应（n=452）。25%的OPDIVO治疗患者发生3级或4级不良反应（n=452）。

The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Checkmate 816, serious adverse reactions occurred in 30% of patients (n=176) who were treated with OPDIVO in combination with platinum-doublet chemotherapy.

在≥2%的OPDIVO治疗患者中报告的最常见的3级和4级不良反应是腹泻以及脂肪酶和淀粉酶升高。在Checkmate 816中，接受OPDIVO联合铂类双联化疗的患者中有30%（n=176）发生严重不良反应。

Serious adverse reactions in >2% included pneumoni.

超过2%的严重不良反应包括肺炎。

Pneumocystis jirovecii

耶氏肺孢子虫

pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism.

肺炎），肺栓塞（4例）和边缘脑炎（1例）。在Checkmate 743中，54%接受OPDIVO加YERVOY治疗的患者发生严重不良反应。≥2%的患者报告的最常见的严重不良反应是肺炎，发热，腹泻，肺炎，胸腔积液，呼吸困难，急性肾损伤，输液相关反应，肌肉骨骼疼痛和肺栓塞。

Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis.

致命的不良反应发生在4例（1.3%）患者中，包括肺炎，急性心力衰竭，败血症和脑炎。在Checkmate 214中，59%接受OPDIVO加YERVOY治疗的患者发生严重不良反应（n=547）。在≥2%的患者中报告的最常见的严重不良反应是腹泻，发热，肺炎，肺炎，垂体炎，急性肾损伤，呼吸困难，肾上腺功能不全和结肠炎。

In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients.

在Checkmate 9ER中，接受OPDIVO和cabozantinib治疗的患者中有48%发生严重不良反应（n=320）。在≥2%的患者中报告的最常见的严重不良反应是腹泻，肺炎，肺炎，肺栓塞，尿路感染和低钠血症。3例（0.9%）患者发生致命的肠道穿孔。

In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236).

在Checkmate 025中，接受OPDIVO治疗的患者中有47%发生严重不良反应（n=406）。在≥2%的患者中报告的最常见的严重不良反应是急性肾损伤，胸腔积液，肺炎，腹泻和高钙血症。在Checkmate 141中，接受OPDIVO治疗的患者中有49%发生严重不良反应（n=236）。

The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, se.

在接受OPDIVO治疗的患者中，≥2%的患者报告的最常见的严重不良反应是肺炎，呼吸困难，呼吸衰竭，呼吸道感染和败血症。在Checkmate 275，se。

Common Adverse Reactions

常见不良反应

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%).

在Checkmate 037中，OPDIVO（n=268）报告的最常见不良反应（≥20%）是皮疹（21%）。在Checkmate 066中，OPDIVO（n=206）与达卡巴嗪（n=205）报告的最常见不良反应（≥20%）是疲劳（49%比39%），肌肉骨骼疼痛（32%比25%），皮疹（28%比12%）和瘙痒（23%比12%）。

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%).

在Checkmate 067中，OPDIVO加YERVOY组（n=313）最常见（≥20%）的不良反应是疲劳（62%），腹泻（54%），皮疹（53%），恶心（44%），发热（40%），瘙痒（39%），肌肉骨骼疼痛（32%），呕吐（31%），食欲下降（29%），咳嗽（27%），头痛（26%），呼吸困难（24%），上呼吸道感染（23%），关节痛（21%）和转氨酶升高（25%）。

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

在Checkmate 067中，OPDIVO组（n=313）最常见（≥20%）的不良反应是疲劳（59%），皮疹（40%），肌肉骨骼疼痛（42%），腹泻（36%），恶心（30%），咳嗽（28%），瘙痒（27%），上呼吸道感染（22%），食欲下降（22%），头痛（22%），便秘（21%），关节痛（21%）和呕吐（20%）。

In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%).

在Checkmate 238中，OPDIVO治疗患者（n=452）与ipilimumab治疗患者（n=453）报告的最常见不良反应（≥20%）是疲劳（57%比55%），腹泻（37%比55%），皮疹（35%比47%），肌肉骨骼疼痛（32%比27%），瘙痒（28%比37%），头痛（23%比31%），恶心（23%比28%），上呼吸道感染（22%比15%）和腹痛（21%比23%）。

The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Checkmate 816, the most common (>20%) adverse reactions in the OPDIVO plus chemotherapy arm (n=176) were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%).

最常见的免疫介导的不良反应是皮疹（16%），腹泻/结肠炎（6%）和肝炎（3%）。在Checkmate 816中，OPDIVO加化疗组（n=176）最常见（>20%）的不良反应是恶心（38%），便秘（34%），疲劳（26%），食欲下降（20%）和皮疹（20%）。

In Checkmate 77T, the most common adve.

在Checkmate 77T中，最常见的广告。

Surgery Related Adverse Reactions

手术相关不良反应

In Checkmate 77T, 5.3% (n=12) of the OPDIVO-treated patients who received neoadjuvant treatment, did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery in OPDIVO- treated patients were cerebrovascular accident, pneumonia, and colitis/diarrhea (2 patients each) and acute coronary syndrome, myocarditis, hemoptysis, pneumonitis, COVID-19, and myositis (1 patient each)..

在Checkmate 77T中，接受新辅助治疗的OPDIVO治疗患者中有5.3%（n=12）由于不良反应而未接受手术。导致OPDIVO治疗患者取消手术的不良反应包括脑血管意外，肺炎和结肠炎/腹泻（各2例）以及急性冠状动脉综合征，心肌炎，咯血，肺炎，COVID-19和肌炎（各1例）。。

Please see U.S. Full Prescribing Information for

请参阅美国完整处方信息

OPDIVO

选择

and

和

YERVOY

耶尔沃伊

Bristol Myers Squibb: Creating a Better Future for People with Cancer

百时美施贵宝：为癌症患者创造更美好的未来

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus.

百时美施贵宝的灵感来自一个单一的愿景——通过科学改变患者的生活。该公司癌症研究的目标是提供药物，为每位患者提供更好、更健康的生活，并使治愈成为可能。百时美施贵宝（Bristol-Myers Squibb）的研究人员正在探索个性化医学的新前沿，并通过创新的数字平台，将数据转化为见解，从而提高他们的关注度。

Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle..

对因果人类生物学的深刻理解、尖端能力和差异化研究平台使该公司能够从各个角度处理癌症。。

Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future..

癌症可以无情地影响患者生活的许多方面，百时美施贵宝致力于采取行动解决护理的各个方面，从诊断到生存。作为癌症治疗领域的领导者，百时美施贵宝正在努力让所有癌症患者拥有更好的未来。。

About Bristol Myers Squibb’s Patient Access Support

关于百时美施贵宝的患者访问支持

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

百时美施贵宝仍然致力于提供帮助，以便需要我们药物的癌症患者能够获得药物并加快治疗时间。

BMS Access Support®

, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients.

百时美施贵宝患者获取和报销计划旨在帮助适当的患者在治疗过程中启动和维持BMS药物的获取。BMS访问支持为符合条件的商业保险患者提供福利调查、事先授权援助以及共同支付援助。

More information about our access and reimbursement support can be obtained by calling BMS Access Support .

有关我们的访问和报销支持的更多信息，请致电BMS访问支持。

at 1-800-861-0048 or by visiting

拨打1-800-861-0048或访问

www.bmsaccesssupport.com.

www.bmsaccesssupport.com。

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

关于百时美施贵宝和小野制药的合作

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize

2011年，通过与小野制药公司的合作协议，百时美施贵宝扩大了其开发和商业化的领土权利

Opdivo

奇妙

globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan..

在全球范围内，除了日本、韩国和台湾，小野当时保留了该建筑的所有权利。2014年7月23日，小野和百时美施贵宝进一步扩大了公司的战略合作协议，共同开发和商业化多种免疫疗法，作为单一药物和联合方案，用于日本、韩国和台湾的癌症患者。。

About Bristol Myers Squibb

关于百时美施贵宝

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at

。有关百时美施贵宝的更多信息，请访问

BMS.com

BMS.com

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Cautionary Statement Regarding Forward-Looking Statements

关于前瞻性声明的警示声明

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements.

本新闻稿包含1995年《私人证券诉讼改革法案》所指的“前瞻性声明”，其中涉及药品的研究、开发和商业化。。

Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements.

此类前瞻性陈述基于对我们未来财务业绩、目标、计划和目标的当前预期和预测，涉及固有风险、假设和不确定性，包括可能在未来几年延迟、转移或改变其中任何一项的内部或外部因素，这些因素难以预测，可能超出我们的控制范围，并可能导致我们未来的财务业绩、目标、计划和目标与报表中表达或暗示的财务业绩、目标、计划和目标存在重大差异。

These risks, assumptions, uncertainties and other factors include, among others, whether Opdivo Qvantig™ .

这些风险、假设、不确定性和其他因素包括Opdivo Qvantig™是否存在。

(nivolumab and hyaluronidase-nvhy)

for the indications described in this release will be commercially successful, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of Opdivo Qvantig for such indications described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials..

对于本版本中描述的适应症将在商业上取得成功，任何营销批准（如果获得批准）可能对其使用有重大限制，并且Opdivo Qvantig对本版本中描述的此类适应症的持续批准可能取决于验证性试验中临床益处的验证和描述。。

No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission.

不能保证前瞻性声明。本新闻稿中的前瞻性陈述应与影响百时美施贵宝业务和市场的许多风险和不确定性一起进行评估，特别是在百时美施贵宝截至2023年12月31日的年度报告10-K表中的警示声明和风险因素讨论中确定的风险和不确定性，以及我们随后的10-Q表季度报告、8-K表当前报告以及向证券交易委员会提交的其他文件中更新的风险和不确定性。

The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise..

本文件中包含的前瞻性声明仅在本文件日期做出，除非适用法律另有要求，百时美施贵宝没有义务公开更新或修改任何前瞻性声明，无论是由于新信息、未来事件、情况变化还是其他原因。。

References

参考文献

Opdivo Qvantig

任意数量

Prescribing Information.

处方信息。

Opdivo Qvantig

Opdivo Qvantig

U.S. Product Information. Last updated: December 2024. Princeton, NJ: Bristol Myers Squibb Company.

U、 。上次更新时间：2024年12月。新泽西州普林斯顿：百时美施贵宝公司。

Opdivo

Opdivo

Prescribing Information.

处方信息。

Opdivo

奇妙

U.S. Product Information. Last updated: October 2024. Princeton, NJ: Bristol Myers Squibb Company.

U、 。上次更新时间：2024年10月。新泽西州普林斯顿：百时美施贵宝公司。

Albiges L, Bourlon MT, Chacón M, et al. Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

Albiges L，Bourlon MT，Chacón M等。皮下注射与静脉注射nivolumab治疗肾细胞癌。

Ann Oncol

肿瘤学年鉴

. 2024 Sep 15:S0923-7534(24)03996-6.

2024年9月15日：S0923-7534（24）03996-6。

Albiges L, Bourlon MT, Chacón M, et al. Subcutaneous versus intravenous nivolumab for renal cell carcinoma (Supplementary Data).

。

Ann Oncol

肿瘤学年鉴

. 2024 Sep 15:S0923-7534(24)03996-6.

2024年9月15日：S0923-7534（24）03996-6。

De Cock E, Kritikou P, Sandoval M, et al. Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries.

De Cock E，Kritikou P，Sandoval M等。利妥昔单抗皮下注射与利妥昔单抗静脉输注的时间节省：八个国家的时间和运动研究。

PLoS One

公共科学图书馆一号

. 2016;11(6):e0157957.

2016年；11（6）：e0157957。

Lopez-Vivianco G, Salvador J, et al. Cost minimization analysis of treatment with intravenous or subcutaneous trastuzumab in patients with HER2-positive breast cancer in Spain. Clin Transl Oncol. 2017;19(12):1453-1461.

Lopez Vivianco G，Salvador J等。西班牙HER2阳性乳腺癌患者静脉或皮下曲妥珠单抗治疗的成本最小化分析。临床翻译Oncol。2017年；19（12）：1453-1461。

Dent S, Ammndolea C, Christofides A, et al. A multidisciplinary perspective on the subcutaneous administration of trastuzumab in HER2-positive breast cancer. 2019;26(1):e70-e80.

Dent S，Ammndolea C，Christofides A等。关于HER2阳性乳腺癌中曲妥珠单抗皮下给药的多学科观点。2019年；26（1）：e70-e80。

McCloskey C, Ortega MT, Nair S, et al. A Systematic Review of Time and Resource Use Costs of Subcutaneous Versus Intravenous Administration of Oncology Biologics in a Hospital Setting.

McCloskey C，Ortega MT，Nair S等。在医院环境中皮下与静脉注射肿瘤生物制剂的时间和资源使用成本的系统评价。

Pharmacoecon Open

Pharmacoecon公开赛

. 2023;(7)1:3-36.

. 2023;(7)1:3-36.

Bittner B, Schmidt J. Advancing Subcutaneous Dosing Regimens for Biotherapeutics: Clinical Strategies for Expedited Market Access.

Bittner B，Schmidt J.推进生物治疗药物的皮下给药方案：加速市场准入的临床策略。

BioDrugs

生物 药物

. 2024:38(1):23-46.

. 2024:38(1):23-46.

Burcombe R, Chan S, et al. Subcutaneous Trastuzumab (Herceptin®

Burcombe R，Chan S等。皮下曲妥珠单抗（Herceptin®

): A UK Time and Motion Study in Comparison with Intravenous Formulation for the Treatment of Patients with HER2-Positive Early Breast Cancer. Advances in Breast Cancer Research. 2012;2(4).

)：一项英国时间和运动研究，与静脉注射制剂相比，用于治疗HER2阳性早期乳腺癌患者。乳腺癌研究进展。2012年；2（4）。

MedlinePlus.gov. Subcutaneous (SQ) injections. Available at

MedlinePlus.gov。皮下（SQ）注射。可在

https://medlineplus.gov/ency/patientinstructions/000430.htm.

https://medlineplus.gov/ency/patientinstructions/000430.htm.

Accessed November 25, 2024.

2024年11月25日访问。

Leveque D. Subcutaneous administration of anticancer agents.

Leveque D.抗癌剂的皮下给药。

Anticancer Res

抗癌研究

. 2014;34(4):1579-1586.

. 2014;34(4):1579-1586.

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企业金融新闻

Bristol Myers Squibb

百时美施贵宝

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