PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo® (nivolumab), in combination with cisplatin and gemcitabine, for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC), the most common type of bladder cancer.1,2 This approval is based on results from the Phase 3 CheckMate –901 trial which evaluated Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy (n=304), compared to cisplatin-gemcitabine alone (n=304), for patients with previously untreated unresectable or metastatic UC.1,3 The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR).1.

普林斯顿，新泽西州（商业新闻短讯）--百时美施贵宝（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Opdivo®（nivolumab）联合顺铂和吉西他滨用于无法切除或转移性尿路上皮癌（UC）成年患者的一线治疗，最常见的膀胱癌类型。1,2这项批准是基于CheckMate-901期临床试验的结果，该试验评估了Opdivo联合顺铂和吉西他滨，然后是Opdivo单药治疗（n=304），与单独使用顺铂-吉西他滨（n=304）相比，对于先前未经治疗的不可切除或转移性UC患者[1,3]。主要疗效终点是通过盲法独立中央评估（BICR）评估的总生存期（OS）和无进展生存期（PFS）。

In the trial, with a median follow-up of approximately 33 months, treatment with Opdivo in combination with cisplatin and gemcitabine reduced the risk of death by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63, 0.96; p=0.0171).1,4 Patients receiving Opdivo in combination with cisplatin and gemcitabine had their risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012).1.

在该试验中，中位随访时间约为33个月，Opdivo联合顺铂和吉西他滨治疗可将死亡风险降低22%，中位OS为21.7个月，而单用顺铂-吉西他滨为18.9个月（风险比[HR]0.78；95%置信区间[CI]：0.63，0.96；p=0.0171）.1,4接受Opdivo联合顺铂和吉西他滨治疗的患者疾病进展或死亡风险降低了28%，中位PFS为7.9个月，而单用顺铂-吉西他滨为7.6个月（HR 0.72；95%CI:0.59,0.88；p=0.0012）。

Additionally, in exploratory analyses, treatment with Opdivo in combination with cisplatin and gemcitabine resulted in an objective response rate (ORR) of 57.6% (n=175) (95% CI: 51.8, 63.2) versus 43.1% (n=131) (95% CI: 37.5, 48.9) with cisplatin-gemcitabine alone.1,4 The complete response (CR) rate and partial response (PR) rate seen in patients treated with Opdivo in combination with cisplatin and gemcitabine was 22% (n=66) and 36% (n=109), respectively, versus 12% (n=36) and 31% (n=95) with cisplatin-gemcitabine alone.1.

此外，在探索性分析中，Opdivo联合顺铂和吉西他滨治疗的客观缓解率（ORR）为57.6%（n=175）（95%CI:51.8,63.2），而单独使用顺铂-吉西他滨治疗的客观缓解率（ORR）为43.1%（n=131）（95%CI:37.5,48.9）。1,4完全缓解率（CR）和部分缓解率（PR）Opdivo联合顺铂和吉西他滨治疗的患者发生率分别为22%（n=66）和36%（n=109），而单独使用顺铂-吉西他滨的患者发生率分别为12%（n=36）和31%（n=95）。

“This approval marks an important advancement in a historically difficult-to-treat setting, where there has been a need for new and differentiated first-line approaches that may offer patients a chance to live longer,”5 said Guru P. Sonpavde, MD, Medical Director of Genitourinary Oncology and the Phase I Clinical Research Unit and Christopher K.

泌尿生殖系统肿瘤学和I期临床研究部门的医学主任兼Christopher K。

Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, Orlando, Florida. “Based on outcomes and the safety profile seen in the CheckMate -901 clinical trial, the approval of Opdivo in combination with cisplatin and gemcitabine has the potential to change how metastatic or unresectable UC is treated for certain patients and offers them new hope.”1.

佛罗里达州奥兰多市AdventHealth癌症研究所的Glanz膀胱癌研究主席。“根据CheckMate-901临床试验的结果和安全性，Opdivo联合顺铂和吉西他滨的批准有可能改变某些患者转移性或不可切除性UC的治疗方式，并为他们提供新的希望。”。

Opdivo is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

Opdivo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，皮肤病不良反应，肾功能不全的肾炎，其他免疫介导的不良反应；输注相关反应；异基因造血干细胞移植（HSCT）的并发症；胚胎-胎儿毒性；当Opdivo被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，这在对照临床试验之外是不推荐的。

Please see Important Safety Information below.1.

请参阅下面的重要安全信息。

“Bringing Opdivo to the first-line setting in UC with chemotherapy is the latest realization of our history of research and progress in immunotherapy, which has helped transform the treatment landscape for many cancers, including bladder cancer,”1,6 said Wendy Short Bartie, senior vice president and general manager, U.S.

美国高级副总裁兼总经理温迪·肖特·巴蒂（WendyShort Bartie）说：“将Opdivo纳入UC化疗的一线治疗，是我们免疫治疗研究和进展史的最新认识，这有助于改变包括膀胱癌在内的许多癌症的治疗格局。”

Hematology and Oncology at Bristol Myers Squibb. “This milestone adds a meaningful expansion to our portfolio of Opdivo-based treatments in genitourinary cancers, where we now have offerings in UC spanning three indications across stages of disease and treatment needs.”1.

百时美施贵宝的血液学和肿瘤学。“这一里程碑为我们在泌尿生殖系统癌症中基于Opdivo的治疗组合增加了一个有意义的扩展，我们现在在UC中提供了跨越疾病和治疗需求阶段的三个适应症。”

The FDA previously approved Opdivo for the adjuvant treatment of adult patients with UC who are at high risk of recurrence after undergoing radical resection of UC; it also previously approved Opdivo for the treatment of adult patients with locally advanced or metastatic UC who have had disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.1.

FDA先前批准Opdivo用于辅助治疗UC根治术后复发风险高的成年UC患者；它之前还批准Opdivo用于治疗局部晚期或转移性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。

Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) leading to today’s approval was granted Priority Review status by the FDA, and was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.7 The review was also conducted under the FDA’s Project Orbis initiative, which enables concurrent review by the health authorities in several other countries where the application remains under review..

导致今天批准的百时美施贵宝补充生物制剂许可证申请（sBLA）被FDA授予优先审查地位，并在FDA的实时肿瘤学审查（RTOR）试点计划下获得批准，旨在确保尽早为患者提供安全有效的治疗。7该审查也是在FDA的Orbis项目倡议下进行的，该项目使其他几个国家的卫生当局能够同时审查该申请。

About CheckMate -901

关于CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to cisplatin-gemcitabine alone, in patients with previously untreated unresectable or metastatic urothelial cancer.3

CheckMate-901是一项3期随机开放标签试验，评估Opdivo联合顺铂和吉西他滨，然后与单用顺铂-吉西他滨相比，Opdivo单药治疗先前未经治疗的不可切除或转移性尿路上皮癌患者

In the CheckMate -901 study, a total of 608 cisplatin-eligible patients were randomized to receive either Opdivo 360 mg in combination with cisplatin-gemcitabine every three weeks for up to six cycles followed by Opdivo monotherapy 480 mg every 4 weeks until disease progression or unacceptable toxicity up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles.1 The primary endpoints of this study were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR).1,3 The OS and PFS outcomes for cisplatin-eligible patients are based on the final efficacy analyses of these endpoints.4.

在CheckMate-901研究中，共有608名符合顺铂条件的患者被随机分配，每三周接受一次Opdivo 360 mg联合顺铂吉西他滨治疗，最多六个周期，然后每4周接受一次Opdivo 480 mg单药治疗，直到疾病进展或不可接受的毒性最长两年，或每三周单独使用顺铂-吉西他滨，最多六个周期[1]。本研究的主要终点是通过盲法独立中心评价（BICR）评估的总生存期（OS）和无进展生存期（PFS）[1,3]。顺铂合格患者的OS和PFS结果基于这些终点的最终疗效分析。

Select Safety Profile from CheckMate -901

从CheckMate-901中选择安全配置文件

Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).1 The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.1 Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%).1 Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.1.

48%接受Opdivo化疗的患者发生严重不良反应。1接受Opdivo化疗的患者中，≥2%报告的最常见严重不良反应为尿路感染（4.9%），急性肾损伤（4.3%），贫血（3%），肺栓塞（2.6%），败血症（2.3%）和血小板计数下降（2.3%）.1最常见的不良反应（报告≥20%的患者）是恶心，疲劳，肌肉骨骼疼痛，便秘，食欲下降，皮疹，呕吐和周围神经病变。3.6%接受Opdivo化疗的患者发生致命不良反应；其中包括败血症（1%）。30%的患者停止了Opdivo和/或化疗，67%的患者因不良反应而延迟。

About Urothelial Carcinoma

关于尿路上皮癌

Bladder cancer is the sixth most common cancer in the U.S., with an estimated 83,190 new cases expected to be diagnosed in 2024.2,8 Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases.2,8 In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis.2 The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo radical surgery will experience disease progression and recurrence, generally within two years post-surgery.9,10,11,12,13 Approximately 20% to 25% of patients with urothelial carcinoma present with metastatic disease, and treatment challenges have historically persisted in the first- and second-line settings, in part due to limited therapeutic options.13,14,15.

膀胱癌是美国第六大常见癌症，预计2024年将诊断出83190例新病例。尿路上皮癌最常见于膀胱内侧的细胞，约占膀胱癌病例的90%。2,8除膀胱外，尿路上皮癌还可能发生在泌尿道的其他部位，包括输尿管和肾盂。2大多数尿路上皮癌是在早期诊断出来的，但大约50%接受根治性手术的患者通常会在手术后两年内经历疾病进展和复发。9,10,11,12,13大约20%至25%的尿路上皮癌患者患有转移性疾病，治疗挑战在一线和二线环境中一直存在，部分原因是治疗选择有限[13,14,15]。

INDICATION

指示

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

OPDIVO®（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。

IMPORTANT SAFETY INFORMATION

重要安全信息

Severe and Fatal Immune-Mediated Adverse Reactions

严重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. Early identification and management are essential to ensure safe use of OPDIVO.

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后发生。早期识别和管理对于确保OPDIVO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 with OPDIVO. 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OPDIVO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 depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO 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（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，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 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 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，3.1%（61/1994）的患者发生了免疫介导的肺炎，包括4级（<0.1%），3级（0.9%）和2级（2.1%）。

Immune-Mediated Colitis

免疫介导的结肠炎

OPDIVO 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%)..

在接受OPDIVO单药治疗的患者中，2.9%（58/1994）的患者发生了免疫介导的结肠炎，包括3级（1.7%）和2级（1%）。

Immune-Mediated Hepatitis and Hepatotoxicity

免疫介导的肝炎和肝毒性

OPDIVO 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%).

OPDIVO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%）。

Immune-Mediated Endocrinopathies

免疫介导的内分泌病

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

OPDIVO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（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，畏光或视野缺陷。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%).

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%）。

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 monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).

在接受OPDIVO单药治疗的患者中，甲状腺炎发生率为0.6%（12/1994），包括2级（0.2%）。

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%).

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%）。

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%).

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%）。

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.

在接受OPDIVO单药治疗的患者中，糖尿病发生率为0.9%（17/1994），包括3级（0.4%）和2级（0.3%），以及2例糖尿病酮症酸中毒。

Immune-Mediated Nephritis with Renal Dysfunction

免疫介导性肾炎伴肾功能不全

OPDIVO 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%).

OPDIVO可引起免疫介导的肾炎。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%）。

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。

Withhold or permanently discontinue OPDIVO 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（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%).

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%）。

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 were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): 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..

在接受OPDIVO单药治疗或报告使用其他PD-1/PD-L1阻断抗体的患者中，以下临床上显着的免疫介导的不良反应发生率<1%（除非另有说明）。据报道，其中一些不良反应有严重或致命的病例：心脏/血管：心肌炎，心包炎，血管炎；神经系统：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；眼部：可能发生葡萄膜炎，虹膜炎和其他眼部炎症毒性；胃肠道：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；肌肉骨骼和结缔组织：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；内分泌：甲状旁腺功能减退；其他（血液学/免疫）：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（Kikuchi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, which has been observed in patients receiving OPDIVO, 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的患者中观察到的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。

Infusion-Related Reactions

输液相关反应

OPDIVO can cause severe infusion-related reactions. Discontinue OPDIVO 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. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients.

OPDIVO可引起严重的输液相关反应。严重（3级）或危及生命（4级）输注相关反应的患者停止使用OPDIVO。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。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。

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. 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..

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。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。

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. 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 and allogeneic HSCT..

尽管OPDIVO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 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之前或之后使用OPDIVO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 can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose..

根据其作用机制和动物研究结果，OPDIVO给孕妇服用时可能会造成胎儿伤害。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治疗期间以及最后一次服用后至少5个月内使用有效的避孕措施。

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 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OPDIVO的存在，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5个月内不要母乳喂养。

Serious Adverse Reactions

严重不良反应

In Checkmate 901, serious adverse reactions occurred in 48% of patients receiving OPDIVO in combination with chemotherapy. The most frequent serious adverse reactions reporting in ≥2% of patients who received OPDIVO with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).

在Checkmate 901中，48%接受OPDIVO联合化疗的患者发生严重不良反应。在接受OPDIVO化疗的患者中，≥2%的患者报告最常见的严重不良反应是尿路感染（4.9%），急性肾损伤（4.3%），贫血（3%），肺栓塞（2.6%），败血症（2.3%），血小板计数下降（2.3%）。

Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction..

接受OPDIVO联合化疗的患者中有3.6%发生致命的不良反应；其中包括败血症（1%）。30%的患者停止了OPDIVO和/或化疗，67%的患者因不良反应而延迟。

Common Adverse Reactions

常见不良反应

In Checkmate 901, the most common adverse reactions (≥20%) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.

在Checkmate 901中，最常见的不良反应（≥20%）是恶心，疲劳，肌肉骨骼疼痛，便秘，食欲下降，皮疹，呕吐和周围神经病变。

Please see US Full Prescribing Information for OPDIVO.

请参阅OPDIVO的完整处方信息。

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.

BMS Access Support®（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 at 1-800-861-0048 or by visiting www.bmsaccesssupport.com..

有关我们的访问和报销支持的更多信息，请拨打BMS访问支持电话1-800-861-0048或访问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 Opdivo 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..

2011年，百时美施贵宝通过与小野制药公司的合作协议，扩大了其在全球范围内开发和商业化Opdivo的领土权利，但日本、韩国和台湾除外，小野当时保留了该化合物的所有权利。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 BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram..

百时美施贵宝是一家全球生物制药公司，其使命是发现、开发和提供创新药物，帮助患者战胜严重疾病。有关百时美施贵宝的更多信息，请访问BMS.com或在LinkedIn、Twitter、YouTube、Facebook和Instagram上关注我们。

U.S. Food & Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-cener-excellence/real-time-oncology-review. Accessed February 06, 2024.

U美国食品和药物管理局实时肿瘤学审查试点计划。https://www.fda.gov/about-fda/oncology-cener-excellence/real-time-oncology-review.2024年2月6日访问。

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Dason S，Cha EK，Falavolti C等。根治性膀胱切除术后晚期复发有不同的预后和管理考虑。J乌拉尔。2020年；204（3）：460-465。doi:10.1097/JU.0000000000001028