- Priority review designation is based on results from the Phase 3 EV-302 trial, which found enfortumab vedotin plus pembrolizumab significantly extended overall survival and progression free survival compared to platinum-containing chemotherapy-

-优先审查指定是基于第3阶段EV-302试验的结果，该试验发现，与含铂化疗相比，enfortumab vedotin加pembrolizumab可显着延长总生存期和无进展生存期-

TOKYO, Feb. 15, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, 'Astellas') today announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has granted priority review for the company's Supplemental New Drug Application (sNDA) for PADCEV™ (enfortumab vedotin (genetical recombination)) with KEYTRUDA® (pembrolizumab (genetical recombination)) as a combination therapy for the first-line treatment of adult patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC).

东京，2024年2月15日/PRNewswire/--Astellas Pharma Inc.（东京证交所：4503，总裁兼首席执行官：冈村直树（Naoki Okamura），“Astellas”）今天宣布，日本厚生劳动省（MHLW）已批准优先审查该公司针对PADCEV™（enfortumab vedotin（genetical recombination））和KEYTRUDA®（pembrolizumab（genetical recombination））的补充新药申请（sNDA）)作为先前未经治疗的局部晚期或转移性尿路上皮癌（la/mUC）成年患者的一线治疗的联合疗法。

The sNDA was submitted in January 2024. If approved, PADCEV with KEYTRUDA has the potential to change the treatment paradigm, becoming the first combination treatment to offer an alternative to platinum-containing chemotherapy, the current standard of care in first-line la/mUC. .

sNDA于2024年1月提交。如果获得批准，PADCEV与KEYTRUDA有可能改变治疗模式，成为第一个联合治疗方案，为一线la/mUC的当前标准治疗方案含铂化疗提供替代方案。。

Priority reviews are granted by MHLW for applications based on their clinical usefulness and the seriousness of the diseases for which they are indicated.i The sNDA for the first-line use of this combination is based on results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39). The study found the combination improved overall survival (OS) and progression-free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated la/mUC compared to platinum-containing chemotherapy.

MHLW根据其临床实用性和所指示疾病的严重程度对申请进行优先审查。这种组合的一线使用的sNDA基于第3阶段EV-302临床试验的结果（也称为KEYNOTE-A39）。该研究发现，与含铂化疗相比，该组合改善了先前未经治疗的la/mUC患者的总生存期（OS）和无进展生存期（PFS），具有统计学意义和临床意义。

The safety results were consistent with those previously reported with this combination, and no new safety issues were identified. .

安全性结果与之前报道的这种组合一致，没有发现新的安全问题。。

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas 'The MHLW's priority review for our application for PADCEV in combination with pembrolizumab reflects the significance of the EV-302 trial findings and the urgent need for innovative new treatment options. We are pleased by this review designation and hope to quickly bring this treatment option to those who need it most.'.

AhsanArozullah，医学博士，医学博士，高级副总裁，肿瘤学发展负责人，Astellas的MHLW对我们应用PADCEV联合pembrolizumab的优先审查反映了EV-302试验结果的重要性以及对创新新治疗方案的迫切需要。我们对这一审查指定感到高兴，并希望尽快将这种治疗选择带给最需要的人。”。

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is also reviewing the combination therapy. The U.S. Food and Drug Administration approved the combination therapy in December 2023.

欧洲药品管理局（European Medicines Agency）的人用药品委员会（CHMP）也正在审查联合疗法。美国食品和药物管理局于2023年12月批准了这种联合疗法。

Globally, approximately 614,000 new cases of bladder cancer and approximately 220,000 deaths are reported annually.ii It is estimated that approximately 25,000 people in Japan are diagnosed with bladder cancer each year and approximately 10,000 deaths were reported in 2022.iii

在全球范围内，每年报告约614000例新发膀胱癌病例，约220000例死亡。据估计，日本每年约有25000人被诊断出患有膀胱癌，2022年约有10000人死亡

About EV-302The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status.

关于EV-302 EV-302试验是一项开放标签，随机，对照的3期研究，评估enfortumab vedotin联合pembrolizumab与先前未治疗的la/mUC患者的含铂化疗。该研究招募了886名先前未经治疗的la/mUC患者，无论PD-L1状态如何，他们都有资格接受含顺铂或卡铂的化疗。

Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety..

患者被随机分配接受enfortumab vedotin联合pembrolizumab或含铂化疗。该试验的双重主要终点是通过盲法独立中央审查（BICR）每个RECIST v1.1的OS和PFS。选择次要终点包括BICR的每个RECIST v1.1的ORR，BICR的每个RECIST v1.1的DOR和安全性。。

The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the European Society for Medical Oncology (ESMO) Congress 2023 in October 2023.

EV-302试验是一项广泛的临床计划的一部分，该计划评估了尿路上皮癌和其他实体瘤的多个阶段的这种组合。EV-302的研究结果于2023年10月在2023年欧洲肿瘤内科学会（ESMO）大会上发表。

About Bladder and Urothelial Cancer

关于膀胱癌和尿路上皮癌

Urothelial cancer, or bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs.iv

尿路上皮癌或膀胱癌始于尿道、膀胱、输尿管、肾盂和其他一些器官的尿路上皮细胞

If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease. If the cancer has spread to other parts of the body, it is called metastatic disease.v

如果膀胱癌扩散到周围器官或肌肉，则称为局部晚期疾病。如果癌症已经扩散到身体的其他部位，则称为转移性疾病。五

Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter, and urethra.iii

尿路上皮癌占所有膀胱癌的90%，也可以在肾盂，输尿管和尿道中发现

Approximately 12% of cases are locally advanced or metastatic urothelial cancer at diagnosis.vi

大约12%的病例在诊断时是局部晚期或转移性尿路上皮癌

Ongoing Investigational Trials The EV-302 trial (NCT04223856) is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. .

正在进行的研究性试验EV-302试验（NCT04223856）是一项开放标签，随机，对照的3期研究，评估enfortumab vedotin联合pembrolizumab与含铂化疗对先前未经治疗的局部晚期或转移性尿路上皮癌（la/mUC）患者的疗效无论PD-L1状态如何，都有资格接受含顺铂或卡铂的化疗。。

The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 study investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and patients with muscle-invasive bladder cancer (MIBC)..

EV-103试验（NCT03288545）是一项正在进行的多队列，开放标签，多中心1b/2期研究，研究了单用或联合pembrolizumab和/或化疗在la/mUC患者和肌肉浸润性膀胱癌（MIBC）患者的一线或二线治疗中的应用。。

Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective..

Enfortumab vedotin联合pembrolizumab正在尿路上皮癌多个阶段的广泛项目中进行研究，包括EV-304（NCT04700124，也称为KEYNOTE-B15）和EV-303（NCT03924895，也称为KEYNOTE-905）中MIBC的两项3期临床试验。enfortumab vedotin联合pembrolizumab治疗二线尿路上皮癌和MIBC尚未被证明是安全或有效的。。

The EV-202 trial (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 study investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This study also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent/ metastatic head and neck squamous cell carcinoma..

EV-202试验（NCT04225117）是一项正在进行的多队列，开放标签，多中心的2期研究，研究了先前治疗过的晚期实体瘤患者单独使用enfortumab vedotin。这项研究还有一个队列，正在研究enfortumab vedotin联合pembrolizumab治疗先前未经治疗的复发/转移性头颈部鳞状细胞癌患者。。

About PADCEV™ (enfortumab vedotin (genetical recombination)) PADCEV (enfortumab vedotin (genetical recombination)) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.vi Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which results in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).vii .

关于PADCEV™（enfortumab vedotin（基因重组））PADCEV（enfortumab vedotin（基因重组））是针对Nectin-4的一流抗体-药物偶联物（ADC），Nectin-4是一种位于细胞表面并在膀胱癌中高度表达的蛋白质。vi非临床数据表明，PADCEV的抗癌活性是由于其与表达Nectin-4的细胞结合，然后将抗肿瘤剂单甲基auristatin E（MMAE）内化并释放到细胞中，导致细胞不繁殖（细胞周期停滞）和程序性细胞死亡（细胞凋亡）。

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

PADCEV（enfortumab vedotin ejfv）美国指示和重要安全信息

BOXED WARNING: SERIOUS SKIN REACTIONS

盒装警告：严重的皮肤反应

PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occur predominantly during the first cycle of treatment but may occur later.

PADCEV可引起严重和致命的皮肤不良反应，包括史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN），主要发生在第一个治疗周期，但可能会在以后发生。

Closely monitor patients for skin reactions.

密切监测患者的皮肤反应。

Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.

立即停止PADCEV，并考虑转诊接受疑似SJS或TEN或严重皮肤反应的专业护理。

Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

确诊为SJS或TEN的患者永久停用PADCEV；或4级或复发性3级皮肤反应。

Indication

指示

PADCEV®, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).

PADCEV®与pembrolizumab联合用于治疗局部晚期或转移性尿路上皮癌（mUC）的成年患者。

PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or mUC who:

PADCEV作为单一药物，适用于治疗局部晚期或mUC的成年患者，这些患者：

have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or

先前曾接受过程序性死亡受体1（PD-1）或程序性死亡配体1（PD-L1）抑制剂和含铂化疗，或

are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

不符合含顺铂化疗的资格，并且之前曾接受过一种或多种治疗方案。

IMPORTANT SAFETY INFORMATION

重要安全信息

Warnings and Precautions

警告和注意事项

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 70% (all grades) of the 564 patients treated with PADCEV in combination with pembrolizumab in clinical trials.

皮肤反应 PADCEV治疗的患者发生严重的皮肤不良反应，包括致命的SJS或TEN病例。SJS和TEN主要发生在第一个治疗周期，但可能会在以后发生。在临床试验中，PADCEV联合pembrolizumab治疗的564例患者中有70%（所有级别）发生皮肤反应。

When PADCEV was given in combination with pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate compared to PADCEV as a single agent. The majority of the skin reactions that occurred with combination therapy included maculo-papular rash, macular rash and papular rash.

当PADCEV与pembrolizumab联合使用时，与PADCEV作为单一药物相比，皮肤反应（包括严重事件）的发生率更高。联合治疗发生的大多数皮肤反应包括斑丘疹，黄斑疹和丘疹。

Grade 3-4 skin reactions occurred in 17% of patients (Grade 3: 16%, Grade 4: 1%), including maculo-papular rash, bullous dermatitis, dermatitis, exfoliative dermatitis, pemphigoid, rash, erythematous rash, macular rash, and papular rash. A fatal reaction of bullous dermatitis occurred in one patient (0.2%).

17%的患者发生3-4级皮肤反应（3级：16%，4级：1%），包括斑丘疹，大疱性皮炎，皮炎，剥脱性皮炎，类天疱疮，皮疹，红斑疹，黄斑疹和丘疹。一名患者（0.2%）发生大疱性皮炎的致命反应。

The median time to onset of severe skin reactions was 1.7 months (range: 0.1 to 17.2 months). Skin reactions led to discontinuation of PADCEV in 6% of patients. .

严重皮肤反应发作的中位时间为1.7个月（范围：0.1至17.2个月）。皮肤反应导致6%的患者停用PADCEV。。

Skin reactions occurred in 58% (all grades) of the 720 patients treated with PADCEV as a single agent in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 34% had pruritus. Grade 3-4 skin reactions occurred in 14% of patients, including maculo-papular rash, erythematous rash, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia.

在临床试验中，使用PADCEV作为单一药物治疗的720例患者中，有58%（所有级别）发生皮肤反应。23%的患者有斑丘疹，34%的患者有瘙痒。14%的患者发生3-4级皮肤反应，包括斑丘疹，红斑疹，皮疹或药疹，对称性药物相关性三叉间和弯曲性皮疹（SDRIFE），大疱性皮炎，剥脱性皮炎和掌底红细胞感觉异常。

The median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 8 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=75), 24% of patients restarting at the same dose and 24% of patients restarting at a reduced dose experienced recurrent severe skin reactions.

严重皮肤反应发作的中位时间为0.6个月（范围：0.1至8个月）。在经历导致剂量中断的皮肤反应的患者中，然后重新开始PADCEV（n=75），24%的患者以相同剂量重新开始，24%的患者以减少剂量重新开始，经历了反复的严重皮肤反应。

Skin reactions led to discontinuation of PADCEV in 3.1% of patients. .

皮肤反应导致3.1%的患者停用PADCEV。。

Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. For persistent or recurrent Grade 2 skin reactions, consider withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for Grade 3 skin reactions.

在整个治疗过程中密切监测患者的皮肤反应。根据临床指示，考虑局部使用皮质类固醇和抗组胺药。对于持续性或复发性2级皮肤反应，考虑扣留PADCEV直至≤1级。保留PADCEV，并针对疑似SJS，TEN或3级皮肤反应进行专门护理。

Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions. .

确诊为SJS或TEN的患者永久停用PADCEV；或4级或复发性3级皮肤反应。。

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials of PADCEV as a single agent, 17% of the 720 patients treated with PADCEV developed hyperglycemia of any grade; 7% of patients developed Grade 3-4 hyperglycemia (Grade 3: 6.5%, Grade 4: 0.6%).

高血糖 和糖尿病酮症酸中毒（DKA），包括致命事件，发生在患有和不患有PADCEV的糖尿病患者中。基线血红蛋白A1C≥8%的患者被排除在临床试验之外。在PADCEV作为单一药物的临床试验中，接受PADCEV治疗的720名患者中有17%出现了任何级别的高血糖症；7%的患者出现3-4级高血糖（3级：6.5%，4级：0.6%）。

Fatal events of hyperglycemia and DKA occurred in one patient each (0.1%). The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. The median time to onset of hyperglycemia was 0.5 months (range: 0 to 20 months).

高血糖和DKA致命事件各发生一例（0.1%）。体重指数较高的患者和基线A1C较高的患者3-4级高血糖的发生率持续增加。高血糖发作的中位时间为0.5个月（范围：0至20个月）。

Hyperglycemia led to discontinuation of PADCEV in 0.7% of patients. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. Of the patients who initiated insulin therapy for treatment of hyperglycemia, 66% (23/35) discontinued insulin at the time of last evaluation.

高血糖导致0.7%的患者停用PADCEV。5%（5%）的患者需要开始胰岛素治疗以治疗高血糖症。在开始胰岛素治疗以治疗高血糖的患者中，66%（23/35）在上次评估时停止了胰岛素治疗。

Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV. .

密切监测患有或有糖尿病或高血糖风险的患者的血糖水平。如果血糖升高（>250 mg/dL），则停止使用PADCEV。。

Pneumonitis/Interstitial Lung Disease (ILD) Severe, life-threatening or fatal pneumonitis/ILD occurred in patients treated with PADCEV. When PADCEV was given in combination with pembrolizumab, 10% of the 564 patients treated with combination therapy had pneumonitis/ILD of any grade and 4% had Grade 3-4.

肺炎/间质性肺病（ILD） PADCEV治疗的患者发生严重，危及生命或致命的肺炎/ILD。当PADCEV与pembrolizumab联合使用时，联合治疗的564例患者中有10%患有任何级别的肺炎/ILD，4%患有3-4级。

A fatal event of pneumonitis/ILD occurred in two patients (0.4%). The incidence of pneumonitis/ILD, including severe events, occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent. The median time to onset of any grade pneumonitis/ILD was 4 months (range: 0.3 to 26 months). .

两名患者（0.4%）发生肺炎/ILD致命事件。与PADCEV作为单一药物相比，当PADCEV与pembrolizumab联合使用时，肺炎/ILD（包括严重事件）的发生率更高。任何级别肺炎/ILD发病的中位时间为4个月（范围：0.3至26个月）。。

In clinical trials of PADCEV as a single agent, 3% of the 720 patients treated with PADCEV had pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median time to onset of any grade pneumonitis/ILD was 2.9 months (range: 0.6 to 6 months).

在PADCEV作为单一药物的临床试验中，接受PADCEV治疗的720例患者中有3%患有任何级别的肺炎/ILD，0.8%患有3-4级。任何级别肺炎/ILD发病的中位时间为2.9个月（范围：0.6至6个月）。

Monitor patients for signs and symptoms indicative of pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop Grade 2 pneumonitis/ILD and consider dose reduction.

在放射学检查中监测患者是否有肺炎/ILD的体征和症状，例如缺氧，咳嗽，呼吸困难或间质浸润。通过适当的调查，评估并排除此类体征和症状的传染性，肿瘤性和其他原因。对于发生2级肺炎/ILD并考虑减少剂量的患者，保留PADCEV。

Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis/ILD. .

所有3级或4级肺炎/ILD患者永久停用PADCEV。。

Peripheral neuropathy (PN) When PADCEV was given in combination with pembrolizumab, 67% of the 564 patients treated with combination therapy had PN of any grade, 36% had Grade 2 neuropathy, and 7% had Grade 3 neuropathy. The incidence of PN occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent.

周围神经病（PN） 当PADCEV与pembrolizumab联合使用时，联合治疗的564例患者中有67%患有任何级别的PN，36%患有2级神经病，7%患有3级神经病。与PADCEV作为单一药物相比，当PADCEV与pembrolizumab联合使用时，PN的发生率更高。

The median time to onset of Grade ≥2 PN was 6 months (range: 0.3 to 25 months). PN occurred in 53% of the 720 patients treated with PADCEV as a single agent in clinical trials including 38% with sensory neuropathy, 8% with muscular weakness and 7% with motor neuropathy. Thirty percent of patients experienced Grade 2 reactions and 5% experienced Grade 3-4 reactions.

≥2级PN发病的中位时间为6个月（范围：0.3至25个月）。在临床试验中，使用PADCEV作为单一药物治疗的720例患者中，有53%发生PN，其中38%患有感觉神经病，8%患有肌肉无力，7%患有运动神经病。30%的患者经历了2级反应，5%的患者经历了3-4级反应。

PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.9 months (range: 0.1 to 20 months). Neuropathy led to treatment discontinuation in 6% of patients. .

PADCEV治疗的患者有或没有既往PN发生PN。≥2级PN发病的中位时间为4.9个月（范围：0.1至20个月）。神经病导致6%的患者停止治疗。。

Monitor patients for symptoms of new or worsening PN and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

监测患者是否出现新的或恶化的PN症状，并在PN发生时考虑剂量中断或PADCEV剂量减少。对于PN≥3级的患者，永久停用PADCEV。

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV as a single agent in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy.

眼部疾病 在计划进行眼科检查的临床试验中，384名接受PADCEV治疗的患者中有40%报告了这种情况。这些事件中的大多数涉及角膜，包括与干眼症相关的事件，例如角膜炎，视力模糊，流泪增加，结膜炎，角膜缘干细胞缺乏症和角膜病变。

Dry eye symptoms occurred in 30% of patients, and blurred vision occurred in 10% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.7 months (range: 0 to 30.6 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve.

在使用PADCEV治疗期间，30%的患者出现干眼症，10%的患者出现视力模糊。症状性眼部疾病的中位发病时间为1.7个月（范围：0至30.6个月）。监测患者的眼部疾病。如果眼部症状出现或无法缓解，请考虑人工泪液预防干眼症和眼科评估。

Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders. .

如果眼科检查后有指示，请考虑使用眼用局部类固醇治疗。对于症状性眼部疾病，请考虑中断剂量或减少剂量的PADCEV。。

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 720 patients treated with PADCEV as a single agent in clinical trials, 1% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions.

输液部位外渗 在施用PADCEV后观察到继发于外渗的皮肤和软组织反应。在临床试验中使用PADCEV作为单一药物治疗的720例患者中，1%的患者出现皮肤和软组织反应，其中0.3%的患者出现3-4级反应。

Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration.

反应可能会延迟。外渗后2-7天，红斑，肿胀，体温升高和疼痛恶化，并在高峰后1-4周内消退。两名患者（0.3%）出现继发性蜂窝织炎，大疱或脱落的外渗反应。在开始PADCEV之前确保足够的静脉通路，并在给药期间监测可能的外渗。

If extravasation occurs, stop the infusion and monitor for adverse reactions. .

如果发生外渗，停止输注并监测不良反应。。

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose. .

胚胎-胎儿毒性 PADCEV给孕妇服用时会对胎儿造成伤害。告知患者对胎儿的潜在风险。建议有生殖潜力的女性患者在PADCEV治疗期间和最后一剂后2个月内使用有效的避孕方法。建议有生殖潜力的女性伴侣的男性患者在使用PADCEV治疗期间和最后一次服用后4个月内使用有效的避孕方法。。

ADVERSE REACTIONS

不良反应

Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV in combination with pembrolizumab) Increased aspartate aminotransferase (AST), increased creatinine, rash, increased glucose, PN, increased lipase, decreased lymphocytes, increased alanine aminotransferase (ALT), decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection and decreased platelets. .

最常见的不良反应，包括实验室异常 （≥20%）（PADCEV联合pembrolizumab） 天冬氨酸氨基转移酶（AST）升高，肌酐升高，皮疹，葡萄糖升高，PN升高，脂肪酶升高，淋巴细胞减少，丙氨酸氨基转移酶（ALT）升高，血红蛋白降低，疲劳，钠降低，磷酸盐降低，白蛋白降低，瘙痒，腹泻，脱发，体重减轻，食欲下降，尿酸盐升高，中性粒细胞减少，钾减少，干眼症，恶心，便秘，钾增加，味觉障碍，尿路感染和血小板减少。。

Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV monotherapy) Increased glucose, increased AST, decreased lymphocytes, increased creatinine, rash, fatigue, PN, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased ALT, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, dry skin. .

最常见的不良反应，包括实验室异常（≥20%）（PADCEV单药治疗） 血糖升高，AST升高，淋巴细胞减少，肌酐升高，皮疹，疲劳，PN，白蛋白降低，血红蛋白降低，脱发，食欲下降，中性粒细胞减少，钠降低，ALT升高，磷酸盐降低，腹泻，恶心，瘙痒，尿酸盐升高，干眼症，味觉障碍，便秘，脂肪酶升高，体重下降，血小板减少，腹痛，皮肤干燥。。

EV-302 Study: 440 patients with previously untreated la/mUC (PADCEV in combination with pembrolizumab)

EV-302研究：440名先前未经治疗的la/mUC患者（PADCEV联合pembrolizumab）

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab. The most common serious adverse reactions (≥2%) were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Fatal adverse reactions occurred in 3.9% of patients treated with PADCEV in combination with pembrolizumab including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).

严重不良反应 PADCEV联合pembrolizumab治疗的患者中有50%发生了这种情况。最常见的严重不良反应（≥2%）是皮疹（6%），急性肾损伤（5%），肺炎/ILD（4.5%），尿路感染（3.6%），腹泻（3.2%），肺炎（2.3%），发热（2%）和高血糖（2%）。 致命不良反应 PADCEV联合pembrolizumab治疗的患者中有3.9%发生急性呼吸衰竭（0.7%），肺炎（0.5%）和肺炎/ILD（0.2%）。

Adverse reactions leading to discontinuation of PADCEV occurred in 35% of patients. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were PN (15%), rash (4.1%) and pneumonitis/ILD (2.3%). Adverse reactions leading to dose interruption of PADCEV occurred in 73% of patients.

35%的患者发生了导致停用PADCEV的不良反应。The 最常见的不良反应（≥2%）导致停药 PADCEV的发生率为PN（15%），皮疹（4.1%）和肺炎/ILD（2.3%）。73%的患者发生了导致PADCEV剂量中断的不良反应。

The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were PN (22%), rash (16%), COVID-19 (10%), diarrhea (5%), pneumonitis/ILD (4.8%), fatigue (3.9%), hyperglycemia (3.6%), increased ALT (3%) and pruritus (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 42% of patients.

The 最常见的不良反应（≥2%）导致剂量中断 PADCEV的发生率为PN（22%），皮疹（16%），新型冠状病毒肺炎（10%），腹泻（5%），肺炎/ILD（4.8%），疲劳（3.9%），高血糖（3.6%），ALT升高（3%）和瘙痒（2.5%）。42%的患者发生了导致PADCEV剂量减少的不良反应。

The most common adverse reactions (≥2%) leading to dose reduction of PADCEV were rash (16%), PN (13%) and fatigue (2.7%). .

The 最常见的不良反应（≥2%）导致剂量减少 PADCEV的发生率为皮疹（16%），PN（13%）和疲劳（2.7%）。。

EV-103 Study: 121 patients with previously untreated la/mUC who were not eligible for cisplatin-containing chemotherapy (PADCEV in combination with pembrolizumab)

EV-103研究：121名先前未经治疗的la/mUC患者不符合含顺铂化疗的条件（PADCEV联合pembrolizumab）

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab; the most common (≥2%) were acute kidney injury (7%), urinary tract infection (7%), urosepsis (5%), sepsis (3.3%), pneumonia (3.3%), hematuria (3.3%), pneumonitis/ILD (3.3%), urinary retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%), myositis (2.5%), anemia (2.5%), and hypotension (2.5%). Fatal adverse reactions occurred in 5% of patients treated with PADCEV in combination with pembrolizumab, including sepsis (1.6%), bullous dermatitis (0.8%), myasthenia gravis (0.8%), and pneumonitis/ILD (0.8%). Adverse reactions leading to discontinuation of PADCEV occurred in 36% of patients; the most common (≥2%) were PN (20%) and rash (6%). Adverse reactions leading to dose interruption of PADCEV occurred in 69% of patients; the most common (≥2%) were PN (18%), rash (12%), increased lipase (6%), pneumonitis/ILD (6%), diarrhea (4.1%), acute kidney injury (3.3%), increased ALT (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract infection (3.3%), increased amylase (2.5%), anemia (2.5%), COVID-19 (2.5%), hyperglycemia (2.5%), and hypotension (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 45% of patients; the most common (≥2%) were PN (17%), rash (12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%). .

严重不良反应 发生在50%的PADCEV联合pembrolizumab治疗的患者中；最常见的（≥2%）是急性肾损伤（7%），尿路感染（7%），尿脓毒症（5%），败血症（3.3%），肺炎（3.3%），血尿（3.3%），肺炎/ILD（3.3%），尿潴留（2.5%），腹泻（2.5%），重症肌无力（2.5%），肌炎（2.5%），贫血（2.5%）和低血压（2.5%）。 致命不良反应 PADCEV联合pembrolizumab治疗的患者中有5%发生，包括败血症（1.6%），大疱性皮炎（0.8%），重症肌无力（0.8%）和肺炎/ILD（0.8%）。 导致停药的不良反应 PADCEV的发生率为36%；最常见（≥2%）是PN（20%）和皮疹（6%）。 导致剂量中断的不良反应 PADCEV的发生率为69%；最常见的（≥2%）是PN（18%），皮疹（12%），脂肪酶升高（6%），肺炎/ILD（6%），腹泻（4.1%），急性肾损伤（3.3%），ALT升高（3.3%），疲劳（3.3%），中性粒细胞减少（3.3%），尿路感染（3.3%），淀粉酶升高（2.5%），贫血（2.5%），COVID-19（2.5%），高血糖（2.5%）和低血压（2.5%）。 导致剂量减少的不良反应 PADCEV的发生率为45%；最常见的（≥2%）是PN（17%），皮疹（12%），疲劳（5%），中性粒细胞减少（5%）和腹泻（4.1%）。。

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy (PADCEV monotherapy)

EV-301研究：296名先前接受PD-1/L1抑制剂和铂类化疗的患者 （PADCEV单一疗法）

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each), and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis/ILD, and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%), and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite, and fatigue (3% each). .

严重不良反应 发生在47%接受PADCEV治疗的患者中；最常见的（≥2%）是尿路感染，急性肾损伤（各7%）和肺炎（5%）。 致命不良反应 发生在3%的患者中，包括多器官功能障碍（1%），肝功能障碍，感染性休克，高血糖，肺炎/ILD和盆腔脓肿（各0.3%）。 导致停药的不良反应 发生在17%的患者中；最常见（≥2%）是PN（5%）和皮疹（4%）。 导致剂量中断的不良反应 发生在61%的患者中；最常见的（≥4%）是PN（23%），皮疹（11%）和疲劳（9%）。 导致剂量减少的不良反应 发生在34%的患者中；最常见的（≥2%）是PN（10%），皮疹（8%），食欲下降和疲劳（各3%）。。

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for cisplatin-based chemotherapy (PADCEV monotherapy)

EV-201，队列2研究：89名先前接受PD-1/L1抑制剂治疗但不符合顺铂化疗（PADCEV单药治疗）条件的患者

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis, and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia, and pneumonitis/ILD (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), increased AST, and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%), and fatigue (7%). .

严重不良反应 发生在39%接受PADCEV治疗的患者中；最常见（≥3%）是肺炎，败血症和腹泻（各5%）。 致命不良反应 发生在8%的患者中，包括急性肾损伤（2.2%），代谢性酸中毒，败血症，多器官功能障碍，肺炎和肺炎/ILD（各1.1%）。 导致停药的不良反应 发生在20%的患者中；最常见（≥2%）是PN（7%）。 导致剂量中断的不良反应 发生在60%的患者中；最常见的（≥3%）是PN（19%），皮疹（9%），疲劳（8%），腹泻（5%），AST升高和高血糖（各3%）。 导致剂量减少的不良反应 发生在49%的患者中；最常见的（≥3%）是PN（19%），皮疹（11%）和疲劳（7%）。。

DRUG INTERACTIONS

药物相互作用

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors) Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors. .

其他药物对PADCEV的影响 （双重P-gp和强CYP3A4抑制剂）与双重P-gp和强CYP3A4抑制剂同时使用可能会增加未结合的单甲基auristatin E暴露，这可能会增加PADCEV毒性的发生率或严重程度。当PADCEV与双重P-gp和强CYP3A4抑制剂同时服用时，密切监测患者的毒性迹象。。

SPECIFIC POPULATIONS

特定人群

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for 3 weeks after the last dose.

哺乳期 建议哺乳期妇女在使用PADCEV治疗期间和最后一次给药后3周内不要母乳喂养。

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

肝损害 避免在中度或重度肝功能损害患者中使用PADCEV。

For more information, please see the U.S. full Prescribing Information including BOXED WARNING for PADCEV here.

有关更多信息，请参阅美国完整的处方信息，包括PADCEV的盒装警告 在这里。

About AstellasAstellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality.

关于AstellasAstellas Pharma Inc.是一家在全球70多个国家开展业务的制药公司。我们正在推动重点领域方法，该方法旨在通过关注生物学和模式，确定持续开发新药的机会，以解决医疗需求未得到满足的疾病。

Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients.

此外，我们还着眼于超越Rx的基础重点，创建Rx+®医疗保健解决方案，将我们的专业知识与外部合作伙伴不同领域的尖端技术相结合。通过这些努力，Astellas站在医疗保健变革的前沿，将创新科学转化为患者的价值。

For more information, please visit our website at https://www.astellas.com/en..

欲了解更多信息，请访问我们的网站https://www.astellas.com/en..

About the Astellas, Pfizer and Merck CollaborationAstellas and Pfizer have a clinical collaboration agreement with Merck to evaluate the combination of Astellas' and Pfizer's PADCEV™ (enfortumab vedotin) and Merck's KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer.

关于Astellas，辉瑞和默克公司的合作Astellas和辉瑞公司与默克公司签订了临床合作协议，以评估Astellas和辉瑞公司的PADCEV™（enfortumab vedotin）和默克公司的KEYTRUDA®（pembrolizumab）在先前未经治疗的转移性尿路上皮癌患者中的组合。

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada)..

KEYTRUDA是默克公司（Merck&Co.，Inc.，Rahway，NJ，USA）（在美国和加拿大以外称为MSD）的子公司默克夏普公司（Merck Sharp&Dohme Corp.）的注册商标。。

Astellas Cautionary NotesIn this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties.

Astellas警示语在本新闻稿中，有关当前计划、估计、战略和信念的声明以及其他非历史事实的声明是关于Astellas未来表现的前瞻性声明。这些声明基于管理层目前的假设和信念，并根据目前可获得的信息，涉及已知和未知的风险和不确定性。

A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties..

许多因素可能导致实际结果与前瞻性声明中讨论的结果存在重大差异。这些因素包括但不限于：（i）与药品市场有关的一般经济条件和法律法规的变化，（ii）货币汇率波动，（iii）新产品发布的延迟，（iv）阿斯特拉斯无法有效地营销现有产品和新产品，（v）Astellas无法在竞争激烈的市场上继续有效地研究和开发客户接受的产品，以及（vi）第三方侵犯了Astellas的知识产权。。

Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

本新闻稿中包含的有关药品（包括目前正在开发的产品）的信息无意构成广告或医疗建议。

i Pharmaceuticals and Medical Devices Agency. Drug Reviews. https://www.pmda.go.jp/english/review-services/reviews/0001.html. Accessed February 1, 2024ii International Agency for Research on Cancer. Cancer Today: bladder globocan 2022 fact sheet (01-2024). 30-bladder-fact-sheet.pdf (who.int)iii Cancer Information Service, Cancer Statistics in Japan.

i药品和医疗器械管理局。药物评论。（笑声）https://www.pmda.go.jp/english/review-services/reviews/0001.html.2024ii年2月1日访问国际癌症研究机构。《今日癌症》：膀胱globocan 2022简介（01-2024）。30-bladder-fact-sheet.pdf（who.int）iii癌症信息服务，日本癌症统计。

Published 2022.https://ganjoho.jp/public/qa_links/report/statistics/pdf/cancer_statistics_2023_data_E.pdfiv National Cancer Institute. What is bladder cancer? https://www.cancer.gov/types/bladder#:~:text=Types%20of%20bladder%20cancer,bladder%20cancers%20are%20urothelial%20carcinomas.v American Society of Clinical Oncology.

2022年出版。https://ganjoho.jp/public/qa_links/report/statistics/pdf/cancer_statistics_2023_data_E.pdfiv国家癌症研究所。什么是膀胱癌？https://www.cancer.gov/types/bladder#:~：text=膀胱癌的类型，膀胱癌是尿路上皮癌。v美国临床肿瘤学会。

Bladder cancer: introduction (12-2021). https://www.cancer.net/cancer-types/bladder-cancer/introduction.vi National Cancer Institute. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. .

膀胱癌：简介（12-2021）。https://www.cancer.net/cancer-types/bladder-cancer/introduction.vi国家癌症研究所。癌症统计事实：膀胱癌。https://seer.cancer.gov/statfacts/html/urinb.html.。

SOURCE ASTELLAS PHARMA INC.

阿斯特拉制药公司。