Pembrolizumab/Hyaluronidase

美国FDA已授予免疫治疗药物帕博利珠单抗（Keytruda）及其皮下注射剂型（Keytruda Qlex）联合抗体偶联药物恩诺单抗（Padcev）的补充生物制剂许可申请优先审评资格。这意味着该联合疗法有望在2026年8月17日前获得批准，用于可接受顺铂化疗的MIBC患者的围手术期治疗。肌层浸润性膀胱癌：为何亟需更优方案？ 膀胱癌是全球常见的恶性肿瘤之一，其中约25%的患者初诊即为肌层浸润性膀胱癌（MIBC）。这类肿瘤已经侵犯到膀胱肌层，具有较高的侵袭性和转移风险。传统标准治疗是顺铂联合吉西他滨的新辅助化疗，随后进行根治性膀胱切除术，术后根据情况辅以化疗。然而，即便经过这样“最大努力”的治疗，仍有相当比例的患者会出现疾病进展或生存期受限。因此，医学界一直在探索更有效、更安全的治疗方案。新组合疗法：免疫治疗“牵手”ADC 本次获得优先审评的组合方案包括两种药物： 帕博利珠单抗（Keytruda）：一种PD-1免疫检查点抑制剂，通过“唤醒”患者自身的免疫系统来攻击癌细胞。 恩诺单抗（Padcev）：一种抗体偶联药物（ADC），它能精准识别膀胱癌细胞表面的Nectin-4蛋白，并将化疗毒素直接投递到癌细胞内部。 两者联用，一个负责解除免疫“刹车”，一个负责定向“爆破”，产生了协同增效的抗肿瘤效果。 此外，FDA同时审评了皮下注射剂型Keytruda Qlex。与需要静脉输注的传统帕博利珠单抗相比，皮下注射可在几分钟内完成，大幅缩短治疗时间，提高患者便利性。关键研究数据：疗效显著优于标准化疗 此次申请主要基于名为KEYNOTE-B15/EV-304的III期临床试验。该研究纳入了808名适合顺铂化疗的MIBC患者，随机分为两组：一组接受恩诺单抗联合帕博利珠单抗（新辅助4周期+术后辅助治疗），另一组接受传统的顺铂+吉西他滨化疗（新辅助4周期+术后观察）。 结果令人瞩目： 无事件生存期（EFS）：组合疗法组的中位EFS尚未达到（意味着超过一半的患者在随访期内未出现疾病进展或死亡），而化疗组为48.5个月。组合治疗使疾病进展或死亡风险降低了47%（HR=0.53），差异具有高度统计学显著性。 24个月EFS率：组合疗法组为79.4%，化疗组为66.2%——这意味着在两年时，组合疗法组有近八成患者疾病未进展，高出化疗组13个百分点。 总生存期（OS）：虽然两组的中位OS均尚未达到，但组合疗法将死亡风险降低了35%（HR=0.65）。24个月OS率分别为86.9%和81.3%。 病理完全缓解率（pCR）：在接受新辅助治疗后切除的肿瘤组织中，组合疗法组有55.8%的患者找不到任何癌细胞（病理完全缓解），而化疗组仅为32.5%。两者相差23.4个百分点。安全性：与已知风险一致，总体可控 在副作用方面，联合方案组的任何级别治疗相关不良事件发生率为98.0%，与化疗组的98.2%相当。3级及以上严重不良事件的发生率略高（75.7% vs 67.2%），但研究人员指出，这些安全性特征与两种药物既往联用经验一致，临床上是可管理的。已有先例：顺铂不耐受患者的获批 值得注意的是，这并不是恩诺单抗联合帕博利珠单抗在MIBC领域的首次突破。2025年11月，FDA已批准该组合用于不适合顺铂化疗的MIBC患者（新辅助+辅助治疗）。此外，该组合也已被批准用于局部晚期或转移性尿路上皮癌（无论顺铂适用性如何）。 此次优先审评旨在将适应症扩展至适合顺铂化疗的MIBC患者。如果获得批准，这意味着几乎所有可手术的肌层浸润性膀胱癌患者，无论是否能够耐受顺铂，都将有机会接受这一更有效的联合治疗方案。展望未来 FDA已将目标审评完成日期定为2026年8月17日。如果顺利获批，这一“免疫+ADC”的强效组合将成为肌层浸润性膀胱癌围手术期治疗的新标准，为患者带来更高的治愈希望和更长的生存时间。 膀胱癌研究精选及新进临床试验 肿瘤研究前沿（167）：ctDNA在膀胱癌治疗中的“双面性”：能预警远处转移，却难捕捉局部复发 肿瘤研究前沿（151）：新药联合疗法为膀胱癌患者提供“保膀胱”新选择 肿瘤研究前沿（148）：5年数据分析显示辅助免疫治疗为高危膀胱癌患者带来持久获益 肿瘤研究前沿（117）：新疗法让无法化疗的膀胱癌患者获得“根治”新希望 肿瘤研究前沿（七十）：TARA-002在初治膀胱癌患者中展现高缓解率与良好安全性 序号 临床试验名称 纳入标准（核心摘录） 开展区域 1 QL1706治疗既往接受含铂化疗、PD-(L)1抑制剂和经或未经ADC治疗的不可切除局部晚期或转移性尿路上皮癌的有效性与安全性：一项前瞻性、单中心、单臂、开放标签的II期临床研究 1.经组织病理学证实为局部晚期或转移性尿路上皮癌（膀胱、输尿管、肾盂或尿道来源）；具有尿路上皮癌合并鳞状上皮分化或混合细胞类型的受试者，仍符合入组条件； 2.受试者在基线时具有影像学证实的转移性或局部晚期疾病。其中，局部晚期疾病患者，根据治疗医生的意见，无法以根治为目的进行切除； 3.受试者在诊断局部晚期或转移性疾病期间或之后，曾接受过免疫检查点抑制剂、和含铂方案化疗（顺铂或卡铂）治疗；且疾病在最近一次治疗期间或结束后6个月内进展（影像学证实）；允许接受过≤1种抗体偶联药物（ADC）治疗； 中山大学肿瘤防治中心 2 一项评估放疗联合特瑞普利单抗与9MW2821联合特瑞普利单抗新辅助治疗在上尿路尿路上皮癌（UTUC）患者中安全性和有效性的开放、单中心、随机对照Ⅱ期临床研究 1.经组织病理学确认的上尿路尿路上皮癌（包括肾盂癌和输尿管癌），伴有鳞状分化、腺分化或混合类型（混合类型中尿路上皮癌成分需 > 50%）的尿路上皮癌也符合要求；2.经影像学确认的非转移性尿路上皮癌（M0），临床分期为 T1-3NxM0；经评估受试者可耐受并计划行根治性手术，且临床评估可耐受放疗； 北京大学第三医院 3 基于SHR-1811的联合方案治疗晚期HER2高表达尿路上皮癌的有效性与安全性的单中心、多队列、探索性研究 1.经组织学或细胞学确诊为不可手术切除/转移性晚期尿路上皮癌，Her-2免疫组化2+及以上表达阳性； 2.在晚期或转移性阶段，接受过一线标准治疗失败或不耐受。有经研究者确认的最近一次治疗期间或之后肿瘤疾病进展的影像学证据或治疗期间出现的药物不耐受证据； 安徽医科大学第一附属医院 4 基于内镜下激光消融联合维恩妥尤与特瑞普利治疗局限性高危上尿路尿路上皮癌的II期临床研究 1.组织或细胞学确诊 UTUC，临床分期cTa-2N0M0； 2.存在至少一项高危特征（多灶、高级别、影像疑肌层侵袭、同侧肾积水、既往膀胱高级别尿路上皮癌、变异组织学 >=50%、肿瘤<=20 mm 或可降至 <=20 mm）； 3.具备保肾适应症：单肾、双侧病变、慢性肾病、合并症限制RNU或患者强烈保肾意愿； 四川大学华西医院

Submission based on statistically significant event-free and overall survival data from the Phase 3 EV-304 trial Building on the existing indication in cisplatin-ineligible muscle-invasive bladder cancer (MIBC), if approved, this regimen would be the first and only perioperative treatment for patients with MIBC regardless of cisplatin eligibility, marking a potential new standard of care April 20, 2026 -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") and Pfizer Inc. (NYSE: PFE) announced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review a supplemental Biologics License Application (sBLA) for perioperative (before and after surgery) PADCEV™ (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, in combination with the PD-1 inhibitor Keytruda® (pembrolizumab) or Keytruda QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) as treatment for patients with muscle-invasive bladder cancer (MIBC). This regimen was FDA-approved in November 2025 for use as perioperative treatment in cisplatin-ineligible patients with MIBC. This filing seeks to expand the indication to patients with MIBC regardless of cisplatin eligibility. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where limited therapy options exist.i Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of August 17, 2026. Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas "The data from the EV-304 trial take us another step closer to bringing perioperative enfortumab vedotin plus pembrolizumab to patients with muscle-invasive bladder cancer regardless of cisplatin eligibility, who still face a recurrence rate of more than fifty percent despite curative-intent surgery, highlighting the ongoing need for improved treatment strategies." Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer "For people with muscle‑invasive bladder cancer, surgery is often just the beginning of a long and uncertain journey, with far too many patients seeing their cancer return. If approved, perioperative PADCEV plus pembrolizumab could meaningfully change that experience, potentially helping patients reduce the risk of recurrence and live longer, regardless of whether they are eligible for cisplatin." The sBLA submission was based on data from the Phase 3 EV-304 clinical trial (also known as KEYNOTE-B15), evaluating perioperative enfortumab vedotin in combination with pembrolizumab in patients with MIBC eligible for cisplatin-containing chemotherapy. Results from EV-304, presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), showed a 47% reduction in the risk of tumor recurrence, progression or death and a 35% reduced risk of death for perioperative enfortumab vedotin in combination with pembrolizumab compared to standard of care neoadjuvant (before surgery) gemcitabine and cisplatin chemotherapy.ii The combination also demonstrated a pathological complete response (pCR) rate of 55.8% compared with 32.5% pCR rate in the chemotherapy arm at the time of surgery.ii The safety profile for perioperative enfortumab vedotin plus pembrolizumab observed in EV-304 was consistent with prior experience with the combination and there were no new safety signals.ii These data will be discussed with additional global health authorities for potential regulatory filings. The EV-304 trial is an ongoing, open-label, randomized, controlled, Phase 3 study evaluating perioperative enfortumab vedotin in combination with pembrolizumab versus neoadjuvant chemotherapy (gemcitabine and cisplatin) in patients with MIBC who are eligible for cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant (before and after surgery) enfortumab vedotin in combination with pembrolizumab (arm A) or neoadjuvant chemotherapy (arm B). Curative-intent surgery (cystectomy) was performed in both arms. Enfortumab vedotin in combination with pembrolizumab was administered as a planned total of 9 cycles of enfortumab vedotin and 17 cycles of pembrolizumab split before and after surgery.iii The primary endpoint of this trial is EFS, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) or failure to undergo RC in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause. Key secondary endpoints include OS and pCR rate.iii Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 people each year globally, including an estimated 85,000 people in the U.S.iv,v MIBC represents approximately 30% of all bladder cancer cases.vi The standard treatment for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery.vii However, even after undergoing surgery, half of patients with MIBC experience disease recurrence.viii PADCEV™ (enfortumab vedotin-ejfv) 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.ix 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 result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).x PADCEV plus pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) in the United States, the European Union, Japan and a number of other countries around the world. PADCEV is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.x Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world's most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. Seagen and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen's and Astellas' PADCEV™ (enfortumab vedotin) and Merck's Keytruda® (pembrolizumab) in patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. 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). i Priority Review. US FDA. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed February 24, 2026. ii Neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab for participants with muscle-invasive bladder cancer who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. Abstract #LBA630. 2026 American Society of Clinical Oncology Genitourinary (ASCO GU) Congress. iii National Institute of Health. National Library of Medicine. Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304) (KEYNOTE-B15). ClinicalTrials.gov identifier: NCT04700124. Published January 7, 2021. Updated August 26, 2025. Accessed February 24, 2026. Available at: https://www.clinicaltrials.gov/study/NCT04700124. iv World Bladder Cancer Patient Coalition. GLOBOCAN 2022: Bladder cancer 9th most common worldwide. Accessed February 24, 2026. Available at: https://worldbladdercancer.org/news_events/globocan-2022-bladder-cancer-is-the-9th-most-commonly-diagnosed-worldwide/ v American Cancer Society. Cancer Facts & Figures 2025. Accessed February 24, 2026. Available at: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2025-cancer-facts-figures.html vi Bladder Cancer Awareness Network. What is Muscle Invasive Bladder Cancer? Accessed February 24, 2026. Available at: https://bcan.org/what-is-muscle-invasive-bladder-cancer/#:~:text=When%20tumors%20grow%20into%20or,Virginia%20Health%20System%20explain% 20MIBC vii Funt SA, Rosenberg JE. Systemic, perioperative management of muscle-invasive bladder cancer and future horizons. Nat Rev Clin Oncol. 2017 Apr;14(4):221-234. doi: 10.1038/nrclinonc.2016.188. Epub 2016 Nov 22. PMID: 27874062; PMCID: PMC6054138. viii Squires P, Cook EE, Song Y, Wang C, Zhang A, Seshasayee SM, Rogiers A, Li H, Mamtani R. Treatment Patterns, Disease Recurrence, and Overall Survival in Patients with Muscle-Invasive Bladder Cancer after Radical Cystectomy: A Population-Level Claims-Based Analysis. Clinical Genitourinary Cancer. 2025 Nov;102466. https://doi.org/10.1016/j.clgc.2025.102466. ix Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13. x PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc. The content above comes from the network. if any infringement, please contact us to modify.