Pembrolizumab

点击上方蓝字 关注我们 编者按：2026浦江泌尿肿瘤学术大会在上海召开。近年来，抗体-药物偶联物（ADC）、免疫治疗和精准检测等创新手段快速发展，尿路上皮癌的治疗目标正由短期疾病控制，进一步转向深度缓解、长期生存和全程管理。维恩妥尤单抗联合方案改变了局部晚期或转移性尿路上皮癌（LA/mUC）的一线治疗标准；与此同时，如何在真实临床中做好患者筛选、规范用药、不良反应管理、疗效复评和长期随访，成为决定循证获益能否充分落地的关键。《肿瘤瞭望·泌尿时讯》特邀复旦大学附属肿瘤医院叶定伟教授，围绕一线治疗变革、规范持续治疗及围术期研究进展，分享临床观察与实践思考。 01 近年来，泌尿肿瘤诊疗从以手术、化疗等传统手段为主，逐步进入免疫治疗、ADC和精准检测协同发展的阶段。站在临床一线，您如何判断这一轮变革的核心特征？哪些进展最有可能转化为患者的长期获益？ 叶定伟 教授 复旦大学附属肿瘤医院 近年来，泌尿系统肿瘤诊疗正在从以手术、放疗和传统化疗为主的模式，逐步走向局部治疗与系统治疗协同、多学科参与及全程管理。 这一变化主要体现在三个方面，第一，系统治疗不断前移，临床目标不再局限于晚期阶段的肿瘤控制，而是进一步关注复发风险降低和长期结局改善。第二，ctDNA、MRD及分子标志物等技术持续发展，为风险分层和个体化决策提供了新的工具。第三，临床管理开始贯穿治疗前评估、治疗实施、不良反应管理、疗效复评和长期随访，治疗的规范性与连续性越来越重要。 尿路上皮癌是这一轮变革表现较为突出的领域之一。基于高级别循证证据，维恩妥尤单抗联合方案已经改变LA/mUC的一线治疗标准；围术期相关Ⅲ期研究也在进一步拓展我们对其临床价值的认识。但研究证据最终能否转化为患者获益，仍有赖于适宜患者选择、规范用药、不良反应管理和长期随访。 02 近年来，尿路上皮癌治疗进展迅速，临床选择从相对有限走向新药和联合方案不断涌现。您认为近几年最具里程碑意义的进展有哪些？哪些突破真正推动了临床实践走向更加积极、精准的全程管理？ 叶定伟 教授 复旦大学附属肿瘤医院 长期以来，含铂化疗是LA/mUC的一线治疗基础。近几年最具里程碑意义的研究当属EV-302研究。EV-302研究的价值，首先体现在PFS和OS两项关键终点同步改善。中位随访2.5年的数据显示，与含铂化疗相比，维恩妥尤单抗联合方案的中位PFS和中位OS均实现翻倍；泛亚洲亚组CR率达41.1%。延长随访至 3.5 年，总生存优势仍持续稳定。更值得关注的是，在维恩妥尤单抗联合方案已确认达到CR的患者中，66.2%初始为PR，并在后续治疗及观察过程中进一步达到CR。3.5年随访显示，PR转CR患者与全部CR患者的长期OS率相近。这提示，早期PR不一定代表疗效已经达到平台；对于持续获益且能够耐受的患者，应结合疗效评估与安全性管理，个体化判断后续治疗。基于这些高级别证据，国内外指南已将维恩妥尤单抗联合方案纳入一线优先或高级别推荐，使其成为当前重要的一线标准治疗选择。 不过，正确选择方案只是第一步，规范管理和治疗连续性同样重要。3.5年随访未观察到新的安全性信号，但长期治疗仍需做好基线评估、不良反应早期识别与规范干预，并根据患者耐受情况合理调整剂量或阶段性停药。通过疗效复评和安全性管理动态平衡，才能使循证获益更充分地转化为患者的长期获益。 03 随着越来越多创新药物进入临床，尿路上皮癌治疗已不再是简单增加一种药物，而是在重塑一线、后线乃至围术期治疗的整体布局。结合复旦肿瘤的临床实践，您认为未来治疗模式还将发生哪些重要变化？中国临床医生应如何将国际循证证据转化为更适合中国患者的精准治疗策略？ 叶定伟 教授 复旦大学附属肿瘤医院 未来尿路上皮癌治疗将更加重视不同疾病阶段之间的有序衔接，系统治疗、手术和术后风险管理将不再彼此割裂。EV-303和EV-304两项Ⅲ期研究分别在不同顺铂适用状态的肌层浸润性膀胱癌患者中，对维恩妥尤单抗联合方案的围术期治疗价值进行了探索。相关研究结果进一步丰富了围术期系统治疗的循证证据，也为不同患者人群的治疗选择和全程管理提供了新的研究方向。需要强调的是，围术期治疗强调新辅助治疗、根治性手术和术后治疗的完整路径，不能因为患者在术前获得临床缓解而简单省略手术或其他必要治疗环节。 同时，围术期相关探索仍应基于具体研究人群、研究方案和证据边界进行解读，临床应用需遵循已获批适应症及现行诊疗规范。未来还需要进一步明确患者筛选、治疗疗程、手术衔接、不良反应管理及生物标志物指导等问题。 对于中国临床实践而言，我们既要及时吸收国际高级别证据，也要重视中国患者的疾病特征、基础状况、治疗意愿和药物可及性。通过多学科协作，建立从患者评估、规范用药、毒性管理到手术衔接和长期随访的完整路径，才能使研究证据真正转化为可落地、可持续的中国实践。 总结 维恩妥尤单抗联合方案已经重塑LA/mUC一线治疗格局，围术期相关Ⅲ期研究也为尿路上皮癌全程管理提供了新的循证探索。叶定伟教授强调，创新方案的价值不仅体现在高级别研究证据，更取决于临床能否通过患者评估、规范用药、不良反应管理、疗效复评和长期随访，将循证获益真正转化为患者获益。面向未来，临床实践应在获批适应症和诊疗规范框架内，进一步加强多学科协作，结合生物标志物与中国患者特征，持续完善规范、连续、个体化的全程管理路径。 ▌参考文献： [1]POWLES T, VALDERRAMA B P, GUPTA S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer[J]. The New England Journal of Medicine, 2024, 390(10): 875-888. DOI: 10.1056/NEJMoa2312117.(EV-302／KEYNOTE-A39，NCT04223856) [2] POWLES T B, VAN DER HEIJDEN M S, LORIOT Y, et al. Enfortumab vedotin plus pembrolizumab in untreated locally advanced or metastatic urothelial carcinoma: 2.5-year median follow-up of the phase III EV-302/KEYNOTE-A39 trial[J]. Annals of Oncology, 2025, 36(10): 1212-1219. DOI: 10.1016/j.annonc.2025.05.536. [3] KIKUCHI E, VAN DER HEIJDEN M S, VALDERRAMA B P, et al. Pan-Asian subgroup analysis of EV-302/KEYNOTE-A39: a phase 3 study to evaluate enfortumab vedotin and pembrolizumab in patients with untreated advanced urothelial carcinoma[J]. International Journal of Clinical Oncology, 2026, 31(3): 436-446. DOI: 10.1007/s10147-025-02950-8. [4] POWLES T, VAN DER HEIJDEN M S, BEDKE J, et al. Enfortumab vedotin plus pembrolizumab versus chemotherapy for previously untreated locally advanced or metastatic urothelial carcinoma: 3.5-year follow-up and response analyses from the phase 3 EV-302 study[J]. Journal of Clinical Oncology, 2026, 44(16_suppl): 4507. DOI: 10.1200/JCO.2026.44.16_suppl.4507. [5] VULSTEKE C, ADRA N, DANCHAIVIJITR P, et al. Perioperative enfortumab vedotin and pembrolizumab in bladder cancer[J]. The New England Journal of Medicine, 2026, 394(13): 1257-1269. DOI: 10.1056/NEJMoa2511674.（EV-303／KEYNOTE-905，NCT03924895） [6] GALSKY M D, VALDERRAMA B P, MARUZZO M, et al. Enfortumab vedotin and pembrolizumab in cisplatin-eligible bladder cancer[J]. The New England Journal of Medicine, 2026, 395(4): 338-348. DOI: 10.1056/NEJMoa2601486.（EV-304／KEYNOTE-B15，NCT04700124） 中国获批适应症声明： 备思复（注射用维恩妥尤单抗）在中国获批适应症为：本品联合帕博利珠单抗用于局部晚期或转移性尿路上皮癌成人患者。本品用于既往接受过含铂化疗和程序性死亡受体-1(PD-1)或程序性死亡配体-1(PD-L1)抑制剂治疗的局部晚期或转移性尿路上皮癌成人患者。 叶定伟 教授 复旦大学附属肿瘤医院 复旦大学附属肿瘤医院副院长，泌尿外科学科带头人，泌尿肿瘤MDT首席专家 上海市泌尿肿瘤研究所所长 复旦大学前列腺肿瘤研究所所长 中国抗癌协会男性生殖系统肿瘤专委会（CACA-GO）主任委员 中国初级卫生保健基金会泌尿外科专委会主任委员 中国临床肿瘤学会（CSCO）前列腺癌专委会前任主任委员 中国抗癌协会泌尿男生殖系肿瘤专委会（CACA-GU）前任主任委员 上海市抗癌协会泌尿肿瘤专委会主任委员 NCCN前列腺癌、肾癌和膀胱癌亚洲诊治共识专家委员会委员 晚期前列腺癌圣加仑共识专家委员会委员 亚太前列腺癌学会（APPS）前任主任委员 亚太冷冻外科学会副会长 国际膀胱癌协作组（IBCG）中国代表 MAT-CN-PAD-2026-00231 Preparation date: 2026/8/23 仅供医学卫生专业人士阅读 （来源：《肿瘤瞭望-泌尿时讯》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

CS2009 Achieved Key Clinical Validations for Efficacy and Safety As of August 2026, updated data further confirmed the favorable safety profile of CS2009 and demonstrated strengthened efficacy across multiple key cohorts compared with the data presented at ASCO in May 2026. With expanded patient enrollment and longer follow-up, improvements were observed in both the objective response rate (ORR) and duration of response (DOR): Compelling monotherapy efficacy in first-line non-small cell lung cancer (NSCLC) At the 30 mg/kg dose level, CS2009 achieved an ORR of 100% and a disease control rate (DCR) of 100% in patients with PD-L1 TPS ≥50%. In the broader PD‑L1 TPS ≥1% population, the ORR was 70.8% and DCR was 91.7%. Monotherapy efficacy in Immunotherapy (IO)-pretreated NSCLC and IO-nonresponsive "cold tumors" further validates CTLA-4 activity and efficacy. In second-line NSCLC patients (all previously treated with IO plus chemotherapy), CS2009 monotherapy (30 mg/kg dose level) yielded an ORR of 38.5% and a DCR of 84.6%; In patients with heavily pretreated metastatic colorectal cancer (mCRC), CS2009 monotherapy (30 mg/kg dose level) achieved an ORR of 20% and a DCR of 93.3%; In patients with heavily pretreated soft tissue sarcoma (STS) and non-clear cell renal cell carcinoma (nccRCC), CS2009 monotherapy delivered ORR of 38.5% and 42.9%, respectively. CStone will present additional more mature Phase I/II clinical data for CS2009 in patients with advanced NSCLC and mCRC via two rapid oral presentations at ESMO 2026 in October. The Company also expects to reach consensus with global regulatory authorities including the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA), on the global Phase III registrational trial protocol in the fourth quarter of 2026. Pralsetinib Delivers Strong Sales Growth Following its effective inclusion in the National Reimbursement Drug List (NRDL) on January 1, 2026, pralsetinib's in-market sales volume increased by almost 500% year-over-year in the seven‑month period ending July 2026. Solid Cash Position As of June 30, 2026, cash and cash equivalents and time deposits totaled RMB1,560.2 million. SUZHOU, China, Aug. 31, 2026 /PRNewswire/ -- CStone Pharmaceuticals ("CStone," HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, immunology, inflammation, and other key disease areas, today announced its 2026 interim results and recent business highlights. Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, commented, "In the first half of 2026, CStone entered a pivotal stage of transition from innovation-driven accumulation to global value realization. Our lead asset, CS2009, continues to advance rapidly through global clinical development. To date, we have accumulated clinical data from more than 300 patients, consistently demonstrating three key clinical validations: first, proof of safety; second, multidimensional confirmation of CTLA‑4 target activity and efficacy, evidenced by pharmacodynamic biomarkers and clinical activity in "cold tumors" and IO‑pretreated NSCLC; and third, broad‑spectrum and highly competitive antitumor efficacy across multiple tumor types. The most recent data show that CS2009's antitumor activity continues to deepen and strengthen with longer follow-up, exhibiting particularly competitive efficacy and a well-tolerated safety profile in key patient populations, including NSCLC and mCRC. These robust data provide strong support for the upcoming global Phase III registrational trials. We look forward to presenting additional more mature clinical data on CS2009 in oral presentations at the ESMO Congress this October. Beyond CS2009, other Pipeline 2.0 candidates are also progressing steadily toward clinical stage. CS5007, built on our proprietary ADC platform, has initiated a global Phase I clinical trial in both China and Australia. In addition, more than ten early-stage programs spanning next-generation ADCs, immunology & inflammation and other areas are advancing smoothly. The successive entry of these differentiated innovative assets into clinical development will serve as a critical driver for the Company's sustained growth and global expansion. On the commercial front, our three key products, sugemalimab, pralsetinib, and avapritinib, continued to achieve breakthroughs across domestic and international markets, contributing significant momentum to revenue growth. Notably, following pralsetinib's first-time inclusion in the NRDL earlier this year, its in-market sales volume increased by almost 500% year-over-year during the first seven months of 2026, making it the primary driver of the Company's revenue growth in the first half of 2026. Looking ahead, CStone will focus on advancing the clinical value of its Pipeline 2.0 assets and actively pursue global partnerships to accelerate their development. Concurrently, the Company will continue to maximize the commercial potential of its marketed products through strategic partnerships and resource integration. Our goal is to foster a sustainable growth model where R&D and commercialization reinforce each other, creating a virtuous cycle between innovation and business operations." Clinical Stage Core Asset CS2009, PD-1/VEGF/CTLA-4 trispecific antibody - Accelerating global clinical development toward Phase III registrational trials by year end The ongoing global Phase I/II trial has enrolled more than 300 patients across China and Australia, with U.S. Investigational New Drug (IND) clearance obtained in February 2026. CStone plans to initiate the first wave of global Phase III multi-regional clinical trials (MRCTs) for CS2009 by the end of 2026. Planned registrational studies include first-line non-small cell lung cancer (NSCLC) in combination with chemotherapy (versus pembrolizumab plus chemotherapy), and first-line mCRC in combination with chemotherapy (versus bevacizumab plus chemotherapy), with additional registrational studies planned for 2027 and following years. - CS2009 validates its potential as a next-generation I/O backbone At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, CStone presented comprehensive Phase I/II data from the ongoing global multicenter trial. As of the data cutoff date of August 2026, updated monotherapy efficacy data from the ongoing global Phase I/II trial of CS2009, reflecting a longer follow-up and larger sample size than the ASCO 2026 presentation continued to demonstrate robust and deepening antitumor activity across multiple tumor types. Three important key clinical validations are achieved from over 300 patient data: Proof of safety Across all dose levels, no dose-limiting toxicities (DLTs) were observed, and the maximum tolerated dose (MTD) was not reached. In the ASCO 2026, the incidence of Grade ­3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) were 24.6% and 12.7%, respectively. Notably, the incidence of Grade ­3 VEGF-related TRAEs was only 5.1%. No excessive toxicities typically associated with CTLA-4/PD-(L)1 combinations were observed. As of August 2026, the safety profile of CS2009 remained consistent with that presented at the 2026 ASCO Annual Meeting, with no new safety signals identified. Proof of CTLA-4 activities and efficacy Dose-dependent upregulation of ICOS on CD4+ T cells was observed as a pharmacodynamic biomarker of CTLA-4 blockade. Activity was also seen in "cold tumor" not sensitive to PD-(L)1 mAb: Later-line monotherapy for mCRC (30 mg/kg): the objective response rate (ORR) was 20.0% (3/15) and the disease control rate (DCR) was 93.3% (14/15). Later-line monotherapy for soft-tissue sarcoma (STS): the ORR was 38.5% (5/13) and the DCR was 69.2% (9/13). Later-line monotherapy for non-clear cell renal cell carcinoma (nccRCC): the ORR was 42.9% (3/7) and the DCR was 100.0% (7/7). Promising anti-tumor activity in later-line post immuno-oncology (IO) NSCLC monotherapy: ORR was 23.8% (5/21), DCR was 61.9% (13/21). Among patients who had previously received immunotherapy plus platinum-based chemotherapy (n=13), ORR was 38.5% (5/13) and DCR was 84.6% (11/13). Proof of broad efficacy Monotherapy and chemo-combination activity in first-line and later-line NSCLC: First-line NSCLC monotherapy (PD-L1 tumor proportion score [TPS]­ ≥1%; enrollment completed): ORR of 61.7% (29/47) and DCR of 93.6% (44/47), including ORR of 70.8% (17/24), DCR 91.7% (22/24) in patients treated at 30 mg/kg; in the PD-L1 TPS ≥­50% group (n=24), ORR was 83.3% (20/24) and DCR was 95.8% (23/24) (versus ORR of 81.3% [13/16] at the 2026 ASCO cutoff), including ORR of 100.0% (11/11) and DCR of 100.0% (11/11) in patients treated at 30 mg/kg. After median follow up of 6 months, median progression-free survival (PFS) and DOR have not been reached. Second-line or later NSCLC monotherapy (30 mg/kg): ORR of 28.0% (7/25) and DCR of 60.0% (15/25), with a 6-month DOR rate of 83.3% (versus ORR of 24.0% and a 6-month DOR rate of 80.0% at the 2026 ASCO cutoff). Across all evaluated dose levels (n=54), ORR was 16.7% (9/54) and DCR was 68.5% (37/54), with a 6-month DOR rate of 87.5% (versus 85.7% at the 2026 ASCO cutoff). Later-line NSCLC (second/third-line combination therapy, n=6): ORR of 66.7% (4/6), DCR of 100.0% (6/6). Data are as of the 2026 ASCO data cutoff and will be updated at ESMO 2026. First-line squamous NSCLC combination therapy (PD-L1-low/negative, TPS ≤5%, n=8): ORR of 75.0% (6/8), DCR of 100.0% (8/8); notably, the ORR reached 100.0% (4/4) in the PD-L1-negative subgroup. Data are as of the ASCO 2026 data cutoff and will be updated at ESMO 2026. Robust Chemo-combo efficacy in the first-line mCRC, mostly proficient mismatch repair or microsatellite stable (pMMR/MSS): First-line mCRC (with XELOX, n=6): ORR of 66.7% (4/6), DCR of 100.0% (6/6). Data as of 2026 ASCO cutoff, will be updated at ESMO 2026. Promising monotherapy activity observed in metastatic castration-resistant prostate cancer (mCRPC), ovarian cancer, triple-negative breast cancer, gastric cancer, esophageal cancer, as well as STS and nccRCC. - Upcoming two oral presentations of CS2009 at ESMO 2026 The clinical research results of CS2009 have been accepted for two Rapid Oral presentations at the 2026 European Society for Medical Oncology (ESMO) Congress. The presentations will feature Phase I/II clinical data of CS2009 in patients with advanced NSCLC and mCRC. Other Clinical Stage Asset CS5007, EGFR/HER3 ADC - Global Phase I trial initiated in China and Australia The Company initiated the Phase I first-in-human study in June 2026. This trial consists of dose-escalation and dose-expansion cohorts evaluating CS5007 as a monotherapy in patients with advanced solid tumors, and will be conducted concurrently in Australia and China. CStone presented preclinical data for CS5007 at the 2026 American Association for Cancer Research (AACR) Annual Meeting, further supporting its broad-spectrum anti-tumor potential. Preclinical/IND-enabling Stage Programs A balanced, differentiated early-stage portfolio spanning oncology and immunology/inflammation CStone's preclinical Pipeline 2.0 comprises innovative candidates across multispecific antibodies, ADCs and other next-generation modalities, with potential first FIC or BIC opportunities spanning oncology, immunology, inflammation and other high-value therapeutic areas. The Company's proprietary ADC platform incorporates optimized linker technologies designed to enable tumor-selective payload release and supports multiple Pipeline 2.0 ADC candidates, including CS5007 (EGFR and HER3 bispecific ADC), CS5006 (ITGB4 ADC), CS5008 (DLL3 and SSTR2 bispecific ADC), etc. The Company is also exploring next-generation ADC technologies, including dual-payload ADCs (e.g., CS5009, a B7H3/PD-L1 bispecific dual-payload ADC, and CS5010, a HER2-targeting dual-payload ADC) and novel-payload ADCs (e.g., CS5012, a HER2-targeting novel-payload ADC). In April 2026, CStone presented preclinical data for CS5007, CS5006 and CS5008 at the 2026 AACR Annual Meeting, highlighting the breadth and differentiation of its next-generation ADC pipeline. Beyond oncology, CStone has expanded Pipeline 2.0 into immunology and inflammation by leveraging its proprietary multispecific antibody platform. The Company has developed CS2015 (OX40L/TSLP bispecific antibody) targeting Type 2 inflammatory diseases, CS2013 (BAFF/APRIL bispecific antibody) targeting B cell-mediated autoimmune diseases, CS2016 (TL1A/α4β7 bispecific antibody), and CS1016 (PD-1 agonist antibody). Future and Outlook Our mission is to deliver transformative therapies through scientific excellence and technological innovation, making high-quality treatments accessible worldwide to benefit patients and their families. We reaffirm our commitment to advancing a robust and differentiated pipeline by prioritizing internal discovery capabilities and sustained R&D investments, while executing strategic partnerships to unlock the global value of our in-market products. Key catalysts for the second half of 2026 include: Clinical milestones Accelerate global development of CS2009 by advancing interactions with global regulatory authorities, including the U.S. FDA and the CDE of NMPA, on Phase III registrational trial design, with the first wave of global Phase III MRCTs planned to be initiated by the end of 2026, while continuing to pursue global partnerships. Advance clinical development of CS5007 (EGFR/HER3 bispecific ADC), CS5006 (ITGB4 ADC), CS5008 (SSTR2/DLL3 ADC) and other early-stage candidates. Innovation and technology Further strengthen proprietary technology platforms, including multi-specific antibody and next-generation ADC technologies, to support sustained expansion of the preclinical pipeline. Present key clinical data, including updated CS2009 data, at major international scientific conferences, including two Rapid Oral presentations of CS2009 Phase I/II data at the 2026 ESMO Congress. 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