A Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)

This is a Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk Non-Muscle-Invasive Bladder Cancer.

开始日期2024-09-16

申办/合作机构

CG Oncology, Inc.

NCT06253845

/ Recruiting临床1期IIT

A Phase 1b, Single Arm Study of CG0070 After Transurethral Resection in Patients With Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC)

Investigators will evaluate the safety of CG0070 for the treatment of patients with Intermediate-Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC).

开始日期2024-03-01

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

NCT06111235

/ Recruiting临床3期

A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec Versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT)

This is a Phase 3, open-label, randomized trial designed to evaluate the RFS of TURBT followed by cretostimogene grenadenorepvec versus TURBT followed by observation for the treatment of participants with IR-NMIBC.

开始日期2023-12-14

申办/合作机构

CG Oncology, Inc.

100 项与 Cretostimogene Grenadenorepvec 相关的临床结果

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100 项与 Cretostimogene Grenadenorepvec 相关的转化医学

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100 项与 Cretostimogene Grenadenorepvec 相关的专利（医药）

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项与 Cretostimogene Grenadenorepvec 相关的文献（医药）

2025-02-01·EXPERT OPINION ON BIOLOGICAL THERAPY

Integrating gene therapy into the treatment paradigm for non-muscle invasive bladder cancer

Review

作者: Jazayeri, Behzad ; Mokkapati, Sharada ; Steinmetz, Alexis R. ; Li, Roger ; Dinney, Colin P. ; Pierce, Morgan ; McConkey, David

INTRODUCTION:

Approximately 75% of bladder cancer cases are non-muscle invasive at diagnosis. Drug development for non-muscle invasive bladder cancer (NMIBC) has historically lagged behind that of other malignancies. No treatment has demonstrated the ability to overcome drug resistance that ultimately leads to recurrence and progression. Gene therapy is emerging as a promising option for patients with NMIBC.

AREAS COVERED:

This review summarizes the clinical application of gene therapy in NMIBC management and discusses recent clinical trials involving the adenoviral vector-based treatment nadofaragene firadenovec, and the oncolytic serotype 5 adenovirus, cretostimogene grenadenorepvec. Nadofaragene received approval by the Food and Drug Administration in December 2022, and cretostimogene has been granted Fast Track Designation and Breakthrough Therapy Designation. Ongoing trials are investigating strategies to augment efficacy and durability of these therapies.

EXPERT OPINION:

Gene therapy may overcome resistance mechanisms of other NMIBC treatments, and data suggest a role for combination therapy with additive or synergistic agents. Significant differences in trial design limit comparability of agents across trials, highlighting the need for critical assessment of published findings. While initial investigations were in high-risk patients who recur despite frontline therapy with Bacillus Calmette-Guerin (BCG), there is growing interest in BCG-naïve and intermediate-risk populations.

2025-01-01·NATURE MEDICINE

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial

Article

作者: Dinney, Colin P. N. ; Moran-Segura, Carlos M ; Anderson, Alexander R A ; Mulé, James J. ; Sexton, Wade J ; Anderson, Alexander R. A. ; Spiess, Philippe E. ; Li, Tingyi ; Conejo-Garcia, Jose R. ; Johnson, Joseph O ; Mulé, James J ; Rodriguez, Paulo C ; Dhillon, Jasreman ; Villa, Nancy Y ; Burke, James M ; Wang, Xuefeng ; Burke, James M. ; Grass, G. Daniel ; Dorman, Denise ; Pow-Sang, Julio M. ; Li, Roger ; Yu, Xiaoqing ; Powers, John J ; Moran-Segura, Carlos M. ; Jain, Rohit K. ; Borjas, Gustavo ; Sexton, Wade J. ; Rodriguez, Paulo C. ; Poch, Michael A ; Villa, Nancy Y. ; Poch, Michael A. ; Zhang, Jingsong ; Jain, Rohit K ; Powers, John J. ; Gilbert, Scott M. ; Francis, Natasha ; Gilbert, Scott M ; Dinney, Colin P N ; Grass, G Daniel ; Conejo-Garcia, Jose R ; Spiess, Philippe E ; Kim, Youngchul ; Johnson, Joseph O. ; Zemp, Logan ; Pow-Sang, Julio M

There is a critical unmet need for safe and efficacious neoadjuvant treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer. Here we launched a phase 1b study using the combination of intravesical cretostimogene grenadenorepvec (oncolytic serotype 5 adenovirus encoding granulocyte-macrophage colony-stimulating factor) with systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. The primary objective was to measure safety, and the secondary objective was to assess the anti-tumor efficacy as measured by pathologic complete response along with 1-year recurrence-free survival. No dose-limiting toxicity was encountered in 21 patients enrolled and treated. Combination treatment achieved a pathologic complete response rate of 42.1% and a 1-year recurrence-free survival rate of 70.4%. Pathologic response was associated with baseline free E2F activity and tumor mutational burden but not PD-L1 status. Although T cell infiltration was broadly induced after intravesical oncolytic immunotherapy, the formation, enlargement and maturation of tertiary lymphoid structures was specifically associated with complete response, supporting the importance of coordinated humoral and cellular immune responses. Together, these results highlight the potential of this combination regimen to enhance therapeutic efficacy in cisplatin-ineligible patients with muscle-invasive bladder cancer, warranting additional study as a neoadjuvant therapeutic option. ClinicalTrials.gov identifier: NCT04610671 .

2024-08-01·NATURE MEDICINE

Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial

Article

作者: Nam, Jong Kil ; Jacob, Joseph M ; Jung, Seung Il ; Geynisman, Daniel M ; Dickstein, Rian ; Steinberg, Gary D ; Uchio, Edward M ; Shah, Paras H ; Lamm, Donald L ; Keegan, Kirk A ; Kang, Seok Ho ; Burke, James M ; Stewart, Tyler F ; Pearce, Shane M ; Kamat, Ashish M ; Bivalacqua, Trinity J ; Meeks, Joshua J ; Li, Roger

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

147

项与 Cretostimogene Grenadenorepvec 相关的新闻（医药）

2025-03-26

·求实药社

6成患者缓解2年！乐普生物膀胱癌溶瘤病毒III临床研究更新结果

来源：药讯随说 3月24日（当地时间），CG Oncology公布其溶瘤病毒疗法Cretostimogene Grenadenorepvec单药治疗对卡介苗（BCG）无应答的高危非肌层浸润性膀胱癌（NMIBC）患者的III期临床研究（BOND-003试验）更新结果：接受单剂治疗后任何时间达到完全缓解（CR）患者比例达75.5%。中位DoR未到达且超28月。12月确认CR患者24月时确认缓解患者比例为46%（截至2025年1月20日）。 CG Oncology称此更新结果将在40届欧洲泌尿外科协会（SUO）年会中公布。 BOND-3研究（NCT04452591）为一项评估单药治疗高风险NMIBC患者的单臂III期临床研究。研究在北美和亚太地区招募入组112例伴有导管内原位癌（CIS）且伴/不伴Ta或T1乳头状肿瘤的对BCG无应答的高风险NMIBC患者。研究主要终点为任何时间的CR，次要终点为DoR。 2024年12月，公布的BOND-3顶线结果显示：单药治疗后任何时间点实现CR患者比例74.5%（82/110，95%CI：65.4%-82.4%）。中位DOR尚未达到，但根据截至2024年9月30日的数据预估中位DOR超过27个月。根据Kaplan-Meier估算，63.5%患者缓解时间≥12月，56.6%患者缓解时间≥24月。此外，97.3%患者12个月内未进展至肌层浸润性膀胱癌（MIBC），完全缓解率75%！乐普生物膀胱癌溶瘤病毒临床研究结果公布。本次公布的更新结果：接受单剂治疗后任何时间CR患者比例75.5%。中位DoR未到达且超28月。12月确认CR患者24月时确认缓解患者比例为46%（截至2025年1月20日）。12月和24月缓解患者比例分别为63.5%、58.7%。 Cretostimogene Grenadenorepvec（研发代码：CG0070）是一种膀胱内给药的溶瘤病毒疗法工程化5型腺病毒溶瘤病毒，嵌入了两种编码基因-肿瘤选择性启动子E2F-1和GM-CSF基因，经修饰后的Ad5可选择性地在Rb调控缺陷的肿瘤细胞内复制，最终裂解肿瘤细胞。破裂后的癌细胞则会进一步释放肿瘤抗原以及GM-CSF，刺激全身性抗肿瘤免疫反应，双重杀瘤作用可以将抗肿瘤活性最大化。 2019年，乐普生物获得CG0070中国大陆、香港和澳门的开发和商业化权益。2021年中国CDE批准临床试验,乐普生物在中国启动了一项I期临床研究（CTR20231376）。而在日本、韩国和中国台湾和中国之外亚洲地区的权益在2020年授给给了日本Kissei制药，该交易总额达1.4亿美元。免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部。联系我们 I-RNA 小核酸 2025 展位火热预定中！扫码立即咨询电话：13816031174 （同微信）赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。点击此处“阅读全文”咨询更多！

临床结果临床3期

2025-03-24

·Endpoints

Surrozen raises $175M, to focus on ophthalmology; CBC Group has a new $1B fund

Plus, news about CG Oncology, Opus Genetics and Valneva: Surrozen’s pivot and capital raise: The South San Francisco drug developer is scrapping clinical development in severe alcohol associated hepatitis and instead focusing on its ophthalmology pipeline. It also lined up $175 million from a private placement. Surrozen’s stock $SRZN was down about 5% on Monday morning. — Kyle LaHucik CBC Group’s $1B fund: The largest healthcare-focused asset management firm in Asia marked the first close of its healthcare buyout fund. The firm has raised $1 billion so far of a targeted $1.4 billion. It plans to support biopharma, medical devices and other healthcare companies. — Kyle LaHucik CG Oncology touts updated Phase 3 bladder cancer data: The Irvine, CA-based biotech’s oncolytic virus candidate, cretostimogene grenadenorepvec, led to complete responses in 46% of high-risk non-muscle invasive bladder cancer patients at 12 months as of the January data cutoff. The median duration of response has not yet been reached but exceeds 28 months, according to the company’s presentation at the European Association of Urology’s annual meeting. CG’s shares $CGON were up around 6% on Monday morning. — Ayisha Sharma Opus Genetics’ $21.5M raise: The North Carolina retinal biotech is getting the new funds from a public offering and a private placement. The gene therapy company, based in Research Triangle Park, NC, merged with eye drop maker Ocuphire Pharma in the fall. — Kyle LaHucik French government buys doses of Valneva’s chikungunya vaccine: The biotech will supply 40,000 doses of its chikungunya vaccine, dubbed IXCHIQ, in early April to France’s La Réunion, an island located east of Africa where cases of chikungunya, a virus spread by mosquitoes, have risen since the start of 2025, according to a release . Valneva’s stock $VALN rose nearly 7% after sharing the supply announcement. — Anna Brown

疫苗临床3期

2025-01-31

·ioncology

年度盘点丨优患所忧，及患所急！魏强教授回顾2024年膀胱癌治疗进展

- 年度盘点 - 2024年膀胱癌治疗进展魏强教授编者按：膀胱癌是常见的泌尿系统恶性肿瘤之一，严重威胁着国人生命健康。对于局限期患者而言，长期反复的膀胱腔内治疗或检查操作，使患者需要频繁住院或门诊随访；可手术患者也有长期背尿袋的“难言之隐”；而不可手术的晚期患者通过传统化疗的治疗获益较为有限。因此，无论是生存还是生活质量，膀胱癌患者都存在巨大的未被满足的治疗需求，这也是泌尿外科医生、肿瘤科医生为之探索创新的动力。值此辞旧迎新之际，《肿瘤瞭望》特邀四川大学华西医院魏强教授回顾2024年膀胱的治疗进展。这些新的研究突破，有望为膀胱癌患者带来延长生存、改善生活质量的“双赢”治疗策略。 01 NMIBC：局部和系统治疗“并蒂花开” 非肌层浸润性膀胱癌（NMIBC）是最常见的膀胱癌类型，约占初诊患者的四分之三。经尿道膀胱肿瘤切除（TURBt）是NMIBC的首选治疗[1]，但仍有约一半的患者可在1年内复发[2]。目前，国内外指南共识根据NMIBC复发进展风险和预后的不同，将其分为低危、中危、高危和极高危。针对中高危及以上患者，通常使用卡介苗（BCG）膀胱灌注免疫治疗，但仍有部分患者对BCG无反应，或无法耐药BCG相关不良反应（如膀胱炎、血尿、感染、发热等），且部分国家和地区存在BCG供应不足的情况。近年来，有诸多研究采用新的局部或系统治疗策略，以应对BCG灌注无反应问题，以及降低复发和进展风险。这些治疗策略涵盖了化疗、免疫治疗以及新型药物的膀胱腔内治疗或系统治疗。化疗免疫治疗其他新型药物多种药物联合灌注灌注剂量与频率优化 ADC类腔内灌注热灌注 BCG与化疗联合灌注 FGFR3 TKI靶向药物增加灌注频率与时长（Chemoablation） BCG与化疗序贯灌注病毒样药物偶联物（virus-like drug conjugates，VDC）持续释放（TAR200） BCG与ICI序贯治疗溶瘤腺病毒CG0070 逆温凝胶化疗灌注 BCG与ICI联合治疗 IL-15超激动剂 _ _ 免疫增强剂TARA-002 TAR-200腔内治疗 TAR-200是一种半渗透性的硅胶管状结构，可以在膀胱内持续数周连续释放化疗药物（吉西他滨）的新型给药系统。SunRISe系列研究在不同治疗场景探讨了基于TAR-200的治疗模式，如SunRISe-1和SunRISe-5是针对BCG无反应的高危NMIBC，采用TAR-200联合Cetrelimab（PD-1单抗）或者单独TAR-200、Cetrelimab治疗的II期和III期研究；SunRISe-2和SunRISe-4则是针对肌层浸润性膀胱癌（MIBC）患者，分别采用TAR-200联合Cetrelimab对比GC＋放疗的III期研究，以及采用TAR-200联合Cetrelimab新辅助治疗的II期研究；SunRISe-3则是针对初治的高危NMIBC患者，采用TAR-200或BCG灌注治疗的III期研究。 2024年ESMO大会报道了SunRISe-1研究[3]结果，针对BCG无反应的高危NMIBC的患者，队列1（TAR-200＋Cetrelimab）、队列2（TAR-200）、队列3（Cetrelimab）确认的总体CR率分别为67.9%、83.5%和46.4%；1年CR率则分别为56.7%、57.4%和22.8%。单独使用TAR-200（6%）和cetrelimab（7%）时，因治疗相关不良事件（TRAE）导致的停药率较低，而联合使用时停药率较高（TAR-200 26%或cetrelimab 23%）。未发生治疗相关死亡。这项研究初步展示了TAR-200腔内治疗具有较高的CR率和可控的安全性。 ADC系统治疗维迪西妥单抗（RC48）、维恩妥尤单抗（EV）等靶向于HER2、Nectin-4的新型ADC，已经在mUC领域一线免疫联合治疗取得突破性进展。这种“靶向化疗”药物相较于传统化疗具有增效减毒的特征。近年来，新型ADC开始拓展至局限期膀胱癌的治疗，包括针对NMIBC的系统治疗或膀胱灌注治疗。例如2023年ASCO大会报道的EV-104研究[4]，是一项正在进行的开放标签、多中心、剂量递增I期试验，该研究显示静脉注射EV用于BCG无应答的高危NMIBC患者的耐受性良好。125mg剂量时观察到了初步抗肿瘤活性，4例患者中有3例达到了CR。2024年ASCO大会也报道了RC48用于高危NMIBC患者的初步疗效数据[5]，在入组的27例患者中，有10例患者接受维迪西妥单抗、17例患者接受BCG。研究结果显示HER2过表达显著影响膀胱癌的肿瘤免疫响应；而且RC48相比BCG具有更高的1年RFS率（100% vs 58.8%）。2024年AUA大会公布的TRUCE04研究[6]，在24例肿瘤无法完全切除或无法耐受手术并且HER2中高表达（IHC 2+或3+）的NMIBC患者中，有8例患者接受了RC48单药治疗，16例患者接受了RC48联合替雷利珠单抗治疗，结果显示有16例患者达到完全缓解（CR），8例患者达到疾病稳定（SD）。 ICI灌注治疗如前所述，SunRISe系列研究中探讨了TAR-200腔内治疗单独或联合免疫检查点抑制剂（ICI）的系统治疗；当前的大多数研究也主要将ICI作为系统治疗。从理论上来看，ICI阻断PD-1/PD-L1的免疫逃逸机制，与BCG同样具有免疫激活效果，但二者是否具有协同增效作用？一项由希腊生殖和泌尿癌症协作组开展的开放标签、单臂、多中心、Ⅱ期临床试验[7]，两个阶段共入组30例高危NMIBC患者，接受度伐利尤单抗的膀胱灌注治疗。结果发现，在灌注后1年，19例可评估患者中有7例仍未出现高级别复发（1年HG-RFR：38.5%）。研究治疗结束后1、3和6个月的HG-RFR分别为70%、55%和38.5%。除局部刺激外，没有发现严重不良事件。该研究初步展现了ICI膀胱腔内治疗的抗肿瘤活性，未来仍有不少值得进一步探讨的问题，例如ICI与BCG应该进行序贯的还是联合的腔内治疗？如果序贯治疗应该先试用ICI还是BCG？ 02 MIBC：围手术期治疗“百花齐放” MIBC的标准治疗是根治性膀胱切除术，但有不少患者难以接受尿流改道带来的生活质量损害，而且部分患者仍面临术后疾病复发或进展风险。因此，MIBC围术期治疗焦点主要通过术前和/或术后治疗，达到肿瘤降期、延长保膀胱生存以及降低术后复发风险的目的。 ICI辅助和新辅助治疗 CheckMate-274研究开启了MIBC辅助免疫治疗时代，既往发表于NEJM的结果[8]显示，针对高危MIBC（未接受新辅助铂类治疗或不适合辅助铂类治疗的pT3、pT4a或pN+患者；接受过新辅助铂类治疗的ypT2至ypT4a或ypN+患者），纳武利尤单抗辅助治疗可显著改善DFS（20.8 vs 10.8个月，HR 0.70；98.22%CI：0.55~0.90；P<0.001），其总生存（OS）结果令人十分期待。2024年EAU大会上，首次报道了该研究的OS数据[9]，纳武利尤单抗组和安慰剂组的中位OS分别为69.5个月和50.1个月，死亡风险降低24%（HR 0.76，95%CI：0.61-0.96）；而PD-L1≥1%的人群中，纳武利尤单抗组的死亡风险降低44%（NR vs NR；HR 0.56，95%CI：0.36-0.86）。 AMBASSADOR研究是另一个ICI辅助治疗MIBC的III期研究。该研究入组患者为新辅助化疗后≥pT2和/或pN+/切缘阳性，以及不适合或拒绝新辅助化疗的≥pT3和/或pN+/切缘阳性患者，术后接受帕博利珠单抗或安慰剂辅助治疗1年。2024年ASCO-GU大会报道达到了研究的主要终点之一DFS：帕博利珠单抗组和对照组的中位DFS分别为29.0个月和14.0个月（HR 0.69，95%CI 0.54～0.87，P=0.001）。但另一个主要终点OS尚无显著差异（50.9 vs 55.8个月，HR 0.98，95%CI：0.76～1.26；P=0.883）[10]。 NIAGARA研究则是将免疫治疗贯穿于术前新辅助和术后辅助治疗，针对入组的顺铂耐受且计划进行根治性膀胱切除的MIBC（cT2-T4aN0/1M0）患者，试验组接受4个周期的术前度伐利尤单抗联合GC新辅助治疗，术后接受8个周期的度伐利尤单抗辅助治疗。对照组则仅接受新辅助化疗，研究的主要终点是EFS和pCR。2024年ESMO报道且同步发表于NEJM的结果显示，试验组和观察组患者的中位DFS分别为29.6个月和14.2个月（HR 0.73；95% CI，0.59~0.90；P=0.003），pCR率分别为37.3%和27.4%。但次要终点OS，目前尚未观察到显著性差异（HR，0.98；95%CI：0.17~1.26）[11]。 ADC新辅助治疗多队列、II期SURE-01研究，入组了21名不符合或拒绝接受顺铂新辅助化疗的cT2-4N0M0 MIBC患者，给予4个周期的TROP2 ADC戈沙妥珠单抗（SG）新辅助治疗，2024年ASCO报道的结果显示[12]，在11例接受根治性手术患者中，有4例（36.4%）达到了pCR。同样为多队列的II期EV-103研究，报道了队列H的结果[13]，该队列入组了顺铂不合格的MIBC（T2-T4aN0M0）患者，在术前接受3个周期的EV新辅助治疗，在可评估的患者中，pCR率为36.4%，病理降期（pDS）率为50.0%；2年EFS率为62.0%。II期RC48-C017研究[14]入组了未接受过治疗的MIBC（cT2-T4aN0-1M0）患者，术前接受6个周期的RC48联合特瑞普利单抗新辅助治疗，pCR率为61.3%（19/31）。这些研究都初步展现了ADC在MIBC新辅助治疗中的抗肿瘤活性，有较高的肿瘤降期作用。 TAR-200新辅助治疗 2024年ESMO大会报道了TAR-200用于MIBC新辅助治疗的SUNRISE-4研究[15]，入组患者术前接受4个周期的TAR-200膀胱内治疗联合Cetrelimab静脉注射治疗，或者单独Cetrelimab静脉注射治疗，然后接受根治性手术并继续术后随访。研究结果显示，TAR-200+Cetrelimab组和Cetrelimab组确认的病理完全缓解（pCR，ypT0N0）率分别为42%和23%，总体病理缓解（pOR；≤ypT1N0）率分别为60%和36%。TAR-200+cetrelimab和cetrelimab分别有72%和44%患者出现治疗相关不良事件（TRAE），其中大多为1-2级。 03 mUC：“免疫plus”涌现更多组合在转移性尿路上皮癌（mUC）领域，既往IMvigor130与KEYNOTE-361的阴性结果，为ICI联合化疗的应用蒙上一层“阴影”，但此后仍有更多免疫联合治疗模式的探索，包括联合化疗、ADC治疗以及FGFR靶向治疗等。 ICI联合化疗 ADC：后线单药，前线顺铂不耐联合免疫 FGFR：特定突变患者 IMvigor130与Keynote361均为阴性结果 EV 103 cohort A：mUC一线顺铂不耐受 EV + Pembro NORSE：mUC一线顺铂不耐受，Erda + Cetrelimab vs. Erda Checkmate 901：NIVO+GC获得阳性结果 EV 103 cohort K：mUC多重后线顺铂不耐受 THOR：mUC多重后线， Erda vs. 后线化疗 _ TROPHY-U-01：mUC多重后线，UGT1A1酶多重活性 SG单药 _ _ EV-302: mUC一线 EV+Pembro vs. Chemo _ _ RC48 C014: mUC 前/后线 RC48+PD1 _ EV-302研究：ADC＋ICI EV-302研究则是全球首个证实ADC联合免疫治疗作为mUC一线治疗并获阳性结果的III期临床试验。既往发表于NEJM的结果[18]显示，与单独化疗相比，EV＋帕博利珠单抗组的mPFS（12.5 vs. 6.3个月；HR 0.45，95%CI：0.38~0.54；P<0.001）和mOS（31.5 vs. 16.1个月；0.47，95%CI：0.38~0.58；P<0.001）均几乎延长了一倍。2024年ASCO大会进一步报道了该研究的患者报告结局（PRO）[19]。结果发现，EV＋帕博利珠单抗联合治疗并不会降低患者的生活质量和身体机能，这也进一步表明了联合治疗对于mUC的临床应用价值。而2024年ESMO Asia报道在泛亚洲亚组中，EV＋帕博利珠单抗组的PFS事件风险更是降低了70%（NE vs. 6.3个月，HR 0.30，95%CI：0.19~0.48），亚洲患者在OS方面也同样显示出更大幅度的获益趋势，死亡风险降低66%（HR 0.34，95%CI：0.18~0.65） 04 总结随着诊疗研究的深入，膀胱癌的治疗已经呈现多元化、个体化的综合治疗发展趋势，涵盖了从NMIBC到MIBC、mUC各个疾病阶段的局部治疗和系统治疗，均涌现了许多新型的治疗手段或药物。在NMIBC领域，最令人瞩目的莫过于TAR200等创新的腔内治疗手段有望促使更多的局部治疗变革；而MIBC围术期治疗无论是新辅助、辅助治疗还是保膀胱治疗，在ADC、ICI等新型药物的加持下，都产生了新的疗效飞跃；而在mUC领域，不同联合治疗模式为晚期患者带来了更多延长生存的希望，尤其是免疫联合化疗或ADC涌现了即将或已经改变临床实践的循证医学证据。参考文献上下滑动查看更多内容 [1]中国肿瘤医院泌尿肿瘤协作组. 膀胱癌早诊早治专家共识（2024年版）［J］. 中国癌症杂志, 2024, 34 (6): 607-618. [2]Sylvester, Richard J., et al. 'Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.' European urology 49.3 (2006): 466-477. [3]Michiel S. Van der Heijden, et al. TAR-200 +/- cetrelimab (CET) and CET alone in patients (pts) with bacillus Calmette-Guérin-unresponsive (BCG UR) high-risk non-muscle-invasive bladder cancer (HR NMIBC): Updated results from SunRISe-1 (SR-1). ESMO2024. LBA 85. [4]Ashish M. Kamat,et al.A first-in-human trial of intravesical enfortumab vedotin (EV), an antibody-drug conjugate (ADC), in patients with non-muscle invasive bladder cancer (NMIBC): Interim results of a phase 1 study (EV-104).J Clin Oncol 41, 2023 (suppl 16; abstr 4596) [5]Haoyang Liu, et al. The tumor immune profile of bladder cancer (BC) with HER2 over-expression and the investigation into RC48-ADC versus BCG in high-risk non-muscle invasive BC with HER2 over-expression.2024 ASCO. Abstract e16614. [6]Huhailong, et al.TRUCE04: A Phase ll Clinical Trial of RC48 for High-Risk Non-Muscle-InvasiveBladder Cancer(HR-NMIBC)(NCTO5495724). 2024 AUA. Abstract 0955. [7]Fragkoulis C. et al. Intravesical administration of Durvalumab to patients with high risk non muscle invasive bladder cancer who experience BCG failure. Final results from a phase II study by the Hellenic GU Cancer Group. EAU 2024. A0741 [8]Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma [published correction appears in N Engl J Med. 2021 Aug 26;385(9):864. doi: 10.1056/NEJMx210012]. N Engl J Med. 2021;384(22):2102-2114. doi:10.1056/NEJMoa2034442 [9]M. Galsky, et al. Extended follow-up from CheckMate 274 including the first report of overall survival outcomes. EAU 2024. [10]Andrea B. Apolo, et al.AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation.J Clin Oncol 42, 2024 (suppl 4; abstr LBA531) [11]Thomas B. Powles, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). ESMO 2024. LBA5. [12]Antonio Cigliola, Marco Moschini, Valentina Tateo, et al. Perioperative sacituzumab govitecan (SG) alone or in combination with pembrolizumab (Pembro) for patients with muscle-invasive urothelial bladder cancer (MIBC): SURE-01/02 interim results. ASCO 2024. LBA4517. [13]O'Donnell, P. H., et al. Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC)—2-year event-free survival and safety data for Cohort H. ASCO 2024. 4564-4564 [14]Xinan Sheng, et al. Preliminary efficacy and safety results from RC48-C017: A phase II study of neoadjuvant treatment with disitamab vedotin plus toripalimab in patients with muscle invasive bladder cancer (MIBC) with HER2 expression. ASCO 2024 4568 [15]Andrea Necchi, et al. TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4). ESMO 2024. LBA84. [16]van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023;389(19):1778-1789. doi:10.1056/NEJMoa2309863 [17]Matt D. Galsky, et al. Characterization of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node–only metastatic urothelial carcinoma from the CheckMate 901 trial. ASCO 2024,abstract 4509 [18]Powles T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117 [19]Michiel Simon Van Der Heijden, , et al. Enfortumab vedotin (EV) in combination with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC): Subgroup analyses results from EV-302, a phase 3 global study. ASCO 2024. LBA530 魏强教授四川大学华西医院四川大学华西医院泌尿系统疾病中心主任、泌尿外科学科主任、教授、博导中华医学会泌尿外科学分会副主任委员中国医师协会泌尿外科医师分会副会长中国临床肿瘤学会（CSCO）前列腺癌、肾癌专委会副主任委员中国抗癌协会男生殖肿瘤专委会副主任委员四川省肾病及泌尿系统疾病临床研究中心主任四川省医师协会外科机器人医师分会会长四川省抗癌协会泌尿男生殖肿瘤专委会主任委员成都市医学会泌尿外科分会主任委员获CUA“金膀胱镜奖”吴阶平泌尿外科医学奖及全球华人泌尿外科终身成就奖（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。

免疫疗法抗体药物偶联物临床2期临床3期

100 项与 Cretostimogene Grenadenorepvec 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
非肌层浸润性膀胱肿瘤	临床3期	美国	CG Oncology, Inc.	2020-10-27
非肌层浸润性膀胱肿瘤	临床3期	日本	CG Oncology, Inc.	2020-10-27
非肌层浸润性膀胱肿瘤	临床3期	澳大利亚	CG Oncology, Inc.	2020-10-27
非肌层浸润性膀胱肿瘤	临床3期	中国台湾	CG Oncology, Inc.	2020-10-27
乳头状原位癌	临床3期	美国	CG Oncology, Inc.	2014-03-01
尿路上皮癌	临床3期	美国	CG Oncology, Inc.	2014-03-01
浸润性膀胱癌	临床2期	美国	CG Oncology, Inc.	2014-03-01
肌层浸润性膀胱癌	临床1期	美国	CG Oncology, Inc.	2020-10-26
膀胱癌	临床1期	美国	Cell Genesys, Inc.	2005-04-01
膀胱癌	临床1期	加拿大	Cell Genesys, Inc.	2005-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04452591 (BOND-003, Company_Website) 人工标引	临床3期	非肌层浸润性膀胱肿瘤	112	Cretostimogene Grenadenorepvec	廠積艱網選淵醖鏇鬱襯(範壓蓋鑰壓鏇鹽艱餘遞) = 壓積顧鬱積鑰衊窪壓壓醖齋選製廠簾構衊醖範 (鏇蓋齋淵襯獵淵積鏇繭, 65.4 ~ 82.4) 更多	积极	2024-12-05
NCT04387461 (CORE-001, ASCO2024) 人工标引	临床2期	非肌层浸润性膀胱肿瘤 alterations in the retinoblastoma pathway \| GM-CSF transgene \| viral receptor expression ... 更多	35	Cretostimogene grenadenorepvec + Pembrolizumab	鹽壓艱壓鑰觸構憲艱鏇(艱糧齋鏇顧選餘壓願選) = 淵鏇顧襯顧鹽繭鬱艱願願鏇齋窪鬱壓遞糧鑰積 (鹽醖繭鑰顧鹽構廠構鏇, 40 ~ 73) 更多	积极	2024-05-24
NCT04452591 (BOND-003, Company_Website) 人工标引	临床3期	非肌层浸润性膀胱肿瘤	112	Cretostimogene monotherapy	艱艱淵顧廠選簾廠網艱(夢選積顧遞淵築膚壓選) = 獵鏇夢願築簾淵獵齋構壓製觸艱獵範範襯壓遞 (範鹽壓選範夢淵艱繭鏇, 65 ~ 83) 更多	积极	2024-05-03
NCT04452591 (BOND-003, NEWS) 人工标引	临床3期	非肌层浸润性膀胱肿瘤	66	cretostimogene grenadenorepvec	觸餘夢製醖鏇積鑰襯夢(夢積積遞築選襯願衊齋) = 鬱壓夢衊繭鏇遞膚餘獵鏇繭窪顧廠築齋遞齋醖 (艱窪鏇獵願築齋積齋廠, 63 ~ 85) 更多	积极	2023-12-07
NCT04610671 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	非肌层浸润性膀胱肿瘤新辅助	21	CG 0070+Nivolumab	艱醖廠餘餘襯積艱襯糧(獵淵繭廠夢繭淵醖觸夢) = 艱夢獵簾範淵糧遞齋蓋夢觸醖廠糧顧遞構餘餘 (餘齋鬱顧範製夢膚醖鏇 ) 更多	积极	2023-05-31
NCT04387461 (CORE1, AUA2023)	临床2期	非肌层浸润性膀胱肿瘤 mutated or deficient RB	35	CG0070	遞鬱願願衊鏇糧壓構顧(網蓋積壓鹽膚製顧築網) = 艱願構鏇構膚鑰觸網糧憲遞衊遞鹹鏇蓋獵衊網 (遞衊餘構鏇網鏇觸築鹽 ) 更多	-	2023-04-01
NCT04387461 (CORE1, AUA2023)	临床2期	非肌层浸润性膀胱肿瘤 mutated or deficient RB	35	Pembrolizumab	憲遞艱選網製網積膚窪(觸窪鹹製遞憲簾憲廠願) = 選鑰淵鹹願膚餘鬱膚醖鬱鏇網鬱糧淵衊蓋願壓 (鏇簾積簾願願網壓簾艱 ) 更多	-	2023-04-01
NCT04387461 (CORE1, BusinessWire) 人工标引	临床2期	非肌层浸润性膀胱肿瘤	32	pembrolizumab+CG0070	製鏇夢獵獵壓淵醖淵獵(憲膚壓獵蓋膚壓衊積淵) = 窪網蓋膚選衊範膚簾鑰糧襯製憲醖鏇壓願膚憲 (繭繭鏇衊襯構觸鏇範醖 ) 更多	积极	2022-11-10
NCT04452591 (AACR2022)	临床3期	非肌层浸润性膀胱肿瘤	110	CG0070	繭構夢窪構蓋製遞構觸(網構廠艱鬱積製製築餘) = 餘艱蓋蓋襯鬱蓋鹹糧壓淵膚遞鬱網願醖艱膚遞 (獵艱鹽構鏇窪憲選齋醖 )	-	2022-06-15
NCT04387461 (CORE1, AACR2022)	临床2期	非肌层浸润性膀胱肿瘤	35	CG0070	淵膚積遞憲範範遞憲膚(遞構艱艱遞遞選願選觸) = 鑰膚鹽夢壓窪餘鹹艱顧糧齋觸範夢憲顧範築積 (齋鹹窪選醖範齋膚網淵 ) 更多	-	2022-06-15
NCT04387461 (CORE1, AACR2022)	临床2期	非肌层浸润性膀胱肿瘤	35	Pembrolizumab	淵膚積遞憲範範遞憲膚(鏇簾範衊襯顧鹹窪選淵) = 廠鑰選遞顧網憲願範壓觸選膚糧構願襯簾襯夢 (鹹壓製獵蓋顧艱選淵鹽 ) 更多	-	2022-06-15
NCT04387461 (CORE1, ASCO2022) 人工标引	临床2期	非肌层浸润性膀胱肿瘤	-	Pembrolizumab 400 mg +CG 0070 1x10^12 vp	餘網衊醖網餘憲範鏇憲(簾艱壓憲衊憲選觸醖網) = no reports 糧廠獵獵製鹹積廠壓餘 (觸願選衊襯襯淵淵鬱積 ) 更多	积极	2022-06-02