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

IF 58.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nature Medicine Pub Date : 2024-11-09 DOI:10.1038/s41591-024-03324-9
Roger Li, Nancy Y. Villa, Xiaoqing Yu, Joseph O. Johnson, Gustavo Borjas, Jasreman Dhillon, Carlos M. Moran-Segura, Youngchul Kim, Natasha Francis, Denise Dorman, John J. Powers, Wade J. Sexton, Philippe E. Spiess, Michael A. Poch, Logan Zemp, Scott M. Gilbert, Jingsong Zhang, Julio M. Pow-Sang, Alexander R. A. Anderson, Tingyi Li, Xuefeng Wang, G. Daniel Grass, James M. Burke, Colin P. N. Dinney, Paulo C. Rodriguez, Rohit K. Jain, James J. Mulé, Jose R. Conejo-Garcia
{"title":"Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial","authors":"Roger Li, Nancy Y. Villa, Xiaoqing Yu, Joseph O. Johnson, Gustavo Borjas, Jasreman Dhillon, Carlos M. Moran-Segura, Youngchul Kim, Natasha Francis, Denise Dorman, John J. Powers, Wade J. Sexton, Philippe E. Spiess, Michael A. Poch, Logan Zemp, Scott M. Gilbert, Jingsong Zhang, Julio M. Pow-Sang, Alexander R. A. Anderson, Tingyi Li, Xuefeng Wang, G. Daniel Grass, James M. Burke, Colin P. N. Dinney, Paulo C. Rodriguez, Rohit K. Jain, James J. Mulé, Jose R. Conejo-Garcia","doi":"10.1038/s41591-024-03324-9","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41591-024-03324-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
使用 nivolumab 的溶瘤免疫疗法治疗肌肉浸润性膀胱癌:1b 期试验
对于不符合顺铂治疗条件的肌层浸润性膀胱癌患者来说,安全有效的新辅助治疗是一项亟待解决的问题。在此,我们启动了一项1b期研究,在不符合顺铂治疗条件的cT2-4aN0-1M0肌层浸润性膀胱癌患者中,采用膀胱内注射克雷莫司汀-格雷纳多雷韦克(编码粒细胞-巨噬细胞集落刺激因子的5型溶瘤血清型腺病毒)与全身用尼伐单抗联合治疗。该研究的首要目标是衡量安全性,次要目标是评估抗肿瘤疗效(以病理完全反应和1年无复发生存率来衡量)。入组并接受治疗的 21 名患者均未出现剂量限制性毒性。联合治疗的病理完全反应率为 42.1%,1 年无复发生存率为 70.4%。病理反应与基线游离 E2F 活性和肿瘤突变负荷有关,但与 PD-L1 状态无关。虽然膀胱内溶瘤免疫疗法广泛诱导了T细胞浸润,但三级淋巴结构的形成、增大和成熟与完全应答特别相关,支持了体液和细胞免疫应答协调的重要性。总之,这些结果凸显了这种联合疗法在提高不符合顺铂治疗条件的肌层浸润性膀胱癌患者疗效方面的潜力,值得作为新辅助治疗方案进行更多研究。ClinicalTrials.gov 标识符:NCT04610671:NCT04610671。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Nature Medicine
Nature Medicine 医学-生化与分子生物学
CiteScore
100.90
自引率
0.70%
发文量
525
审稿时长
1 months
期刊介绍: Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.
期刊最新文献
Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections H5N1 from an infected dairy worker sheds light on viral transmission TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial Moving toward response-adapted trials in oncology Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1