{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:52Z","timestamp":1791474712909,"version":"4.3.4"},"reference-count":19,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"abstract":"\n Importance<\/jats:title>\n Very high-risk non\u2013muscle-invasive bladder cancer (VHR NMIBC) includes extensive high-grade T1 (T1HG) disease, T1HG with carcinoma in situ, variant histology, lymphovascular invasion, or bacille Calmette-Gu\u00e9rin (BCG)\u2013unresponsive disease. Transurethrally unresectable disease warrants radical cystectomy, but patients ineligible for or declining cystectomy lack established nonsurgical therapy.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the efficacy and safety of disitamab vedotin (DV, an anti-\n ERBB2<\/jats:italic>\n [formerly\n HER2<\/jats:italic>\n ] antibody-drug conjugate) plus tislelizumab (an anti\u2013programmed cell death 1 protein immune checkpoint inhibitor) in transurethrally unresectable\n ERBB2<\/jats:italic>\n -positive VHR NMIBC.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This was an open-label, single-arm, phase 2, nonrandomized clinical trial with a Simon 2-stage design, conducted in an academic hospital from August 2022 to May 2024 with a median follow-up of 29.4 months. The analysis included adults with transurethrally unresectable\n ERBB2<\/jats:italic>\n -positive NMIBC who met the 2019 European Association of Urology VHR criteria and who were ineligible for or declined cystectomy.\n <\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Patients received an intravenous injection of DV (120 mg, day 1) plus tislelizumab (200 mg, day 2) every 3 weeks for 3 cycles; patients who responded received up to 8 DV cycles and 17 tislelizumab cycles.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was complete response (CR) of high-risk disease, defined as no high-grade tumor, T1 disease, carcinoma in situ, or progression. Secondary outcomes were response duration, progression-free survival, overall survival, and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Among 137 screened patients, 28 participants (median [IQR] age, 72 [67-74] years; 25 male [89%]) were included. Two preassessment withdrawals were counted as nonresponders in the all-treated analysis, which left 26 efficacy-evaluable patients. CR of high-risk disease was achieved in 19 of 26 (73.1%; 95% CI, 54.8%-91.3%), meeting the prespecified 70% alternative-rate goal. Among all 28, 19 responded (67.9%; 95% CI, 49.4%-86.3%), exceeding the 17-response exact binomial threshold. Both analyses met the primary criterion. Among responders, the 24-month sustained response was 83.5% (95% CI, 68.0%-100.0%), and no muscle invasive or metastatic progression occurred. Treatment-related adverse events occurred in 25 patients (89.3%), most commonly paresthesia (12 [42.9%]), alopecia (11 [39.3%]), and pruritus (10 [35.7%]); 4 (14.3%) had grade 3 to 4 events; 2 (7.1%) discontinued treatment; and none had grade 5 events.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Findings of this nonrandomized clinical trial suggest that DV plus tislelizumab may show a high CR rate and durable disease control in patients with transurethrally unresectable\n ERBB2<\/jats:italic>\n -positive VHR NMIBC, supporting randomized clinical trials.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05495724<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.3909","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:00:45Z","timestamp":1791471645000},"source":"Crossref","is-referenced-by-count":0,"title":["Disitamab Vedotin Plus Tislelizumab in Transurethrally Unresectable,\n ERBB2<\/i>\n -Positive, Non\u2013Muscle-Invasive Bladder Cancer"],"prefix":"10.1001","author":[{"given":"Yunkai","family":"Qie","sequence":"first","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaipeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Department of Urology Surgery, Shanxi Provincial People\u2019s Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwang","family":"Huang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Department of Urology, The Third Medical Center, Chinese People\u2019s Liberation Army General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology, Chu Hsien-I Memorial Hospital, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China"},{"name":"Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin 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