{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:11:40Z","timestamp":1792876300947,"version":"4.5.0"},"reference-count":37,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC). However, many patients are ineligible for or refuse cisplatin. SunRISe-4 (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04919512\">NCT04919512<\/jats:ext-link>\n                      ) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200\/gem-iDRS) plus cetrelimab or cetrelimab monotherapy in patients with MIBC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Adults with Eastern Cooperative Oncology Group performance status 0-1, cT2-T4a N0M0, ineligible\/refusing NAC, and planned for RC were randomly assigned 5:3, stratified by transurethral resection of bladder tumor completeness (residual tumor \u22643 cm permitted) and T stage, to receive TAR-200 plus cetrelimab (cohort 1) or cetrelimab monotherapy (cohort 2). The primary end point was pathologic complete response (pCR) at RC. Secondary end points included recurrence-free survival (RFS) and safety. Exploratory end points included pathologic overall response (pOR; \u2264ypT1N0) and circulating tumor (ct) and urinary tumor (ut) DNA molecular residual disease (MRD). Side-by-side descriptive efficacy summary was planned.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At the May 9, 2025, data cutoff, 159 patients were treated; 88 in cohort 1 and 46 in cohort 2 underwent RC. pCR, pOR, and 1-year RFS rates were 38%, 53%, and 77% in cohort 1 and 28%, 44%, and 64% in cohort 2, respectively. pCR rates were consistent across subgroups. No new safety signals were observed. Across cohorts, utDNA\u2013 status before RC (week 12) and utDNA clearance correlated with pCR (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 10\n                      <jats:sup>\u20135<\/jats:sup>\n                      and &lt; 10\n                      <jats:sup>\u20133<\/jats:sup>\n                      , respectively). ctDNA\u2013 status at baseline and week 12 was associated with longer RFS compared with ctDNA+ status at the same time point (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .04 and 0.01, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rates compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. utDNA and ctDNA MRD results support further investigation as biomarkers for residual local and nonlocal disease, respectively.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02382","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T21:00:14Z","timestamp":1764795614000},"page":"586-597","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Gemcitabine Intravesical System Plus Cetrelimab or Cetrelimab Alone as Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: SunRISe-4 Primary Analysis and Biomarker Results"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-2756","authenticated-orcid":false,"given":"Andrea","family":"Necchi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-3465","authenticated-orcid":false,"given":"F\u00e9lix","family":"Guerrero-Ramos","sequence":"additional","affiliation":[{"name":"Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Crispen","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Herrera-Imbroda","sequence":"additional","affiliation":[{"name":"Urology Department, Hospital Universitario Virgen de la Victoria, IBIMA-Plataforma BIONAND, M\u00e1laga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-5602","authenticated-orcid":false,"given":"Rohan","family":"Garje","sequence":"additional","affiliation":[{"name":"Miami Cancer Institute, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-0032","authenticated-orcid":false,"given":"Bernadett","family":"Szabados","sequence":"additional","affiliation":[{"name":"Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom"},{"name":"Department of Urology, University College London Hospital NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8778-9759","authenticated-orcid":false,"given":"Charles C.","family":"Peyton","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Alabama at Birmingham, Birmingham, 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