{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:56:03Z","timestamp":1790301363910,"version":"4.1.0"},"reference-count":45,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"unspecified","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8257100924"],"award-info":[{"award-number":["8257100924"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,6,22]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Patients with very-high risk clear cell renal cell carcinoma (ccRCC) remain at substantial risk of recurrence after nephrectomy. However, heterogeneity in benefit from adjuvant immunotherapy observed in the KEYNOTE-564 trial, together with limited prospective data in this population, warrants further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, prospective, non-randomized, controlled phase II trial enrolled patients with very-high risk ccRCC following nephrectomy. Patients received either adjuvant penpulimab or routine surveillance, with 1:1 propensity score matching (PSM) applied to balance baseline characteristics. The primary endpoint was disease-free survival (DFS), with secondary endpoints including overall survival (OS) and safety. Plasma proteomic and metabolomic profiling was conducted for exploratory analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Given the non-randomized design, baseline imbalances were addressed by PSM, yielding well-balanced cohorts of 87 patients per group. Adjuvant penpulimab was associated with improved DFS compared with surveillance (HR, 0.37; 95%\u2009CI 0.16 to 0.89; p=0.026), whereas OS data remained immature. Consistent with Kaplan-Meier estimates, 1-year (94.25% vs 80.46%) and 2-year (88.68% vs 75.38%) DFS rates favored the penpulimab group (log-rank p=0.026). Penpulimab was generally well tolerated, with most treatment-related adverse events being grade 1\u20132. Plasma proteomic and metabolomic analyses revealed enrichment of immune response-related pathways in patients without disease progression, with circulating biomarkers associated with DFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adjuvant penpulimab was associated with improved DFS and a manageable safety profile in patients with very-high risk ccRCC. Plasma-based biomarkers associated with disease progression may inform postoperative risk stratification and warrant further validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2200062189.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015686","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:20:38Z","timestamp":1783682438000},"page":"e015686","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Adjuvant penpulimab in very-high risk clear cell renal cell carcinoma: a prospective, non-randomized, controlled phase II trial with integrated plasma multi-omics 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