{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:20:13Z","timestamp":1793996413367,"version":"4.8.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This multicenter, open-label, phase Ib\/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with histologically confirmed aHCC were included to receive either 6 mg\/kg cadonilimab every 2 weeks plus lenvatinib (cohort A) or 15 mg\/kg cadonilimab every 3 weeks plus lenvatinib (cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, while the secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 59 patients were enrolled (31 in cohort A and 28 in cohort B). The median follow-up time was 27.4 months as of the data cutoff date (July 28, 2023). The ORR in cohort A was 35.5% (95% CI: 19.2, 54.6) and that in cohort B was 35.7% (95% CI: 18.6, 55.9), and the median DoR was 13.6 months (95% CI: 4.14, NE) and 13.67 months (95% CI: 3.52, NE), respectively. The median PFS was 8.6 months (95% CI: 5.2, 15.2) and 9.8 months (95% CI: 6.9, 15.2), respectively. The median OS was 27.1 months (95% C: 15.7, NE) for cohort A, while it was not reached for cohort B. Grade \u2265 3 treatment-related adverse events (TRAEs) were reported in 66.1% of patients, with serious TRAEs occurring in 39.0% of cases. Decreased platelet count (47.5%), proteinuria (45.8%), hypertension (44.1%), and white blood cell count (44.1%) were the most common TRAEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This novel combination therapy showed promising efficacy and manageable toxicity that could provide an option in first-line setting of aHCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>[<jats:uri>www.ClinicalTrials.gov<\/jats:uri>], NCT04444167.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1238667","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T13:09:00Z","timestamp":1698152940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib\/II single-arm clinical 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