{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:57:20Z","timestamp":1788195440876,"version":"build-2803163510"},"reference-count":27,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Incubation Fund of Renji Hospital","award":["RJTJ22-MS-025(Xiang Xia)"],"award-info":[{"award-number":["RJTJ22-MS-025(Xiang Xia)"]}]},{"name":"State Key Laboratory of Systems Medicine for Cancer","award":["KF2205-93(Zizhen Zhang)"],"award-info":[{"award-number":["KF2205-93(Zizhen Zhang)"]}]},{"name":"Shanghai \"Rising Stars\u201d Young Medical Talent Training Subsidy Program","award":["2022-65(Xiang Xia)"],"award-info":[{"award-number":["2022-65(Xiang Xia)"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103510(Zizhen,Zhang)"],"award-info":[{"award-number":["82103510(Zizhen,Zhang)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303428(Bo Ni)"],"award-info":[{"award-number":["82303428(Bo Ni)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473065(Xiang Xia)"],"award-info":[{"award-number":["82473065(Xiang Xia)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473077(Zizhen,Zhang)"],"award-info":[{"award-number":["82473077(Zizhen,Zhang)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,5,12]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immunotherapy has revolutionised cancer treatment. Immune checkpoint inhibitors have demonstrated significant efficacy across multiple tumour types, including gastric cancer, where several approved programmed cell death 1\/programmed\u2009cell death-ligand 1 (PD-1\/PD-L1) inhibitors show promising antitumour activity. While PD-L1 expression serves as a predictive biomarker for PD-1 inhibitor response, and PD-L1-positive patients generally show better outcomes, therapeutic resistance remains a challenge. Many initial responders eventually develop resistance, and surprisingly, some PD-L1-positive patients fail to achieve expected response rates, indicating emerging resistance mechanisms in potentially responsive populations. Adebrelimab, a PD-L1 inhibitor, demonstrates mechanistic advantages over PD-1 inhibitors, with clinical studies suggesting promising therapeutic potential. When combined with irinotecan, apatinib has shown efficacy in second-line gastric cancer treatment. This study aims to evaluate the efficacy and safety of combining adebrelimab with apatinib and irinotecan for advanced gastric cancer refractory to PD-1 inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method and analysis<\/jats:title>\n                    <jats:p>This single-arm, single-centre exploratory trial will be conducted at Renji Hospital, enrolling 32 patients aged 18\u201375 years. Eligible patients must have initially achieved partial response, complete response or stable disease with progression-free survival (PFS)\u22653 months during prior immunotherapy but subsequently progressive disease on imaging. Treatment will continue until meeting discontinuation criteria. The primary endpoint is objective response rate with Clopper-Pearson 95% CI. Secondary endpoints include disease control rate (95%\u2009CI), PFS and overall survival (estimated by Kaplan-Meier method), along with safety assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>All participants will provide informed consent. The protocol has been approved by the Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (LY2023-201-C). The results will be disseminated through peer-reviewed manuscripts, reports and presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2300077329.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-089286","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T15:25:25Z","timestamp":1749050725000},"page":"e089286","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical study of adebrelimab in combination with apatinib and irinotecan for PD-1 inhibitor-ineffective advanced-stage gastric cancer: study protocol for a single-arm, single-centre, exploratory trial"],"prefix":"10.1136","volume":"15","author":[{"given":"Tao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Shanghai Jiao 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