{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:35:23Z","timestamp":1790354123353,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571077"],"award-info":[{"award-number":["32571077"]}],"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":["82403927"],"award-info":[{"award-number":["82403927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH164"],"award-info":[{"award-number":["ZR2022MH164"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Perioperative treatment of gastric and gastroesophageal junction (G\/GEJ) cancer is evolving towards multimodal strategies incorporating HER2\u2010targeted therapy, immunotherapy and chemotherapy. Disitamab vedotin (RC48), an HER2\u2010targeted antibody\u2013drug conjugate, shows promising antitumour activity and potential synergy with immune checkpoint inhibitors. This study evaluated neoadjuvant RC48 combined with camrelizumab and S\u20101 in resectable HER2\u2010overexpressing locally advanced G\/GEJ adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with histologically confirmed HER2\u2010overexpressing (IHC 3+ or 2+) resectable G\/GEJ cancer staged as cT3\u20104aN1\u20103M0 were enrolled in this prospective single\u2010arm phase II study. Patients received three 3\u2010weekly cycles of RC48, camrelizumab and S\u20101 before surgery. Pathological complete response (pCR) was defined as the primary endpoint, whereas major pathological response (MPR), objective response rate (ORR), tumour downstaging, disease\u2010free survival (DFS), overall survival (OS) and safety were evaluated as secondary endpoints. Exploratory circulating tumour DNA (ctDNA) methylation profiling (PredicineEPIC) assessed molecular response dynamics and ERBB2 copy number variation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 18 September 2022 to 12 December 2024, 32 patients were enrolled; 24 proceeded to D2 resection. The ORR after neoadjuvant therapy was 80.0% (24\/30). In the surgical cohort, pCR and MPR were achieved in 25.0% (6\/24) and 45.8% (11\/24) of patients, respectively, with an R0 resection rate of 100%. The median DFS and OS were not reached at the time of analysis. In the ctDNA substudy (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014), methylation\u2010derived tumour fraction declined during therapy and ERBB2 plasma copy number gain aligned with tissue HER2 status. Treatment\u2010related adverse events of grade \u22653 were reported in 31.3% of patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neoadjuvant RC48 combined with camrelizumab and S\u20101 showed potential antitumour activity with an acceptable safety profile in HER2\u2010overexpressing locally advanced resectable G\/GEJ adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Neoadjuvant RC48 plus camrelizumab and S\u20101 showed encouraging pathological responses in HER2\u2010overexpressing gastric cancer.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The regimen achieved a pCR rate of 25% and an MPR rate of 45.8%.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The combination therapy demonstrated a manageable safety profile.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exploratory ctDNA methylation analysis suggested potential for dynamic response monitoring.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70679","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T07:42:45Z","timestamp":1778053365000},"source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S\u20101 for neoadjuvant therapy of locally advanced gastric cancer with HER2\u2010overexpressing: Preliminary results of a prospective, single\u2010arm, phase II study"],"prefix":"10.1002","volume":"16","author":[{"given":"Longgang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Gastric Surgery Ward Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan 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