{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:22:05Z","timestamp":1780978925660,"version":"3.54.1"},"reference-count":37,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2) could be a promising strategy for HER2-expressing gastric cancer or gastroesophageal junction adenocarcinoma (GC\/GEJ) and colorectal cancer (CRC). We conducted a phase I trial to assess trastuzumab rezetecan, a novel HER2-targeted ADC, in HER2-expressing advanced GC\/GEJ and CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients with HER2-expressing advanced GC\/GEJ and CRC whose disease progressed on and\/or had no available\/applicable standard treatment were enrolled. Patients were intravenously given trastuzumab rezetecan at 3.2, 4.8, 6.4, and 8.0 mg\/kg (once every 3 weeks) in an i3+3 dose-escalation scheme, followed by pharmacokinetics expansion at selected doses and then clinical expansion. The primary end points were dose-limiting toxicity (DLT) and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Between March 30, 2021, and August 1, 2023, 100 patients were enrolled (57 with GC\/GEJ and 43 with CRC). One DLT occurred in the 8.0 mg\/kg dose cohort. Grade \u22653 treatment-related adverse events (TRAEs) were reported in 66 (66.0%) patients. Only 5 (5.0%) patients discontinued treatment because of TRAEs. In HER2-positive GC\/GEJ (n = 40), trastuzumab rezetecan achieved an objective response rate (ORR) of 45.0%, a median progression-free survival (PFS) of 9.0 months (95% CI, 7.0 to 11.3), and a median overall survival (OS) of 16.3 months (95% CI, 12.4 to not reached [NR]). In GC\/GEJ with HER2 immunohistochemical 2+ and in situ hybridization\u2013negative (n = 12), trastuzumab rezetecan had an ORR of 25.0%, a median PFS of 12.2 months (95% CI, 2.8 to 14.0), and an immature median OS. In HER2-positive CRC (n = 37), trastuzumab rezetecan had an ORR of 40.5%, a median PFS of 9.5 months (95% CI, 7.3 to 11.2), and a median OS of 22.7 months (95% CI, 17.5 to NR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Trastuzumab rezetecan showed tolerable safety and preliminary efficacy in HER2-expressing advanced GC\/GEJ and CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00716","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:59:31Z","timestamp":1772657971000},"page":"1225-1237","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Trastuzumab Rezetecan in Human Epidermal Growth Factor Receptor 2\u2013Expressing Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer: A Multicenter, Open-Label, Phase I Trial"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct04513223","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tianshu","family":"Liu","sequence":"first","affiliation":[{"name":"Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Luo","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center, The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Digestive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of GCP, Shanxi Province Cancer Hospital\/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences\/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-8026","authenticated-orcid":true,"given":"Yanhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Oncology Internal Medicine First District, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Oncology Department, The First Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulin","family":"Liu","sequence":"additional","affiliation":[{"name":"Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Lab, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-2049","authenticated-orcid":true,"given":"Xiubao","family":"Ren","sequence":"additional","affiliation":[{"name":"Biotherapy Department, Tianjin Medical University Cancer Institute &amp; 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