{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:58:58Z","timestamp":1791316738793,"version":"4.3.1"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0519700"],"award-info":[{"award-number":["2024ZD0519700"]}]},{"DOI":"10.13039\/501100001809","name":"the National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82241232"],"award-info":[{"award-number":["82241232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82272789"],"award-info":[{"award-number":["82272789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Chinese National Natural Science Foundation project","award":["82073396"],"award-info":[{"award-number":["82073396"]}]},{"name":"the Chinese National Natural Science Foundation project","award":["82473346"],"award-info":[{"award-number":["82473346"]}]},{"name":"Guangzhou Key Research and Development Plan","award":["202206010141"],"award-info":[{"award-number":["202206010141"]}]},{"name":"the Cancer Immunotherapy Research Foundation of Chinese Society of Clinical Oncology (CSCO)\u2014Junshi","award":["Y-JS2019-046"],"award-info":[{"award-number":["Y-JS2019-046"]}]},{"name":"Cancer Innovative Research Program of Sun Yat-sen University Cancer Center","award":["CIRP-SYSUCC-0028"],"award-info":[{"award-number":["CIRP-SYSUCC-0028"]}]},{"name":"Guangzhou Science and Technology Bureau Basic and Applied Basic Research Project","award":["SL2022A04J01033"],"award-info":[{"award-number":["SL2022A04J01033"]}]},{"name":"Young Talents program of Sun Yat-sen University Cancer Center","award":["YTP-SYSUCC-0094"],"award-info":[{"award-number":["YTP-SYSUCC-0094"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Y101D is a novel bispecific antibody targeting PD-L1 and TGF-\u03b2. This multicenter phase I study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of Y101D in patients with metastatic or locally advanced solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients who failed standard therapies were enrolled. In the dose-escalation and -expansion phases, Y101D was administered intravenously every 2\u2009weeks (Q2W) at 1, 3, 10, 20, and 30\u2009mg\/kg. Primary objectives were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in escalation, safety, and objective response rate (ORR) in expansion. Secondary objectives included pharmacokinetics\/pharmacodynamics parameters, and immunogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 50 enrolled patients, the most common treatment-related adverse events (TRAEs) were aspartate aminotransferase elevation (20.0%), gingival bleeding (18.0%), alanine aminotransferase elevation (14.0%), rash (14.0%), and proteinuria (14.0%). Grade \u2265 3 TRAEs occurred in 10.0% of patients, with no grade 4\/5 TRAEs. Immune-related adverse events (irAEs) occurred in 22.0%, predominantly grades 1-2. No DLTs were observed, and MTD was not reached. One extensive-stage small cell lung cancer (ES-SCLC) patient (20\u2009mg\/kg Q2W) achieved a confirmed partial response (ORR: 2.1%, 95% CI, 0.1%-11.3%). Median progression-free survival and overall survival were 1.3\u2009months (95% CI, 0.9-1.3) and 10.5\u2009months (95% CI, 6.6-12.7), respectively. The pharmacokinetic characteristics of single and multiple doses of 20\u2009mg\/kg Q3W and 1200\u2009mg Q3W supported the administration schedule of once every 3\u2009weeks. PD-L1 target occupancy exceeded 95% at 2\u2009h post-dose across all cohorts and remained sustained pre-dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Y101D monotherapy exhibited a manageable safety profile and on-target pharmacodynamic activity, with limited antitumor activity as a single agent. Further evaluation in disease-focused cohorts and rational combination regimens is warranted, including in ES-SCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial number registration<\/jats:title>\n                    <jats:p>NCT05028556<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag133","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:45:17Z","timestamp":1778240717000},"source":"Crossref","is-referenced-by-count":3,"title":["Phase I study of Y101D, a bispecific antibody targeting PD-L1 and TGF-\u03b2 in patients with advanced solid tumors"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2545-9145","authenticated-orcid":false,"given":"Haishuang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou 510060,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou 510060,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou, Guangdong 510060,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou 510060,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou, Guangdong 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