Nab-Paclitaxel, S-1, and Tislelizumab as First-Line Therapy in Advanced Gastric/GEJ Adenocarcinoma: a Phase II Single-Arm Trial

Nab-Paclitaxel, S-1, and Tislelizumab as First-Line Therapy in Advanced Gastric/GEJ Adenocarcinoma: a Phase II Single-Arm Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Nab-Paclitaxel, S-1, and Tislelizumab as First-Line Therapy in Advanced Gastric/GEJ Adenocarcinoma: a Phase II Single-Arm Trial Yuejun Han, Qiyue Wang, Yinqi Chen, Hui Wu, Tongshuo Wu, Dongdong Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7828548/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Mar, 2026 Read the published version in BMC Cancer → Version 1 posted 19 You are reading this latest preprint version Abstract Background Platinum-based chemoimmunotherapy is the standard first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma but is often limited by cumulative toxicity, particularly in older patients and those with stroma-rich metastases. Methods We conducted an investigator-initiated, single-arm, single-center, phase II trial at the First Affiliated Hospital of Zhejiang University. Adults (18–85 years) with previously untreated, histologically confirmed advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Treatment comprised 21-day cycles of intravenous tislelizumab (200 mg, day 1), nab-paclitaxel (100 mg/m², days 1 and 8), and S-1 (an oral fluoropyrimidine) (80–120 mg orally twice daily, days 1–14). Surgical resectability was reassessed after 6–8 cycles by a multidisciplinary team; otherwise therapy continued until radiographic progression or unacceptable toxicity. Tumor response was assessed at baseline and every 2–4 cycles; adverse events were graded per NCI-CTCAE v5.0. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary endpoints included conversion surgery rate, overall survival (OS), disease control rate (DCR), and safety. ORR/DCR were summarized with exact (Clopper-Pearson) 95% CIs; PFS/OS were estimated by Kaplan-Meier with Greenwood standard errors and Brookmeyer-Crowley medians; landmark survival at 6, 12, and 18 months was reported. Results Among 43 enrolled patients, the confirmed ORR was 81.4% (95% CI: 66.6–91.6%) and the DCR was 90.7% (95% CI: 77.9–97.4%). The median PFS was 7.5 months (95% CI: 6.3–11.3), and the median OS was 20.1 months (95% CI: 14.2–22.0). Nine patients (20.9%) underwent conversion surgery, with two achieving pathological complete response. There were significant differences in terms of OS (median 29.5 vs 16.5 months, P = 0.042) in patients with conversion surgery than without. Patients showed significantly prolonged PFS (median 11.8 vs 7.2 months, P = 0.040) and OS (median 29.2 vs 16.4 months, P = 0.020) with age ≥ 65 than age ˂ 65. Grade ≥ 3 treatment-related adverse events included neutropenia (9.3%), leukopenia (7.0%), and anemia (2.3%). Conclusions The platinum-free triplet regimen of nab-paclitaxel, S-1, and tislelizumab demonstrated promising efficacy, including high response rates, encouraging survival outcomes, and a substantial conversion surgery rate, with a manageable safety profile. These findings warrant further validation in randomized controlled trials, and suggest this regimen as a potential therapeutic strategy, especially for older patients who may be less tolerant of platinum-based therapies. Trial registration: This study is registered with chictr.org.cn, ChiCTR2200062653; registered on 14 August 2022. Advanced gastric cancer Platinum-free chemotherapy Tislelizumab Albumin-bound paclitaxel Immunotherapy combination therapy Full Text Additional Declarations No competing interests reported. Supplementary Files TableS1.docx Doc.S1Detailedeligibilitycriteria.docx SupplementaryFigures.docx Cite Share Download PDF Status: Published Journal Publication published 17 Mar, 2026 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 02 Jan, 2026 Reviews received at journal 01 Jan, 2026 Reviews received at journal 28 Dec, 2025 Reviewers agreed at journal 28 Dec, 2025 Reviewers agreed at journal 26 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviewers agreed at journal 15 Dec, 2025 Reviewers agreed at journal 14 Dec, 2025 Reviewers agreed at journal 14 Dec, 2025 Reviewers agreed at journal 13 Dec, 2025 Reviews received at journal 12 Dec, 2025 Reviewers agreed at journal 30 Nov, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviewers invited by journal 05 Nov, 2025 Editor assigned by journal 04 Nov, 2025 Editor invited by journal 18 Oct, 2025 Submission checks completed at journal 17 Oct, 2025 First submitted to journal 17 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7828548","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":542977493,"identity":"644aaee1-0dc4-4372-b013-d48eadd1636a","order_by":0,"name":"Yuejun Han","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuejun","middleName":"","lastName":"Han","suffix":""},{"id":542977494,"identity":"5d72ed19-9280-43e3-8099-01b62ba0404d","order_by":1,"name":"Qiyue Wang","email":"","orcid":"","institution":"Zhejiang University School of 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Trial","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Advanced gastric cancer, Platinum-free chemotherapy, Tislelizumab, Albumin-bound paclitaxel, Immunotherapy combination therapy","lastPublishedDoi":"10.21203/rs.3.rs-7828548/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7828548/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePlatinum-based chemoimmunotherapy is the standard first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma but is often limited by cumulative toxicity, particularly in older patients and those with stroma-rich metastases.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe conducted an investigator-initiated, single-arm, single-center, phase II trial at the First Affiliated Hospital of Zhejiang University. Adults (18\u0026ndash;85 years) with previously untreated, histologically confirmed advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Treatment comprised 21-day cycles of intravenous tislelizumab (200 mg, day 1), nab-paclitaxel (100 mg/m\u0026sup2;, days 1 and 8), and S-1 (an oral fluoropyrimidine) (80\u0026ndash;120 mg orally twice daily, days 1\u0026ndash;14). Surgical resectability was reassessed after 6\u0026ndash;8 cycles by a multidisciplinary team; otherwise therapy continued until radiographic progression or unacceptable toxicity. Tumor response was assessed at baseline and every 2\u0026ndash;4 cycles; adverse events were graded per NCI-CTCAE v5.0. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary endpoints included conversion surgery rate, overall survival (OS), disease control rate (DCR), and safety. ORR/DCR were summarized with exact (Clopper-Pearson) 95% CIs; PFS/OS were estimated by Kaplan-Meier with Greenwood standard errors and Brookmeyer-Crowley medians; landmark survival at 6, 12, and 18 months was reported.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 43 enrolled patients, the confirmed ORR was 81.4% (95% CI: 66.6\u0026ndash;91.6%) and the DCR was 90.7% (95% CI: 77.9\u0026ndash;97.4%). The median PFS was 7.5 months (95% CI: 6.3\u0026ndash;11.3), and the median OS was 20.1 months (95% CI: 14.2\u0026ndash;22.0). Nine patients (20.9%) underwent conversion surgery, with two achieving pathological complete response. There were significant differences in terms of OS (median 29.5 vs 16.5 months, P\u0026thinsp;=\u0026thinsp;0.042) in patients with conversion surgery than without. Patients showed significantly prolonged PFS (median 11.8 vs 7.2 months, P\u0026thinsp;=\u0026thinsp;0.040) and OS (median 29.2 vs 16.4 months, P\u0026thinsp;=\u0026thinsp;0.020) with age\u0026thinsp;\u0026ge;\u0026thinsp;65 than age ˂ 65. Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 treatment-related adverse events included neutropenia (9.3%), leukopenia (7.0%), and anemia (2.3%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe platinum-free triplet regimen of nab-paclitaxel, S-1, and tislelizumab demonstrated promising efficacy, including high response rates, encouraging survival outcomes, and a substantial conversion surgery rate, with a manageable safety profile. These findings warrant further validation in randomized controlled trials, and suggest this regimen as a potential therapeutic strategy, especially for older patients who may be less tolerant of platinum-based therapies.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eThis study is registered with chictr.org.cn, ChiCTR2200062653; registered on 14 August 2022.\u003c/p\u003e","manuscriptTitle":"Nab-Paclitaxel, S-1, and Tislelizumab as First-Line Therapy in Advanced Gastric/GEJ Adenocarcinoma: a Phase II Single-Arm Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 20:20:33","doi":"10.21203/rs.3.rs-7828548/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-02T14:51:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-01T09:30:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-28T13:19:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236851073830739801589930363268739004867","date":"2025-12-28T08:24:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"301211438933122810991429374263642373780","date":"2025-12-26T16:55:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215156822142605047313276210146362555545","date":"2025-12-18T10:53:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296857307633777543579150263282223958337","date":"2025-12-15T09:10:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286868353345378495864838347706876142809","date":"2025-12-14T21:40:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161280912443249511215516896261251262090","date":"2025-12-14T05:41:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109917319434183013823521287454943388382","date":"2025-12-13T11:50:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-12T20:41:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179340904335494908507890083593086925475","date":"2025-11-30T18:54:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"257784894705308769533502487927684484411","date":"2025-11-25T20:00:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174604087378005343793825437837966865607","date":"2025-11-25T19:14:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-05T07:31:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-04T08:34:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-18T17:49:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-17T11:03:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-10-17T10:58:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"21334b55-26e7-4598-865f-0757eb0f4119","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:02:45+00:00","versionOfRecord":{"articleIdentity":"rs-7828548","link":"https://doi.org/10.1186/s12885-026-15849-y","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2026-03-17 15:59:23","publishedOnDateReadable":"March 17th, 2026"},"versionCreatedAt":"2025-11-14 20:20:33","video":"","vorDoi":"10.1186/s12885-026-15849-y","vorDoiUrl":"https://doi.org/10.1186/s12885-026-15849-y","workflowStages":[]},"version":"v1","identity":"rs-7828548","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7828548","identity":"rs-7828548","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}