Novel Oncolytic Virus VG161 in Hepatocellular Carcinoma Patients Refractory to Standard Systemic Therapies

Novel Oncolytic Virus VG161 in Hepatocellular Carcinoma Patients Refractory to Standard Systemic Therapies | 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 Biological Sciences - Article Novel Oncolytic Virus VG161 in Hepatocellular Carcinoma Patients Refractory to Standard Systemic Therapies Tingbo Liang, Yinan Shen, Xueli Bai, Qi Zhang, Xingmei Liang, and 35 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4608261/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Mar, 2025 Read the published version in Nature → Version 1 posted You are reading this latest preprint version Abstract For hepatocellular carcinoma (HCC) patients, treatment options are limited after failing second-line therapy. This phase I, multicenter trial evaluates the safety and antitumor efficacy of VG161 in patients with advanced liver cancer. The study included dose escalation using a ‘3 + 3’ design across five dose levels, followed by a dose expansion phase using Simon’s two-stage design. Forty-four patients received doses with no dose-limiting toxicity observed. Among the 40 HCC patients, 37 were evaluable. The objective response rate (ORR) was 18.92%, and the disease control rate (DCR) was 64.86%. The median progression-free survival (PFS) was 2.9 months, and overall survival (OS) was 12.4 months. Subgroup analysis showed that among 34 patients who had failed second-line treatment, the ORR was 17.65% and the DCR was 64.71%. The median PFS and OS for this group were 2.8 and 9.4 months, respectively. Patients with prior checkpoint inhibitor treatment (PreCPI) longer than 3 months had a median OS of 17.3 months, compared to 7.4 months for those with PreCPI ≤ 3 m (p = 0.04). Additionally, patients receiving systemic therapies after VG161 showed longer survival (p = 0.03). Multiple detection techniques revealed that VG161 reshapes the immune microenvironment of HCC, enhancing tumor sensitivity to systemic treatments. An efficacy prediction model based on differentially expressed genes was established, which successfully predicts prolonged OS in study patients (p < 0.001) but not in public database patients (p = 0.17). Anti-hepatitis B agents were confirmed to not affect the replication and efficacy of VG161. In summary, VG161 demonstrated comparable efficacy to second-line treatments in third-line patients, providing a new option for patients who have failed second-line therapy. It was well-tolerated and showed promising efficacy, extending survival in some subgroups and enhancing post-treatment systemic therapy efficacy, supporting its potential use in combination treatments. ClinicalTrials.gov registration: NCT04806464. Health sciences/Medical research/Drug development Health sciences/Diseases/Cancer/Gastrointestinal cancer/Liver cancer Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 19 Mar, 2025 Read the published version in Nature → Version 1 posted 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-4608261","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":318873520,"identity":"b0a8da72-5e61-49d6-b49a-756704951561","order_by":0,"name":"Tingbo 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Therapies","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4608261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4608261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"For hepatocellular carcinoma (HCC) patients, treatment options are limited after failing second-line therapy. This phase I, multicenter trial evaluates the safety and antitumor efficacy of VG161 in patients with advanced liver cancer. The study included dose escalation using a ‘3 + 3’ design across five dose levels, followed by a dose expansion phase using Simon’s two-stage design. Forty-four patients received doses with no dose-limiting toxicity observed. Among the 40 HCC patients, 37 were evaluable. The objective response rate (ORR) was 18.92%, and the disease control rate (DCR) was 64.86%. The median progression-free survival (PFS) was 2.9 months, and overall survival (OS) was 12.4 months. Subgroup analysis showed that among 34 patients who had failed second-line treatment, the ORR was 17.65% and the DCR was 64.71%. The median PFS and OS for this group were 2.8 and 9.4 months, respectively. Patients with prior checkpoint inhibitor treatment (PreCPI) longer than 3 months had a median OS of 17.3 months, compared to 7.4 months for those with PreCPI ≤ 3 m (p = 0.04). Additionally, patients receiving systemic therapies after VG161 showed longer survival (p = 0.03). Multiple detection techniques revealed that VG161 reshapes the immune microenvironment of HCC, enhancing tumor sensitivity to systemic treatments. An efficacy prediction model based on differentially expressed genes was established, which successfully predicts prolonged OS in study patients (p \u003c 0.001) but not in public database patients (p = 0.17). Anti-hepatitis B agents were confirmed to not affect the replication and efficacy of VG161. In summary, VG161 demonstrated comparable efficacy to second-line treatments in third-line patients, providing a new option for patients who have failed second-line therapy. It was well-tolerated and showed promising efficacy, extending survival in some subgroups and enhancing post-treatment systemic therapy efficacy, supporting its potential use in combination treatments. 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