Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: Results of a first-in-human Phase 1 trial

Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: Results of a first-in-human Phase 1 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 Article Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: Results of a first-in-human Phase 1 trial Jong Chul PARK, Brendan Curti, Marcus Butler, Joseph Elassal, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5984691/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Anchored immunotherapy is a novel approach for retaining high doses of drugs within the tumor microenvironment improving the therapeutic window . Tolododekin alfa is a first-in-class anchored drug conjugate in which IL-12 is linked to aluminum hydroxide. Safety and biologic activity was evaluated in a Phase 1 clinical trial in patients with accessible advanced solid tumors. The primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics, preliminary antitumor activity, and immunogenicity. Fifteen patients were enrolled and dosed at escalating doses of tolododekin alfa given by direct injection once every 3 weeks. There were no dose-limiting toxicities or treatment-related serious adverse events. PK/PD measurements demonstrated retention of drug in the tumor at all dose levels. Biologic activity was demonstrated by increased CD8+ T cells, PD-L1 expression, and prolonged pro-inflammatory gene expression. Nine patients (60%) achieved disease control. These findings support continued clinical development of tolododekin alfa. ClinicalTrials.gov registration: NCT06171750. Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy Biological sciences/Cancer/Tumour immunology Anchored immunotherapy Cancer Interleukin-12 Phase 1 Treatment Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Nature Communications → 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-5984691","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":415884366,"identity":"18360377-59af-4b86-bd60-3eca8e313e56","order_by":0,"name":"Jong Chul 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