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SGN-B6A is an antibody–drug conjugate delivering the MMAE payload selectively to integrin beta-6–expressing cancer cells, without binding other alpha-v family members. Preclinical models show in vivo activity across multiple carcinoma types. In cynomolgus monkey toxicology, weekly dosing up to 5 mg/kg for four doses or 6 mg/kg every 3 weeks for two doses was tolerated, with MMAE-like hematologic dose-limiting toxicities and no significant target-mediated toxicity; a phase I study is ongoing (NCT04389632).",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sgn-b6a-an-new-vedotin-antibodydrug-conjugate-directed-to-integrin-beta-6-for-multiple-carcinoma-indications/406374/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sgn-b6a-an-new-vedotin-antibodydrug-conjugate-directed-to-integrin-beta-6-for-multiple-carcinoma-indications/406374.png","ImageObject",300,407,{"name":92,"@type":93},"Ben ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is SGN-B6A and what target does it bind?","Question",{"text":112,"@type":113},"SGN-B6A is an antibody–drug conjugate designed to deliver MMAE to cancer cells expressing integrin beta-6. Its antibody binds specifically to integrin beta-6 and does not bind other alpha-v family members.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What efficacy and preclinical evidence is reported for SGN-B6A?",{"text":117,"@type":113},"Preclinical in vivo studies show activity in models derived from non–small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. The study reports that SGN-B6A inhibits tumor growth or regresses tumor volume in multiple integrin beta-6–positive carcinoma models.",{"name":119,"@type":110,"acceptedAnswer":120},"What toxicology and safety findings were observed before clinical testing?",{"text":121,"@type":113},"In cynomolgus monkeys, dosing regimens up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},406374,1790816214,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},2336478951081,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","SGN-B6A: A New Vedotin Antibody–Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications  \nRobert P. Lyon, Mechthild Jonas, Christopher Frantz, Esther S. Trueblood, Roma Yumul, Lori Westendorf, Christopher J. Hale, Jackie L. Stilwell, Narayana Yeddula, Katie M. Snead, Vineet Kumar,  \nGabriela I. Patilea-Vrana, Kerry Klussman, and Maureen C. Ryan  \nABSTRACT  \n◥  \nIntegrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non–small cell lung, gastric, and cervical. We developed SGNB6A as an antibody–drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non–small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or6mg/kg every3weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase I first-in-human study is in progress to evaluate the safety and  \nantitumor activity ofSGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632) .  \nIntroduction  \nThe integrins are a large family of membrane-associated proteins with diverse roles in cellular adhesion, motility, and cytokinesis (1) . Functional integrins exist as heterodimers consisting of single alpha and beta chains, with18known alpha chain isoforms and8known beta chain isoforms. Within this family, integrin beta-6 (which dimerizes exclusively with isoform alpha-v) is of particular interest for its role in cancer (2, 3) . Integrin beta-6 is overexpressed in numerous solid tumors, and multiple investigators have noted its expression as a negative prognostic indicator in diverse cancers including colorectal, non–small cell lung carcinoma (NSCLC), gastric, and cervical (4–8) . Previous investigators have shown by mRNA in situ hybridization that integrin beta-6 expression is restricted to epithelial tissues in nonhuman primates (9) . This was subsequently confirmed by IHC using cryopreserved sections of both rhesus monkey and human tissues(10) .  \nSeagen Inc., Bothell, Washington.  \nCorresponding Author: Robert P. Lyon, Seagen Inc., 21823 30th Dr. SE, Bothell,  \nWA 98021 . E-mail: [rlyon@seagen.com](rlyon@seagen.com)  \n[Mol Cancer Ther 2023](Mol Cancer Ther 2023);[22:1444](22:1444)–[53](53)  \n[doi:](doi: 10.1158/1535-7163.MCT-22-0817)[ 10.1158/1535-7163.MCT-22-0817](doi: 10.1158/1535-7163.MCT-22-0817)  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.  \n􀀂2023The Authors;Published by the American Association for Cancer Research  \nWe haveverified thesefindingsand observed expression at lowlevels in epithelial cells of various tissues including the gastrointestinal tract, skin, bronchiolar epithelium of the lung, tubular epithelium of the kidney, transitional epithelium of the renal pelvis and urinary bladder, and ductal epithelium of the pancreas, breast, and salivary gland.  \nIn addition to the low constitutive expression noted above, integrin beta-6 expression is induced by tissue injury due to its role in tissue remodeling and wound repair (10), including its ability to activate TGFb (11). This role in tissue remodeling is believed to be the function that malignant cells exploit through its overexpression, allowing them to become more invasive into surrounding healthy tissue(12) . Integrin beta-","cbCaia6jNKgdO4V6","https://ap.wps.com/l/cbCaia6jNKgdO4V6","pdf",11387595,"English","# Abstract\n# Introduction\n## Integrin beta-6 expression and cancer relevance\n## Antibody–drug conjugates and vedotin payloads\n## Study rationale for SGN-B6A\n# Materials and Metho","[{\"question\":\"What is SGN-B6A and what target does it bind?\",\"answer\":\"SGN-B6A is an antibody–drug conjugate designed to deliver MMAE to cancer cells expressing integrin beta-6. Its antibody binds specifically to integrin beta-6 and does not bind other alpha-v family members.\"},{\"question\":\"What efficacy and preclinical evidence is reported for SGN-B6A?\",\"answer\":\"Preclinical in vivo studies show activity in models derived from non–small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. The study reports that SGN-B6A inhibits tumor growth or regresses tumor volume in multiple integrin beta-6–positive carcinoma models.\"},{\"question\":\"What toxicology and safety findings were observed before clinical testing?\",\"answer\":\"In cynomolgus monkeys, dosing regimens up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed.\"}]","SGN-B6A - An New Vedotin Antibody–Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications | PDF",1790565173,25]