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class="vector-toc-numb">2</span> <span>Adverse effects</span> </div> </a> <ul id="toc-Adverse_effects-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Interactions" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Interactions"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Interactions</span> </div> </a> <ul id="toc-Interactions-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Mechanism_of_action" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Mechanism_of_action"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Mechanism of action</span> </div> </a> <ul id="toc-Mechanism_of_action-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Pharmacokinetics" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Pharmacokinetics"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>Pharmacokinetics</span> </div> </a> <ul id="toc-Pharmacokinetics-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Identifying_patients_most_likely_to_respond" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Identifying_patients_most_likely_to_respond"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>Identifying patients most likely to respond</span> </div> </a> <ul id="toc-Identifying_patients_most_likely_to_respond-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Clinical_trial_history" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Clinical_trial_history"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>Clinical trial history</span> </div> </a> <button 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vector-toc-level-2"> <a class="vector-toc-link" href="#Lung_cancer"> <div class="vector-toc-text"> <span class="vector-toc-numb">7.3</span> <span>Lung cancer</span> </div> </a> <ul id="toc-Lung_cancer-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Urothelial_cancer,_including_cancer_of_the_bladder,_urethra,_ureters_and_renal_pelvis" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Urothelial_cancer,_including_cancer_of_the_bladder,_urethra,_ureters_and_renal_pelvis"> <div class="vector-toc-text"> <span class="vector-toc-numb">7.4</span> <span>Urothelial cancer, including cancer of the bladder, urethra, ureters and renal pelvis</span> </div> </a> <ul id="toc-Urothelial_cancer,_including_cancer_of_the_bladder,_urethra,_ureters_and_renal_pelvis-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Combination_trials" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Combination_trials"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>Combination trials</span> </div> </a> <button aria-controls="toc-Combination_trials-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Combination trials subsection</span> </button> <ul id="toc-Combination_trials-sublist" class="vector-toc-list"> <li id="toc-Advanced_melanoma" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Advanced_melanoma"> <div class="vector-toc-text"> <span class="vector-toc-numb">8.1</span> <span>Advanced melanoma</span> </div> </a> <ul id="toc-Advanced_melanoma-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Development" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Development"> <div class="vector-toc-text"> <span class="vector-toc-numb">9</span> <span>Development</span> </div> </a> <ul id="toc-Development-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">10</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> <span class="vector-toc-numb">11</span> <span>External links</span> </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" 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mw-first-heading"><span class="mw-page-title-main">Ipilimumab</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 17 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-17" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">17 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D8%A5%D9%8A%D8%A8%D9%8A%D9%84%D9%8A%D9%85%D9%88%D9%85%D8%A7%D8%A8" title="إيبيليموماب – Arabic" lang="ar" hreflang="ar" data-title="إيبيليموماب" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – German" lang="de" hreflang="de" data-title="Ipilimumab" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Ipilimumaab" title="Ipilimumaab – Estonian" lang="et" hreflang="et" data-title="Ipilimumaab" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target"><span>Eesti</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Spanish" lang="es" hreflang="es" data-title="Ipilimumab" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%A7%DB%8C%D9%BE%DB%8C%D9%84%DB%8C%D9%85%D9%88%D9%85%D8%A7%D8%A8" title="ایپیلیموماب – Persian" lang="fa" hreflang="fa" data-title="ایپیلیموماب" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – French" lang="fr" hreflang="fr" data-title="Ipilimumab" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Indonesian" lang="id" hreflang="id" data-title="Ipilimumab" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Italian" lang="it" hreflang="it" data-title="Ipilimumab" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E3%82%A4%E3%83%94%E3%83%AA%E3%83%A0%E3%83%9E%E3%83%96" title="イピリムマブ – Japanese" lang="ja" hreflang="ja" data-title="イピリムマブ" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Ipilimumab" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target"><span>Norsk bokmål</span></a></li><li class="interlanguage-link interwiki-or mw-list-item"><a href="https://or.wikipedia.org/wiki/%E0%AC%87%E0%AC%AA%E0%AC%BF%E0%AC%B2%E0%AC%BF%E0%AC%AE%E0%AD%81%E0%AC%AE%E0%AC%BE%E0%AC%AC" title="ଇପିଲିମୁମାବ – Odia" lang="or" hreflang="or" data-title="ଇପିଲିମୁମାବ" data-language-autonym="ଓଡ଼ିଆ" data-language-local-name="Odia" class="interlanguage-link-target"><span>ଓଡ଼ିଆ</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Polish" lang="pl" hreflang="pl" data-title="Ipilimumab" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Portuguese" lang="pt" hreflang="pt" data-title="Ipilimumab" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ru mw-list-item"><a href="https://ru.wikipedia.org/wiki/%D0%98%D0%BF%D0%B8%D0%BB%D0%B8%D0%BC%D1%83%D0%BC%D0%B0%D0%B1" title="Ипилимумаб – Russian" lang="ru" hreflang="ru" data-title="Ипилимумаб" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Slovenian" lang="sl" hreflang="sl" data-title="Ipilimumab" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target"><span>Slovenščina</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%86%D0%BF%D1%96%D0%BB%D1%96%D0%BC%D1%83%D0%BC%D0%B0%D0%B1" title="Іпілімумаб – Ukrainian" lang="uk" hreflang="uk" data-title="Іпілімумаб" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target"><span>Українська</span></a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/Ipilimumab" title="Ipilimumab – Vietnamese" lang="vi" hreflang="vi" data-title="Ipilimumab" data-language-autonym="Tiếng Việt" data-language-local-name="Vietnamese" class="interlanguage-link-target"><span>Tiếng Việt</span></a></li> </ul> <div class="after-portlet after-portlet-lang"><span class="wb-langlinks-edit wb-langlinks-link"><a href="https://www.wikidata.org/wiki/Special:EntityPage/Q2459042#sitelinks-wikipedia" title="Edit interlanguage links" class="wbc-editpage">Edit links</a></span></div> </div> </div> </div> </header> <div class="vector-page-toolbar"> <div class="vector-page-toolbar-container"> <div id="left-navigation"> <nav aria-label="Namespaces"> <div id="p-associated-pages" class="vector-menu vector-menu-tabs mw-portlet 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<div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Pharmaceutical drug</div> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox" style="border-spacing:2px;"><caption class="infobox-title"><span title="International nonproprietary name (INN): Ipilimumab">Ipilimumab</span></caption><tbody><tr><td colspan="2" class="infobox-image notheme" style="background-color: #f8f9fa;"><span class="mw-default-size" typeof="mw:File/Frameless"><a href="/wiki/File:Ipilimumab_5TRU.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/d/de/Ipilimumab_5TRU.png/220px-Ipilimumab_5TRU.png" decoding="async" width="220" height="190" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/d/de/Ipilimumab_5TRU.png/330px-Ipilimumab_5TRU.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/d/de/Ipilimumab_5TRU.png/440px-Ipilimumab_5TRU.png 2x" data-file-width="2048" data-file-height="1767" /></a></span><div class="infobox-caption"><a href="/wiki/Fragment_antigen-binding" class="mw-redirect" title="Fragment antigen-binding">Fab fragment</a> of ipilimumab (blue) binding CTLA-4 (green). From <a href="/wiki/Protein_Data_Bank" title="Protein Data Bank">PDB</a> entry <span class="plainlinks"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/pdbe/entry/pdb/5TRU">5TRU</a></span>.</div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd"><a href="/wiki/Monoclonal_antibody" title="Monoclonal antibody">Monoclonal antibody</a></th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/File:Engineered_monoclonal_antibodies.svg" title="File:Engineered monoclonal antibodies.svg">Type</a></th><td class="infobox-data">Whole antibody</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Monoclonal_antibody#Production" title="Monoclonal antibody">Source</a></th><td class="infobox-data"><a href="/wiki/Human" title="Human">Human</a></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Antigen" title="Antigen">Target</a></th><td class="infobox-data"><a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Clinical data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;">Pronunciation</th><td class="infobox-data">i pi lim′ ue mab </td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Drug_nomenclature#Trade_names" title="Drug nomenclature">Trade names</a></th><td class="infobox-data">Yervoy</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;">Other names</th><td class="infobox-data">BMS-734016,<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> MDX-010,<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> MDX-101</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/American_Society_of_Health-System_Pharmacists" title="American Society of Health-System Pharmacists">AHFS</a>/<a href="/wiki/Drugs.com" title="Drugs.com">Drugs.com</a></th><td class="infobox-data"><span title="www.drugs.com"><a rel="nofollow" class="external text" href="https://www.drugs.com/monograph/ipilimumab.html">Monograph</a></span></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/MedlinePlus" title="MedlinePlus">MedlinePlus</a></th><td class="infobox-data"><span title="medlineplus.gov"><a rel="nofollow" class="external text" href="https://medlineplus.gov/druginfo/meds/a611023.html">a611023</a></span></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">License data</a></th><td class="infobox-data"><style data-mw-deduplicate="TemplateStyles:r1126788409">.mw-parser-output .plainlist ol,.mw-parser-output .plainlist ul{line-height:inherit;list-style:none;margin:0;padding:0}.mw-parser-output .plainlist ol li,.mw-parser-output .plainlist ul li{margin-bottom:0}</style><div class="plainlist"> <ul><li><small><abbr class="country-name" title="United States">US</abbr></small> <a href="/wiki/DailyMed" title="DailyMed">DailyMed</a>: <span title="dailymed.nlm.nih.gov"><a rel="nofollow" class="external text" href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Ipilimumab">Ipilimumab</a></span></li></ul></div> </td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Pregnancy_category" title="Pregnancy category">Pregnancy<br />category</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> C</li> <li class="mw-empty-elt"></li></ul> </div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Route_of_administration" title="Route of administration">Routes of<br />administration</a></th><td class="infobox-data"><a href="/wiki/Intravenous_therapy" title="Intravenous therapy">Intravenous</a> (IV)</td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">ATC code</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><a href="/wiki/ATC_code_L01" title="ATC code L01">L01FX04</a> (<span title="www.whocc.no"><a rel="nofollow" class="external text" href="https://www.whocc.no/atc_ddd_index/?code=L01FX04">WHO</a></span>) </li></ul></div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Legal status</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Regulation_of_therapeutic_goods" title="Regulation of therapeutic goods">Legal status</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"> <ul><li><small><abbr class="country-name" title="Australia">AU</abbr>:</small> <a href="/wiki/Standard_for_the_Uniform_Scheduling_of_Medicines_and_Poisons#Schedule_4" title="Standard for the Uniform Scheduling of Medicines and Poisons">S4</a> (Prescription only)</li> <li><small><abbr class="country-name" title="Canada">CA</abbr></small>: <a href="/wiki/Prescription_drug" title="Prescription drug"> ℞-only</a> /<span class="nowrap"> </span>Schedule D<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></li> <li><small><abbr class="country-name" title="United Kingdom">UK</abbr>:</small> <a href="/wiki/Prescription_drug" title="Prescription drug">POM</a> (Prescription only)<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></li> <li><small><abbr class="country-name" title="United States">US</abbr>:</small> <a href="/wiki/Prescription_drug" title="Prescription drug">℞-only</a><sup id="cite_ref-Yervoy_FDA_label_5-0" class="reference"><a href="#cite_note-Yervoy_FDA_label-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup></li> <li><small><abbr class="country-name" title="European Union">EU</abbr>:</small> Rx-only<sup id="cite_ref-Yervoy_EPAR_6-0" class="reference"><a href="#cite_note-Yervoy_EPAR-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></li> <li>In general: ℞ (Prescription only)</li></ul></div> </td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd"><a href="/wiki/Pharmacokinetics" title="Pharmacokinetics">Pharmacokinetic</a> data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Biological_half-life" title="Biological half-life">Elimination <span class="nowrap">half-life</span></a></th><td class="infobox-data">15 days<sup id="cite_ref-DrugBank_7-0" class="reference"><a href="#cite_note-DrugBank-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Identifiers</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/CAS_Registry_Number" title="CAS Registry Number">CAS Number</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="commonchemistry.cas.org"><a rel="nofollow" class="external text" href="https://commonchemistry.cas.org/detail?cas_rn=477202-00-9">477202-00-9</a></span><sup> <span typeof="mw:File"><span><img alt="☒" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/7px-X_mark.svg.png" decoding="async" width="7" height="8" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/11px-X_mark.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/14px-X_mark.svg.png 2x" data-file-width="525" data-file-height="600" /></span></span><span style="display:none">N</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/DrugBank" title="DrugBank">DrugBank</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.drugbank.ca"><a rel="nofollow" class="external text" href="https://www.drugbank.ca/drugs/DB06186">DB06186</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ChemSpider" title="ChemSpider">ChemSpider</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li>none</li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Unique_Ingredient_Identifier" title="Unique Ingredient Identifier">UNII</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="precision.fda.gov"><a rel="nofollow" class="external text" href="https://precision.fda.gov/uniisearch/srs/unii/6T8C155666">6T8C155666</a></span></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/KEGG" title="KEGG">KEGG</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.kegg.jp"><a rel="nofollow" class="external text" href="https://www.kegg.jp/entry/D04603">D04603</a></span><sup> <span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup></li></ul></div></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/ChEMBL" title="ChEMBL">ChEMBL</a></th><td class="infobox-data"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1126788409"><div class="plainlist"><ul><li><span title="www.ebi.ac.uk"><a rel="nofollow" class="external text" href="https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/ChEMBL1789844">ChEMBL1789844</a></span></li></ul></div></td></tr><tr><th colspan="2" class="infobox-header" style="background:#ddd">Chemical and physical data</th></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Chemical_formula" title="Chemical formula">Formula</a></th><td class="infobox-data"><span title="Carbon">C</span><sub>6742</sub><span title="Hydrogen">H</span><sub>9972</sub><span title="Nitrogen">N</span><sub>1732</sub><span title="Oxygen">O</span><sub>2004</sub><span title="Sulfur">S</span><sub>40</sub></td></tr><tr><th scope="row" class="infobox-label" style="line-height:1.2em;"><a href="/wiki/Molar_mass" title="Molar mass">Molar mass</a></th><td class="infobox-data"><span class="nowrap"><span data-sort-value="7005148634460000000♠"></span>148<span style="margin-left:.25em;">634</span>.46</span> g·mol<sup>−1</sup></td></tr><tr><td colspan="2" class="infobox-below"><style data-mw-deduplicate="TemplateStyles:r886047488">.mw-parser-output .nobold{font-weight:normal}</style><span class="nobold"> <sup><span typeof="mw:File"><span><img alt="☒" src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/7px-X_mark.svg.png" decoding="async" width="7" height="8" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/11px-X_mark.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a2/X_mark.svg/14px-X_mark.svg.png 2x" data-file-width="525" data-file-height="600" /></span></span><span style="display:none">N</span><span typeof="mw:File"><span><img alt="check" src="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png" decoding="async" width="7" height="7" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/11px-Yes_check.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/14px-Yes_check.svg.png 2x" data-file-width="600" data-file-height="600" /></span></span><span style="display:none">Y</span></sup> <a href="/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validation" title="Wikipedia:WikiProject Chemicals/Chembox validation">(what is this?)</a></span><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r886047488"><span class="nobold">  <span class="reflink plainlinks nourlexpansion"><a class="external text" href="https://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=458270765&page2=Ipilimumab">(verify)</a></span></span></td></tr></tbody></table> <p><b>Ipilimumab</b>, sold under the brand name <b>Yervoy</b>, is a <a href="/wiki/Monoclonal_antibody" title="Monoclonal antibody">monoclonal antibody</a> medication that works to activate the <a href="/wiki/Immune_system" title="Immune system">immune system</a> by targeting <a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a>, a protein receptor that downregulates the immune system. </p><p><a href="/wiki/Cytotoxic_T_lymphocytes" class="mw-redirect" title="Cytotoxic T lymphocytes">Cytotoxic T lymphocytes</a> (CTLs) can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction.<sup id="cite_ref-pmid29208439_8-0" class="reference"><a href="#cite_note-pmid29208439-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Ipilimumab turns off this inhibitory mechanism and boosts the body's immune response against cancer cells.<sup id="cite_ref-pmid29208439_8-1" class="reference"><a href="#cite_note-pmid29208439-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Ribas_9-0" class="reference"><a href="#cite_note-Ribas-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p>Ipilimumab was approved by the US <a href="/wiki/Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a> (FDA) in March 2011, for the treatment of melanoma, renal cell carcinoma (RCC), colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma, esophageal cancer.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-FDA_approval_package_11-0" class="reference"><a href="#cite_note-FDA_approval_package-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-NYT-20150529_13-0" class="reference"><a href="#cite_note-NYT-20150529-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> It is undergoing<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items" title="Wikipedia:Manual of Style/Dates and numbers"><span title="The time period mentioned near this tag is ambiguous. (October 2020)">when?</span></a></i>]</sup> <a href="/wiki/Clinical_trial" title="Clinical trial">clinical trials</a> for the treatment of <a href="/wiki/Bladder_cancer" title="Bladder cancer">bladder cancer</a><sup id="cite_ref-NCT991_14-0" class="reference"><a href="#cite_note-NCT991-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> and metastatic hormone-refractory <a href="/wiki/Prostate_cancer" title="Prostate cancer">prostate cancer</a>.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p><p>The concept of using anti-CTLA4 antibodies to treat cancer was first developed by <a href="/wiki/James_P._Allison" title="James P. Allison">James P. Allison</a> while he was director of the Cancer Research Laboratory at the <a href="/wiki/University_of_California,_Berkeley" title="University of California, Berkeley">University of California, Berkeley</a>.<sup id="cite_ref-auto_16-0" class="reference"><a href="#cite_note-auto-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> Clinical development of anti-CTLA4 was initiated by <a href="/wiki/Medarex" title="Medarex">Medarex</a>, which was later acquired by <a href="/wiki/Bristol-Myers_Squibb" class="mw-redirect" title="Bristol-Myers Squibb">Bristol-Myers Squibb</a>. For his work in developing ipilimumab, Allison was awarded the <a href="/wiki/Lasker_Award" title="Lasker Award">Lasker Award</a> in 2015.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> Allison later was the co-winner of the 2018 <a href="/wiki/Nobel_Prize_in_Physiology_or_Medicine" title="Nobel Prize in Physiology or Medicine">Nobel Prize in Physiology or Medicine</a>.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Medical_uses">Medical uses</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=1" title="Edit section: Medical uses"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Ipilimumab was approved by the U.S. <a href="/wiki/Food_and_Drug_Administration" title="Food and Drug Administration">Food and Drug Administration</a> (FDA) in March 2011, to treat people with late-stage melanoma that has spread or cannot be removed by surgery.<sup id="cite_ref-pmid29208439_8-2" class="reference"><a href="#cite_note-pmid29208439-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-FDA_approval_package_11-1" class="reference"><a href="#cite_note-FDA_approval_package-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-FDA_PR_20110325_20-0" class="reference"><a href="#cite_note-FDA_PR_20110325-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Drugs.com_22-0" class="reference"><a href="#cite_note-Drugs.com-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> It was later approved by the US FDA on October 28, 2015, for stage 3 patients as <a href="/wiki/Adjuvant_therapy" title="Adjuvant therapy">adjuvant therapy</a>.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> On February 1, 2012, <a href="/wiki/Health_Canada" title="Health Canada">Health Canada</a> approved ipilimumab for "treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease."<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> Ipilimumab was approved in the European Union (EU), for second line treatment of metastatic melanoma in November 2012.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Nivolumab" title="Nivolumab">Nivolumab</a>, in combination with ipilimumab is indicated for the treatment of intermediate or poor risk, previously untreated advanced <a href="/wiki/Renal_cell_carcinoma" title="Renal cell carcinoma">renal cell carcinoma</a>.<sup id="cite_ref-Yervoy_FDA_label_5-1" class="reference"><a href="#cite_note-Yervoy_FDA_label-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> </p><p>Ipilimumab, in combination with nivolumab, is indicated for the treatment of adults and adolescents twelve years and older with <a href="/wiki/Microsatellite_instability" title="Microsatellite instability">microsatellite instability</a>-high or <a href="/wiki/Mismatch_repair_cancer_syndrome" title="Mismatch repair cancer syndrome">mismatch repair deficient</a> metastatic <a href="/wiki/Colorectal_cancer" title="Colorectal cancer">colorectal cancer</a> that has progressed following treatment with a <a href="/wiki/Fluoropyrimidine" title="Fluoropyrimidine">fluoropyrimidine</a>, <a href="/wiki/Oxaliplatin" title="Oxaliplatin">oxaliplatin</a>, and <a href="/wiki/Irinotecan" title="Irinotecan">irinotecan</a>.<sup id="cite_ref-Yervoy_FDA_label_5-2" class="reference"><a href="#cite_note-Yervoy_FDA_label-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p><p>Ipilimumab, in combination with nivolumab, is indicated for the treatment of people with <a href="/wiki/Hepatocellular_carcinoma" title="Hepatocellular carcinoma">hepatocellular carcinoma</a> who have been previously treated with <a href="/wiki/Sorafenib" title="Sorafenib">sorafenib</a>.<sup id="cite_ref-Yervoy_FDA_label_5-3" class="reference"><a href="#cite_note-Yervoy_FDA_label-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> </p><p>Ipilimumab, in combination with nivolumab, is indicated for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test.<sup id="cite_ref-Yervoy_FDA_label_5-4" class="reference"><a href="#cite_note-Yervoy_FDA_label-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> </p><p>In October 2020, the U.S. FDA approved the combination of nivolumab with ipilimumab for the first-line treatment of adults with <a href="/wiki/Malignant_pleural_mesothelioma" class="mw-redirect" title="Malignant pleural mesothelioma">malignant pleural mesothelioma</a> that cannot be removed by surgery.<sup id="cite_ref-FDA_PR_20201002_32-0" class="reference"><a href="#cite_note-FDA_PR_20201002-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> This is the first drug regimen approved for mesothelioma in sixteen years and the second FDA-approved systemic therapy for mesothelioma.<sup id="cite_ref-FDA_PR_20201002_32-1" class="reference"><a href="#cite_note-FDA_PR_20201002-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Adverse_effects">Adverse effects</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=2" title="Edit section: Adverse effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1251242444">.mw-parser-output .ambox{border:1px solid #a2a9b1;border-left:10px solid #36c;background-color:#fbfbfb;box-sizing:border-box}.mw-parser-output .ambox+link+.ambox,.mw-parser-output .ambox+link+style+.ambox,.mw-parser-output .ambox+link+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+style+.ambox,.mw-parser-output .ambox+.mw-empty-elt+link+link+.ambox{margin-top:-1px}html body.mediawiki .mw-parser-output .ambox.mbox-small-left{margin:4px 1em 4px 0;overflow:hidden;width:238px;border-collapse:collapse;font-size:88%;line-height:1.25em}.mw-parser-output .ambox-speedy{border-left:10px solid #b32424;background-color:#fee7e6}.mw-parser-output .ambox-delete{border-left:10px solid #b32424}.mw-parser-output .ambox-content{border-left:10px solid #f28500}.mw-parser-output .ambox-style{border-left:10px solid #fc3}.mw-parser-output .ambox-move{border-left:10px solid #9932cc}.mw-parser-output .ambox-protection{border-left:10px solid #a2a9b1}.mw-parser-output .ambox .mbox-text{border:none;padding:0.25em 0.5em;width:100%}.mw-parser-output .ambox .mbox-image{border:none;padding:2px 0 2px 0.5em;text-align:center}.mw-parser-output .ambox .mbox-imageright{border:none;padding:2px 0.5em 2px 0;text-align:center}.mw-parser-output .ambox .mbox-empty-cell{border:none;padding:0;width:1px}.mw-parser-output .ambox .mbox-image-div{width:52px}@media(min-width:720px){.mw-parser-output .ambox{margin:0 10%}}@media print{body.ns-0 .mw-parser-output .ambox{display:none!important}}</style><table class="box-Expand_section plainlinks metadata ambox mbox-small-left ambox-content" role="presentation"><tbody><tr><td class="mbox-image"><span typeof="mw:File"><a href="/wiki/File:Wiki_letter_w_cropped.svg" class="mw-file-description"><img alt="[icon]" src="//upload.wikimedia.org/wikipedia/commons/thumb/1/1c/Wiki_letter_w_cropped.svg/20px-Wiki_letter_w_cropped.svg.png" decoding="async" width="20" height="14" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/1c/Wiki_letter_w_cropped.svg/30px-Wiki_letter_w_cropped.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/1c/Wiki_letter_w_cropped.svg/40px-Wiki_letter_w_cropped.svg.png 2x" data-file-width="44" data-file-height="31" /></a></span></td><td class="mbox-text"><div class="mbox-text-span">This section <b>needs expansion</b>. You can help by <a class="external text" href="https://en.wikipedia.org/w/index.php?title=Ipilimumab&action=edit&section=">adding to it</a>. <span class="date-container"><i>(<span class="date">March 2016</span>)</i></span></div></td></tr></tbody></table> <p>A major drawback of ipilimumab therapy is its association with severe and potentially fatal immunological adverse effects due to <a href="/wiki/T_cell_activation" class="mw-redirect" title="T cell activation">T cell activation</a> and proliferation, occurring in ten to twenty percent of patients.<sup id="cite_ref-2015therAdvRev_33-0" class="reference"><a href="#cite_note-2015therAdvRev-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> Serious adverse effects include stomach pain, bloating, constipation, diarrhea, fever, trouble breathing, and urinating problems. A "risk evaluation and mitigation strategy" informs prescribers of the potential risks.<sup id="cite_ref-Drugs.com_22-1" class="reference"><a href="#cite_note-Drugs.com-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p><p>Between 5.7 and 9.1% of individuals treated with ipilimumab develop <a href="/wiki/Checkpoint_inhibitor_induced_colitis" title="Checkpoint inhibitor induced colitis">checkpoint inhibitor induced colitis</a>.<sup id="cite_ref-Bella_35-0" class="reference"><a href="#cite_note-Bella-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p><p>Individual cases of severe neurologic disorders following ipilimumab have been observed, including acute inflammatory <a href="/wiki/Demyelination" class="mw-redirect" title="Demyelination">demyelination</a> <a href="/wiki/Polyneuropathy" title="Polyneuropathy">polyneuropathy</a> and an ascending <a href="/wiki/Motor_paralysis" class="mw-redirect" title="Motor paralysis">motor paralysis</a>, and <a href="/wiki/Myasthenia_gravis" title="Myasthenia gravis">myasthenia gravis</a>.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Interactions">Interactions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=3" title="Edit section: Interactions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The combination of ipilimumab with either <a href="/wiki/Leflunomide" title="Leflunomide">leflunomide</a> or <a href="/wiki/Vemurafenib" title="Vemurafenib">vemurafenib</a> may lead to increased <a href="/wiki/Hepatotoxicity" title="Hepatotoxicity">hepatotoxicity</a>.<sup id="cite_ref-Leflunomide_package_insert_37-0" class="reference"><a href="#cite_note-Leflunomide_package_insert-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Package_insert_40-0" class="reference"><a href="#cite_note-Package_insert-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p><p>Systemic <a href="/wiki/Corticosteroids" class="mw-redirect" title="Corticosteroids">corticosteroids</a> should be avoided before starting ipilimumab; however, systemic corticosteroids may be used to treat an immune-related <a href="/wiki/Adverse_reaction" class="mw-redirect" title="Adverse reaction">adverse reaction</a> that arises from ipilimumab treatment.<sup id="cite_ref-European_product_information_41-0" class="reference"><a href="#cite_note-European_product_information-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> </p><p>Patients taking <a href="/wiki/Anticoagulants" class="mw-redirect" title="Anticoagulants">anticoagulants</a> with ipilimumab should be monitored due to an increased risk of <a href="/wiki/Gastrointestinal_bleeding" title="Gastrointestinal bleeding">gastrointestinal bleeding</a>.<sup id="cite_ref-European_product_information_41-1" class="reference"><a href="#cite_note-European_product_information-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Mechanism_of_action">Mechanism of action</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=4" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>T lymphocytes can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction. Ipilimumab turns off this inhibitory mechanism and allows the lymphocytes to continue to destroy cancer cells.<sup id="cite_ref-Ribas_9-1" class="reference"><a href="#cite_note-Ribas-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p>Cancer cells produce antigens, which the immune system can use to identify them. These antigens are recognized by <a href="/wiki/Dendritic_cells" class="mw-redirect" title="Dendritic cells">dendritic cells</a> that present the antigens to <a href="/wiki/Cytotoxic_T_lymphocytes" class="mw-redirect" title="Cytotoxic T lymphocytes">cytotoxic T lymphocytes</a> (CTLs) in the <a href="/wiki/Lymph_nodes" class="mw-redirect" title="Lymph nodes">lymph nodes</a>. The CTLs recognize the cancer cells by those antigens and destroy them. However, along with the antigens, the dendritic cells present an inhibitory signal. That signal binds to a receptor, cytotoxic T lymphocyte-associated antigen 4 (<a href="/wiki/CTLA-4" class="mw-redirect" title="CTLA-4">CTLA-4</a>), on the CTL and turns off the cytotoxic reaction. This allows the cancer cells to survive.<sup id="cite_ref-Ribas_9-2" class="reference"><a href="#cite_note-Ribas-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p><p>Ipilimumab binds to CTLA-4, blocking the inhibitory signal, which allows the CTLs to destroy the cancer cells.<sup id="cite_ref-Ribas_9-3" class="reference"><a href="#cite_note-Ribas-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid20616954_42-0" class="reference"><a href="#cite_note-pmid20616954-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid19648604_43-0" class="reference"><a href="#cite_note-pmid19648604-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-46" class="reference"><a href="#cite_note-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-47" class="reference"><a href="#cite_note-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> In 2014 a study indicated that the antibody works by allowing the patients' T cells to target a greater variety of antigens rather than by increasing the number attacking a single antigen.<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Pharmacokinetics">Pharmacokinetics</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=5" title="Edit section: Pharmacokinetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The <a href="/wiki/Elimination_half-life" class="mw-redirect" title="Elimination half-life">elimination half-life</a> of ipilimumab is about 15<span class="nowrap"> </span>days.<sup id="cite_ref-DrugBank_7-1" class="reference"><a href="#cite_note-DrugBank-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Identifying_patients_most_likely_to_respond">Identifying patients most likely to respond</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=6" title="Edit section: Identifying patients most likely to respond"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>During "cancer immunoediting", tumor cells can produce antigens that provoke a reduced immune response and/or establish an immunosuppressive <a href="/wiki/Tumor_microenvironment" title="Tumor microenvironment">tumor microenvironment</a> (TME). The latter can arise as a consequence of repeated, ineffective T cell stimulation. This triggers the <a href="/wiki/Immune_checkpoint" title="Immune checkpoint">checkpoint</a> that ipilumumab targets. Many patients do not benefit from treatment, which may be related to reduced mutation load and/or missense point mutation-derived neoantigens.<sup id="cite_ref-pmid29208439_8-3" class="reference"><a href="#cite_note-pmid29208439-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Tumor antigens can either be improperly expressed normal proteins or abnormal proteins with tumor-specific expression. Somatic cancer mutations can produce "nonself" tumor-specific mutant antigens (neoantigens).<sup id="cite_ref-Gubin_2015_49-0" class="reference"><a href="#cite_note-Gubin_2015-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> </p><p>Sequencing and <a href="/wiki/Epitope" title="Epitope">epitope</a> prediction algorithms identified neoantigens in mouse tumors that functioned as tumor-specific T cell targets. Neoantigens were recognized by T cells in melanoma patients and were likely the major contributor to positive clinical effects of <a href="/wiki/Adoptive_cell_transfer" title="Adoptive cell transfer">adoptive cell transfer</a>. Mouse models established that neoantigens were the targets of T cells activated by checkpoint blockade therapy and that synthetic long <a href="/wiki/Peptides" class="mw-redirect" title="Peptides">peptides</a> comprising these neoantigens were effective when administered as vaccines with CTLA-4 and/or PD-1 mAbs. Cancers with higher mutation burdens, and an associated likelihood of expressing neoantigens, appear most likely to respond to checkpoint therapy.<sup id="cite_ref-pmid29208439_8-4" class="reference"><a href="#cite_note-pmid29208439-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> In melanoma and certain other cancers, the numbers of mutations and neoantigens correlate with patient response. Increased PD ligand 2 (PD-L2) transcript expression and an immune "cytolytic" <a href="/wiki/Gene_signature" title="Gene signature">gene signature</a> also correlated with neoantigen load and tumor response. CTLA-4 expression was a response indicator, which along with PD-L2 were likely expressed in <a href="/wiki/Tumor-infiltrating_immune_cell" class="mw-redirect" title="Tumor-infiltrating immune cell">tumor-infiltrating immune cells</a>. An inflamed TME prior to treatment is also associated with response.<sup id="cite_ref-Gubin_2015_49-1" class="reference"><a href="#cite_note-Gubin_2015-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> </p><p>Nearly all neoantigens in one study were patient-specific and most likely reflected mutations that do not directly contribute to tumorigenesis. However, none revealed features or motifs exclusive to responders.<sup id="cite_ref-Gubin_2015_49-2" class="reference"><a href="#cite_note-Gubin_2015-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Clinical_trial_history">Clinical trial history</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=7" title="Edit section: Clinical trial history"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the 2000s, ipilimumab clinical trials were under way on patients with melanoma, <a href="/wiki/Renal_cell_carcinoma" title="Renal cell carcinoma">renal cell carcinoma</a>, prostate cancers, <a href="/wiki/Urothelial_carcinoma" class="mw-redirect" title="Urothelial carcinoma">urothelial carcinoma</a> and <a href="/wiki/Ovarian_cancer" title="Ovarian cancer">ovarian cancer</a>.<sup id="cite_ref-sa15_50-0" class="reference"><a href="#cite_note-sa15-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> By 2007, there were two fully human anti CTLA-4<sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> monoclonal antibodies in advanced clinical trials. Ipilimumab, which is an <a href="/wiki/Immunoglobulin_G" title="Immunoglobulin G">IgG1</a> isotype, and <a href="/wiki/Tremelimumab" title="Tremelimumab">tremelimumab</a> (from Pfizer) which is an IgG2 isotype.<sup id="cite_ref-pmid19088949_52-0" class="reference"><a href="#cite_note-pmid19088949-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid19052265_53-0" class="reference"><a href="#cite_note-pmid19052265-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Melanoma">Melanoma</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=8" title="Edit section: Melanoma"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>On December 10, 2007, Bristol-Myers Squibb and Medarex released the results of three studies on ipilimumab for melanoma.<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> The three studies tested 487 patients with advanced skin cancer. One of the three studies failed to meet its primary goal of shrinking tumors in at least 10.0% of the study's 155 patients. Side effects included rashes, diarrhea, and hepatitis. </p><p>In 2010, a study was presented that showed a median survival of ten months in advanced melanoma patients treated with ipilimumab, compared with 6.4 months for those treated with <a href="/wiki/Gp100:209-217(210M)" title="Gp100:209-217(210M)">gp100</a>, an experimental vaccine (n=676), and 10.1 months for those treated with both the vaccine and ipilimumab.<sup id="cite_ref-PMID20525992_55-0" class="reference"><a href="#cite_note-PMID20525992-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup> The Phase III clinical studies on the drug were controversial for their unconventional use of a control arm (as opposed to using a placebo or standard treatment). Ipilimumab gained FDA approval in March 2011.<sup id="cite_ref-FDA_approval_package_11-2" class="reference"><a href="#cite_note-FDA_approval_package-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-FDA_PR_20110325_20-1" class="reference"><a href="#cite_note-FDA_PR_20110325-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Prostate_cancer">Prostate cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=9" title="Edit section: Prostate cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In 2008/09 Medarex performed a phase I/II dose escalation clinical trial of ipilimumab in metastatic <a href="/wiki/Hormone-refractory_prostate_cancer" class="mw-redirect" title="Hormone-refractory prostate cancer">hormone-refractory prostate cancer</a> (HRPC). Some of the patients with advanced prostate cancer had their tumors drastically shrink, promoting further trials.<sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup> </p><p>On June 19, 2009, the Mayo Clinic reported two prostate cancer patients involved in a phase II study using MDX-010 therapy who had been told initially that their condition was inoperable but had their tumors shrunk by the drug such that operation was possible and are now cancer-free as a result.<sup id="cite_ref-57" class="reference"><a href="#cite_note-57"><span class="cite-bracket">[</span>57<span class="cite-bracket">]</span></a></sup> This press report however was criticized as premature and somewhat inaccurate. The clinical trials were still at an early stage and were run alongside other treatments – which could have been the real explanation for the tumor shrinkage.<sup id="cite_ref-58" class="reference"><a href="#cite_note-58"><span class="cite-bracket">[</span>58<span class="cite-bracket">]</span></a></sup> It was too early to say whether ipilimumab made any difference.<sup id="cite_ref-59" class="reference"><a href="#cite_note-59"><span class="cite-bracket">[</span>59<span class="cite-bracket">]</span></a></sup> </p><p>In 2016, a phase II study using ipilimumab and <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> in AR-V7-expressing metastatic castration-resistant prostate cancer was opened.<sup id="cite_ref-60" class="reference"><a href="#cite_note-60"><span class="cite-bracket">[</span>60<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Silberstein_2016_61-0" class="reference"><a href="#cite_note-Silberstein_2016-61"><span class="cite-bracket">[</span>61<span class="cite-bracket">]</span></a></sup> <a href="/wiki/AR-V7" class="mw-redirect" title="AR-V7">AR-V7</a> is an <a href="/wiki/Androgen_receptor" title="Androgen receptor">androgen receptor</a> <a href="/wiki/Splice_variant" class="mw-redirect" title="Splice variant">splice variant</a> that can be detected in circulating tumor cells of metastatic prostate cancer patients.<sup id="cite_ref-Silberstein_2016_61-1" class="reference"><a href="#cite_note-Silberstein_2016-61"><span class="cite-bracket">[</span>61<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-62" class="reference"><a href="#cite_note-62"><span class="cite-bracket">[</span>62<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Lung_cancer">Lung cancer</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=10" title="Edit section: Lung cancer"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>CHECKMATE-227 <sup id="cite_ref-Hellmann_2019_63-0" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> tested the combination of <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> and ipilimumab in patients with stage IV or recurrent NSCLC without previous treatment.<sup id="cite_ref-Nasser_2020_64-0" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-1" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> Patients with a PD-L1 expression level of 1% or more were randomized in a 1:1:1 ratio to receive <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> plus ipilimumab, nivolumab alone, or chemotherapy.<sup id="cite_ref-Nasser_2020_64-1" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-2" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> The chemotherapy used was cisplatin or carboplatin, combined with gemcitabine for patient with squamous cell NSCLC, or pemetrexed for patients with nonsquamous disease.<sup id="cite_ref-Nasser_2020_64-2" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-3" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> The overall survival was 17.1, 15.7 and 14.9 months, respectively.<sup id="cite_ref-Nasser_2020_64-3" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-4" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> plus ipilimumab, <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> plus chemotherapy, or chemotherapy.<sup id="cite_ref-Nasser_2020_64-4" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-5" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> The OS was 17.2, 15.2 and 12.2 months, respectively.<sup id="cite_ref-Nasser_2020_64-5" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Hellmann_2019_63-6" class="reference"><a href="#cite_note-Hellmann_2019-63"><span class="cite-bracket">[</span>63<span class="cite-bracket">]</span></a></sup> </p><p>CHECKMATE-9LA <sup id="cite_ref-Reck_2020_65-0" class="reference"><a href="#cite_note-Reck_2020-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> randomized patients with stage IV NSCLC, to <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a> 360 mg Q3W + ipilimumab 1 mg/kg Q6W + two cycles of chemotherapy or 4 cycles of chemotherapy alone.<sup id="cite_ref-Nasser_2020_64-6" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup> The chemotherapy used was Cisplatin or Carboplatin combined with Pemetrexed or Paclitaxel. The data were presented in an abstract format and as a lecture during the American Society of Clinical Oncology (ASCO) 2020 annual meeting.<sup id="cite_ref-Reck_2020_65-1" class="reference"><a href="#cite_note-Reck_2020-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup> Median OS was 15.6 and 10.9 months, in the immunotherapy-chemotherapy and the chemotherapy only groups, respectively.<sup id="cite_ref-Reck_2020_65-2" class="reference"><a href="#cite_note-Reck_2020-65"><span class="cite-bracket">[</span>65<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Nasser_2020_64-7" class="reference"><a href="#cite_note-Nasser_2020-64"><span class="cite-bracket">[</span>64<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Urothelial_cancer,_including_cancer_of_the_bladder,_urethra,_ureters_and_renal_pelvis"><span id="Urothelial_cancer.2C_including_cancer_of_the_bladder.2C_urethra.2C_ureters_and_renal_pelvis"></span>Urothelial cancer, including cancer of the bladder, urethra, ureters and renal pelvis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=11" title="Edit section: Urothelial cancer, including cancer of the bladder, urethra, ureters and renal pelvis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>A Phase 2 clinical trial entitled <a rel="nofollow" class="external text" href="https://clinicaltrials.gov/ct2/show/results/NCT01524991">First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma</a> was first reported in 2015 <sup id="cite_ref-66" class="reference"><a href="#cite_note-66"><span class="cite-bracket">[</span>66<span class="cite-bracket">]</span></a></sup> Thirty-six patients were treated with chemotherapy, adding ipilimumab after the second 21-day cycle. Though the study did not meet its primary endpoint, a significant expansion of circulating CD4 cells was noted upon addition of ipilimumab, which correlated with improved survival, especially in patients with deleterious somatic DNA damage response mutations.<sup id="cite_ref-67" class="reference"><a href="#cite_note-67"><span class="cite-bracket">[</span>67<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Combination_trials">Combination trials</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=12" title="Edit section: Combination trials"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Advanced_melanoma">Advanced melanoma</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=13" title="Edit section: Advanced melanoma"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>To increase response rate and reduce adverse reactions, various drug combinations are being tested. </p><p>In 2013, a trial was running that compared ipilimumab alone against ipilimumab in combination with <a href="/wiki/Nivolumab" title="Nivolumab">nivolumab</a>. The response rate (tumours shrinking by at least 30%) was 58% for the combination, 44% for nivolumab alone, and 19% for ipilimumab alone.<sup id="cite_ref-68" class="reference"><a href="#cite_note-68"><span class="cite-bracket">[</span>68<span class="cite-bracket">]</span></a></sup> This combination gained FDA approval for melanoma in October 2015. </p><p>In March 2014, an open-label, randomized, two agent, single center trial started combining ipilimumab with <a href="/wiki/Phosphatidylserine" title="Phosphatidylserine">phosphatidylserine</a>-targeting immunotherapy <a href="/wiki/Bavituximab" title="Bavituximab">bavituximab</a> for the treatment of advanced melanoma. The number of treated patients in arm A (ipilimumab plus bavituximab) was to be 16, with 8 in arm B (ipilimumab only).<sup id="cite_ref-69" class="reference"><a href="#cite_note-69"><span class="cite-bracket">[</span>69<span class="cite-bracket">]</span></a></sup> The trial was terminated in April 2016 due to low enrollment.<sup id="cite_ref-70" class="reference"><a href="#cite_note-70"><span class="cite-bracket">[</span>70<span class="cite-bracket">]</span></a></sup> Previous, preclinical studies showed that PS targeting antibodies (such as bavituximab) enhance the anti-tumor activity of anti-CTLA-4 and anti-PD-1 antibodies. Tumor growth inhibition correlates with infiltration of immune cells in tumors and induction of adaptive immunity. The combination of these mechanisms promotes strong, localized, anti-tumor responses without the side-effects of systemic immune activation.<sup id="cite_ref-71" class="reference"><a href="#cite_note-71"><span class="cite-bracket">[</span>71<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Development">Development</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=14" title="Edit section: Development"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Following the 1987 cloning of CTLA-4 in mice,<sup id="cite_ref-72" class="reference"><a href="#cite_note-72"><span class="cite-bracket">[</span>72<span class="cite-bracket">]</span></a></sup> its conservation in humans and similarities with <a href="/wiki/CD28" title="CD28">CD28</a> were soon noticed.<sup id="cite_ref-73" class="reference"><a href="#cite_note-73"><span class="cite-bracket">[</span>73<span class="cite-bracket">]</span></a></sup> CD28 at that time was a recently identified "T cell costimulatory" molecule important for T cell activation.<sup id="cite_ref-74" class="reference"><a href="#cite_note-74"><span class="cite-bracket">[</span>74<span class="cite-bracket">]</span></a></sup> Anti-CTLA-4 blockade, the invention that gave rise to ipilimumab, was conceived by <a href="/wiki/James_P._Allison" title="James P. Allison">Allison</a> and <a href="/wiki/Matthew_Krummel" title="Matthew Krummel">Krummel</a> along with CTLA-4's inhibitory role in T cell activation.<sup id="cite_ref-75" class="reference"><a href="#cite_note-75"><span class="cite-bracket">[</span>75<span class="cite-bracket">]</span></a></sup> They were able to demonstrate that CTLA-4 signaling in T cells inhibited T cell responses.<sup id="cite_ref-76" class="reference"><a href="#cite_note-76"><span class="cite-bracket">[</span>76<span class="cite-bracket">]</span></a></sup> They then injected intact antibodies and demonstrated that CTLA-4 blockade enhanced T cell responses in mice responding to vaccines and to <a href="/wiki/Super-antigens" class="mw-redirect" title="Super-antigens">super antigens</a>.<sup id="cite_ref-77" class="reference"><a href="#cite_note-77"><span class="cite-bracket">[</span>77<span class="cite-bracket">]</span></a></sup> Leach, a new postdoctoral fellow, was tasked by Allison with applying these in tumor models. Antibody-treated mice showed significantly less cancer growth than the controls.<sup id="cite_ref-auto_16-1" class="reference"><a href="#cite_note-auto-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p><p>Bluestone and Linsley separately studied the similarities between CD28 and CTLA-4. Bluestone's lab published studies, one together with Krummel and Allison, for <i>in vitro</i> studies of CTLA-4 function.<sup id="cite_ref-78" class="reference"><a href="#cite_note-78"><span class="cite-bracket">[</span>78<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-79" class="reference"><a href="#cite_note-79"><span class="cite-bracket">[</span>79<span class="cite-bracket">]</span></a></sup> In collaboration with Mark Jenkins, they were able to see effects of anti-CTLA-4 antibodies <i>in vivo</i> in an immunization setting,<sup id="cite_ref-80" class="reference"><a href="#cite_note-80"><span class="cite-bracket">[</span>80<span class="cite-bracket">]</span></a></sup> but did not effectively carry this into tumor biology. Linsley and colleagues had made antibodies against CTLA-4 three years prior to those of Krummel/Allison or Walunas/Bluestone. They concluded that the molecule functioned similarly to CD28 and was a "positive costimulator".<sup id="cite_ref-81" class="reference"><a href="#cite_note-81"><span class="cite-bracket">[</span>81<span class="cite-bracket">]</span></a></sup> They apparently did not pursue CTLA-4 tumor targeting, although BMS licensed the Allison/Leach/Krummel patent through their acquisition of Medarex and the fully humanized antibody MDX010, which later became ipilimumab. </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=15" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="http://www.biocentury.com/products/bms-734016">"Yervoy, ipilimumab (BMS-734016) - Product Profile - BioCentury"</a>. <i>BioCentury Online Intelligence</i>. BioCentury Publications<span class="reference-accessdate">. Retrieved <span class="nowrap">11 August</span> 2016</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=BioCentury+Online+Intelligence&rft.atitle=Yervoy%2C+ipilimumab+%28BMS-734016%29+-+Product+Profile+-+BioCentury&rft_id=http%3A%2F%2Fwww.biocentury.com%2Fproducts%2Fbms-734016&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" class="Z3988"></span></span> </li> <li id="cite_note-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-2">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFUSAN" class="citation pressrelease cs1">USAN. <a rel="nofollow" class="external text" href="https://web.archive.org/web/20160223223857/http://www.ama-assn.org/resources/doc/usan/ipilimumab2.doc">"STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL - ipilimumab"</a> (Press release). <a href="/wiki/American_Medical_Association" title="American Medical Association">American Medical Association</a> (AMA). 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title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Immunity&rft.atitle=CTLA-4+can+function+as+a+negative+regulator+of+T+cell+activation&rft.volume=1&rft.issue=5&rft.pages=405-413&rft.date=1994-08&rft_id=info%3Adoi%2F10.1016%2F1074-7613%2894%2990071-x&rft_id=info%3Apmid%2F7882171&rft.aulast=Walunas&rft.aufirst=TL&rft.au=Lenschow%2C+DJ&rft.au=Bakker%2C+CY&rft.au=Linsley%2C+PS&rft.au=Freeman%2C+GJ&rft.au=Green%2C+JM&rft.au=Thompson%2C+CB&rft.au=Bluestone%2C+JA&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" class="Z3988"></span></span> </li> <li id="cite_note-80"><span class="mw-cite-backlink"><b><a href="#cite_ref-80">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKearneyWalunasKarrMorton1995" class="citation journal cs1">Kearney ER, Walunas TL, Karr RW, Morton PA, Loh DY, Bluestone JA, Jenkins MK (August 1995). <a rel="nofollow" class="external text" href="https://doi.org/10.4049%2Fjimmunol.155.3.1032">"Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4"</a>. <i>Journal of Immunology</i>. <b>155</b> (3): 1032–1036. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.4049%2Fjimmunol.155.3.1032">10.4049/jimmunol.155.3.1032</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/7543510">7543510</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:23874889">23874889</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Antigen-dependent+clonal+expansion+of+a+trace+population+of+antigen-specific+CD4%2B+T+cells+in+vivo+is+dependent+on+CD28+costimulation+and+inhibited+by+CTLA-4&rft.volume=155&rft.issue=3&rft.pages=1032-1036&rft.date=1995-08&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A23874889%23id-name%3DS2CID&rft_id=info%3Apmid%2F7543510&rft_id=info%3Adoi%2F10.4049%2Fjimmunol.155.3.1032&rft.aulast=Kearney&rft.aufirst=ER&rft.au=Walunas%2C+TL&rft.au=Karr%2C+RW&rft.au=Morton%2C+PA&rft.au=Loh%2C+DY&rft.au=Bluestone%2C+JA&rft.au=Jenkins%2C+MK&rft_id=https%3A%2F%2Fdoi.org%2F10.4049%252Fjimmunol.155.3.1032&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" class="Z3988"></span></span> </li> <li id="cite_note-81"><span class="mw-cite-backlink"><b><a href="#cite_ref-81">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLinsleyGreeneTanBradshaw1992" class="citation journal cs1">Linsley PS, Greene JL, Tan P, Bradshaw J, Ledbetter JA, Anasetti C, Damle NK (December 1992). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119471">"Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes"</a>. <i>The Journal of Experimental Medicine</i>. <b>176</b> (6): 1595–1604. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1084%2Fjem.176.6.1595">10.1084/jem.176.6.1595</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119471">2119471</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/1334116">1334116</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+Experimental+Medicine&rft.atitle=Coexpression+and+functional+cooperation+of+CTLA-4+and+CD28+on+activated+T+lymphocytes&rft.volume=176&rft.issue=6&rft.pages=1595-1604&rft.date=1992-12&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2119471%23id-name%3DPMC&rft_id=info%3Apmid%2F1334116&rft_id=info%3Adoi%2F10.1084%2Fjem.176.6.1595&rft.aulast=Linsley&rft.aufirst=PS&rft.au=Greene%2C+JL&rft.au=Tan%2C+P&rft.au=Bradshaw%2C+J&rft.au=Ledbetter%2C+JA&rft.au=Anasetti%2C+C&rft.au=Damle%2C+NK&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2119471&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" class="Z3988"></span></span> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Ipilimumab&action=edit&section=16" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.cancer.gov/publications/dictionaries/cancer-drug/def/ipilimumab">"Ipilimumab"</a>. <i>NCI Drug Dictionary</i>. National Cancer Institute.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=NCI+Drug+Dictionary&rft.atitle=Ipilimumab&rft_id=https%3A%2F%2Fwww.cancer.gov%2Fpublications%2Fdictionaries%2Fcancer-drug%2Fdef%2Fipilimumab&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.cancer.gov/about-cancer/treatment/drugs/ipilimumab">"Ipilimumab"</a>. <i>National Cancer Institute</i>. 21 April 2011.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=National+Cancer+Institute&rft.atitle=Ipilimumab&rft.date=2011-04-21&rft_id=https%3A%2F%2Fwww.cancer.gov%2Fabout-cancer%2Ftreatment%2Fdrugs%2Fipilimumab&rfr_id=info%3Asid%2Fen.wikipedia.org%3AIpilimumab" 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style="font-size:114%;margin:0 4em"><a href="/wiki/Targeted_cancer_therapy" class="mw-redirect" title="Targeted cancer therapy">Targeted cancer therapy</a> / <a href="/wiki/Antineoplastic" class="mw-redirect" title="Antineoplastic">antineoplastic agents</a> (<a href="/wiki/ATC_code_L01" title="ATC code L01">L01</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cancer_immunotherapy" title="Cancer immunotherapy">CI</a> <a href="/wiki/Monoclonal_antibody_therapy" title="Monoclonal antibody therapy">monoclonal antibodies</a> ("-mab")</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">Receptor tyrosine kinase</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/ErbB" title="ErbB">ErbB</a>: <i><a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">HER1/EGFR</a></i> (<a href="/wiki/Cetuximab" title="Cetuximab">Cetuximab</a></li> <li><a href="/wiki/Panitumumab" title="Panitumumab">Panitumumab</a>)</li> <li><i><a href="/wiki/HER2/neu" class="mw-redirect" title="HER2/neu">HER2/neu</a></i> (<a href="/wiki/Pertuzumab" title="Pertuzumab">Pertuzumab</a></li> <li><a href="/wiki/Trastuzumab" title="Trastuzumab">Trastuzumab</a> (<a href="/wiki/Trastuzumab/hyaluronidase" title="Trastuzumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Trastuzumab_emtansine" title="Trastuzumab emtansine">Trastuzumab emtansine</a></li> <li><a href="/wiki/Trastuzumab_deruxtecan" title="Trastuzumab deruxtecan">Trastuzumab deruxtecan</a></li> <li><a href="/wiki/Zanidatamab" title="Zanidatamab">Zanidatamab</a> )</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Others for solid tumors</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/EpCAM" class="mw-redirect" title="EpCAM">EpCAM</a></i> (<a href="/wiki/Catumaxomab" title="Catumaxomab">Catumaxomab</a></li> <li><a href="/wiki/Edrecolomab" title="Edrecolomab">Edrecolomab</a>)</li> <li><i><a href="/wiki/Vascular_endothelial_growth_factor_A" title="Vascular endothelial growth factor A">VEGF-A</a></i> (<a href="/wiki/Bevacizumab" title="Bevacizumab">Bevacizumab</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Leukemia" title="Leukemia">Leukemia</a>/<a href="/wiki/Lymphoma" title="Lymphoma">lymphoma</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Lymphatic_system" title="Lymphatic system">lymphoid</a>: <i><a href="/wiki/CD3_(immunology)" title="CD3 (immunology)">CD3</a></i> (<a href="/wiki/Glofitamab" title="Glofitamab">Glofitamab</a>, <a href="/wiki/Elranatamab" title="Elranatamab">Elranatamab</a>, <a href="/wiki/Mosunetuzumab" title="Mosunetuzumab">Mosunetuzumab</a>), <i><a href="/wiki/CD20" title="CD20">CD20</a></i> (<a href="/wiki/Glofitamab" title="Glofitamab">Glofitamab</a></li> <li><a href="/wiki/Ibritumomab_tiuxetan" title="Ibritumomab tiuxetan">Ibritumomab</a></li> <li><a href="/wiki/Mosunetuzumab" title="Mosunetuzumab">Mosunetuzumab</a></li> <li><a href="/wiki/Obinutuzumab" title="Obinutuzumab">Obinutuzumab</a></li> <li><a href="/wiki/Ofatumumab" title="Ofatumumab">Ofatumumab</a></li> <li><a href="/wiki/Rituximab" title="Rituximab">Rituximab</a></li> <li><a href="/wiki/Tositumomab" title="Tositumomab">Tositumomab</a>), <i><a href="/wiki/CD30" title="CD30">CD30</a></i> (<a href="/wiki/Brentuximab_vedotin" title="Brentuximab vedotin">Brentuximab</a>), <i><a href="/wiki/CD52" title="CD52">CD52</a></i> (<a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a>)</li></ul> <ul><li><a href="/wiki/Myeloid" class="mw-redirect" title="Myeloid">myeloid</a>: <i><a href="/wiki/CD33" title="CD33">CD33</a></i> (<a href="/wiki/Gemtuzumab_ozogamicin" title="Gemtuzumab ozogamicin">Gemtuzumab ozogamicin</a>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amivantamab" title="Amivantamab">Amivantamab</a></li> <li><a href="/wiki/Atezolizumab" title="Atezolizumab">Atezolizumab</a> (<a href="/wiki/Atezolizumab/hyaluronidase" title="Atezolizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Avelumab" title="Avelumab">Avelumab</a></li> <li><a href="/wiki/Axatilimab" title="Axatilimab">Axatilimab</a></li> <li><a href="/wiki/Belantamab_mafodotin" title="Belantamab mafodotin">Belantamab mafodotin</a></li> <li><a href="/wiki/Bermekimab" title="Bermekimab">Bermekimab</a></li> <li><a href="/wiki/Blinatumomab" title="Blinatumomab">Blinatumomab</a></li> <li><a href="/wiki/Cemiplimab" title="Cemiplimab">Cemiplimab</a></li> <li><a href="/wiki/Daratumumab" title="Daratumumab">Daratumumab</a></li> <li><a href="/wiki/Dinutuximab_beta" class="mw-redirect" title="Dinutuximab beta">Dinutuximab beta</a></li> <li><a href="/wiki/Dostarlimab" title="Dostarlimab">Dostarlimab</a></li> <li><a href="/wiki/Durvalumab" title="Durvalumab">Durvalumab</a></li> <li><a href="/wiki/Elotuzumab" title="Elotuzumab">Elotuzumab</a></li> <li><a href="/wiki/Enfortumab_vedotin" title="Enfortumab vedotin">Enfortumab vedotin</a></li> <li><a href="/wiki/Epcoritamab" title="Epcoritamab">Epcoritamab</a></li> <li><a href="/wiki/Inotuzumab_ozogamicin" title="Inotuzumab ozogamicin">Inotuzumab ozogamicin</a></li> <li><a class="mw-selflink selflink">Ipilimumab</a></li> <li><a href="/wiki/Isatuximab" title="Isatuximab">Isatuximab</a></li> <li><a href="/wiki/Loncastuximab_tesirine" title="Loncastuximab tesirine">Loncastuximab tesirine</a></li> <li><a href="/wiki/Mirvetuximab_soravtansine" title="Mirvetuximab soravtansine">Mirvetuximab soravtansine</a></li> <li><a href="/wiki/Mogamulizumab" title="Mogamulizumab">Mogamulizumab</a></li> <li><a href="/wiki/Moxetumomab_pasudotox" title="Moxetumomab pasudotox">Moxetumomab pasudotox</a></li> <li><a href="/wiki/Naxitamab" title="Naxitamab">Naxitamab</a></li> <li><a href="/wiki/Necitumumab" title="Necitumumab">Necitumumab</a></li> <li><a href="/wiki/Nivolumab" title="Nivolumab">Nivolumab</a></li> <li><a href="/wiki/Olaratumab" title="Olaratumab">Olaratumab</a></li> <li><a href="/wiki/Oportuzumab_monatox" title="Oportuzumab monatox">Oportuzumab monatox</a></li> <li><a href="/wiki/Pembrolizumab" title="Pembrolizumab">Pembrolizumab</a></li> <li><a href="/wiki/Polatuzumab_vedotin" title="Polatuzumab vedotin">Polatuzumab vedotin</a></li> <li><a href="/w/index.php?title=Prolgolimab&action=edit&redlink=1" class="new" title="Prolgolimab (page does not exist)">Prolgolimab</a></li> <li><a href="/wiki/Ramucirumab" title="Ramucirumab">Ramucirumab</a></li> <li><a href="/wiki/Retifanlimab" title="Retifanlimab">Retifanlimab</a></li> <li><a href="/w/index.php?title=Sabatolimab&action=edit&redlink=1" class="new" title="Sabatolimab (page does not exist)">Sabatolimab</a></li> <li><a href="/wiki/Sacituzumab_govitecan" title="Sacituzumab govitecan">Sacituzumab govitecan</a></li> <li><a href="/wiki/Serplulimab" title="Serplulimab">Serplulimab</a></li> <li><a href="/wiki/Sugemalimab" title="Sugemalimab">Sugemalimab</a></li> <li><a href="/wiki/Tafasitamab" title="Tafasitamab">Tafasitamab</a></li> <li><a href="/wiki/Talquetamab" title="Talquetamab">Talquetamab</a></li> <li><a href="/wiki/Tarlatamab" title="Tarlatamab">Tarlatamab</a></li> <li><a href="/wiki/Teclistamab" title="Teclistamab">Teclistamab</a></li> <li><a href="/wiki/Tislelizumab" title="Tislelizumab">Tislelizumab</a></li> <li><a href="/wiki/Tisotumab_vedotin" title="Tisotumab vedotin">Tisotumab vedotin</a></li> <li><a href="/wiki/Toripalimab" title="Toripalimab">Toripalimab</a></li> <li><a href="/wiki/Tremelimumab" title="Tremelimumab">Tremelimumab</a></li> <li><a href="/wiki/Zolbetuximab" title="Zolbetuximab">Zolbetuximab</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Tyrosine_kinase_inhibitor" title="Tyrosine kinase inhibitor">Tyrosine kinase inhibitors</a> ("-nib")</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">Receptor tyrosine kinase</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/ErbB" title="ErbB">ErbB</a>: <i><a href="/wiki/Epidermal_growth_factor_receptor" title="Epidermal growth factor receptor">HER1/EGFR</a></i> (<a href="/wiki/Afatinib" title="Afatinib">Afatinib</a></li> <li><a href="/wiki/Aumolertinib" title="Aumolertinib">Aumolertinib</a></li> <li><a href="/wiki/Brigatinib" title="Brigatinib">Brigatinib</a></li> <li><a href="/wiki/Dacomitinib" title="Dacomitinib">Dacomitinib</a></li> <li><a href="/wiki/Erlotinib" title="Erlotinib">Erlotinib</a></li> <li><a href="/wiki/Gefitinib" title="Gefitinib">Gefitinib</a></li> <li><a href="/wiki/Icotinib" title="Icotinib">Icotinib</a></li> <li><a href="/wiki/Lazertinib" title="Lazertinib">Lazertinib</a></li> <li><a href="/wiki/Mobocertinib" title="Mobocertinib">Mobocertinib</a></li> <li><a href="/wiki/Olmutinib" title="Olmutinib">Olmutinib</a></li> <li><a href="/wiki/Osimertinib" title="Osimertinib">Osimertinib</a></li> <li><a href="/wiki/Rociletinib" title="Rociletinib">Rociletinib</a></li> <li><a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a>)</li></ul> <ul><li><i>HER1/EGFR and <a href="/wiki/HER2/neu" class="mw-redirect" title="HER2/neu">HER2/neu</a></i> <ul><li><a href="/wiki/Lapatinib" title="Lapatinib">Lapatinib</a></li> <li><a href="/wiki/Neratinib" title="Neratinib">Neratinib</a></li> <li><a href="/wiki/Tucatinib" title="Tucatinib">Tucatinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/BRAF_(gene)" title="BRAF (gene)">BRAF</a></i> <ul><li><a href="/wiki/Dabrafenib" title="Dabrafenib">Dabrafenib</a></li> <li><a href="/wiki/Encorafenib" title="Encorafenib">Encorafenib</a></li> <li><a href="/wiki/Vemurafenib" title="Vemurafenib">Vemurafenib</a></li></ul></li></ul> <ul><li><a href="/wiki/RTK_class_III" title="RTK class III">RTK class III</a>: <i><a href="/wiki/CD117" class="mw-redirect" title="CD117">C-kit</a> and <a href="/wiki/Platelet-derived_growth_factor_receptor" title="Platelet-derived growth factor receptor">PDGFR</a></i> (<a href="/wiki/Avapritinib" title="Avapritinib">Avapritinib</a></li> <li><a href="/wiki/Axitinib" title="Axitinib">Axitinib</a></li> <li><a href="/wiki/Masitinib" title="Masitinib">Masitinib</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Ripretinib" title="Ripretinib">Ripretinib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Toceranib" title="Toceranib">Toceranib</a>)</li> <li><i><a href="/wiki/CD135" title="CD135">FLT3</a></i> (<a href="/wiki/Lestaurtinib" title="Lestaurtinib">Lestaurtinib</a>, <a href="/wiki/Gilteritinib" title="Gilteritinib">Gilteritinib</a> (AXL, ALK, LTK))</li></ul> <ul><li><i><a href="/wiki/VEGF_receptors" class="mw-redirect" title="VEGF receptors">VEGFR</a></i> <ul><li><a href="/wiki/Axitinib" title="Axitinib">Axitinib</a></li> <li><a href="/wiki/Cediranib" title="Cediranib">Cediranib</a></li> <li><a href="/wiki/Fruquintinib" title="Fruquintinib">Fruquintinib</a></li> <li><a href="/wiki/Lenvatinib" title="Lenvatinib">Lenvatinib</a></li> <li><a href="/wiki/Nintedanib" title="Nintedanib">Nintedanib</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Regorafenib" title="Regorafenib">Regorafenib</a></li> <li><a href="/wiki/Semaxanib" title="Semaxanib">Semaxanib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Tivozanib" title="Tivozanib">Tivozanib</a></li> <li><a href="/wiki/Toceranib" title="Toceranib">Toceranib</a></li> <li><a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Anaplastic_lymphoma_kinase" title="Anaplastic lymphoma kinase">ALK</a></i> <ul><li><a href="/wiki/Alectinib" title="Alectinib">Alectinib</a></li> <li><a href="/wiki/Brigatinib" title="Brigatinib">Brigatinib</a></li> <li><a href="/wiki/Ceritinib" title="Ceritinib">Ceritinib</a></li> <li><a href="/wiki/Crizotinib" title="Crizotinib">Crizotinib</a></li> <li><a href="/wiki/Lorlatinib" title="Lorlatinib">Lorlatinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/RET_proto-oncogene" title="RET proto-oncogene">RET</a> inhibitors:</i> <a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a> (ALK, ROS1, NTRK), <a href="/wiki/Futibatinib" title="Futibatinib">Futibatinib</a> (FGFR2), <a href="/wiki/Infigratinib" title="Infigratinib">Infigratinib</a>, <a href="/wiki/Larotrectinib" title="Larotrectinib">Larotrectinib</a> (NTRK), <a href="/wiki/Pemigatinib" title="Pemigatinib">Pemigatinib</a> (FGFR), <a href="/wiki/Pralsetinib" title="Pralsetinib">Pralsetinib</a>, <a href="/wiki/Repotrectinib" title="Repotrectinib">Repotrectinib</a> (ROS1, TRK, ALK), <a href="/wiki/Selpercatinib" title="Selpercatinib">Selpercatinib</a> (VEGFR, FGFR), <a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a> (VEGFR, EGFR).</li></ul> <ul><li><i><a href="/wiki/C-Met" class="mw-redirect" title="C-Met">c-MET</a> inhibitors:</i> <a href="/wiki/Cabozantinib" title="Cabozantinib">Cabozantinib</a> (VEGFR), <a href="/wiki/Capmatinib" title="Capmatinib">Capmatinib</a>, <a href="/wiki/Crizotinib" title="Crizotinib">Crizotinib</a> (ALK)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Non-receptor_tyrosine_kinase" title="Non-receptor tyrosine kinase">Non-receptor</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Bcr-abl_fusion_protein" class="mw-redirect" title="Bcr-abl fusion protein">bcr-abl</a></i> <ul><li><a href="/wiki/Asciminib" title="Asciminib">Asciminib</a></li> <li><a href="/wiki/Bosutinib" title="Bosutinib">Bosutinib</a></li> <li><a href="/wiki/Dasatinib" title="Dasatinib">Dasatinib</a></li> <li><a href="/wiki/Imatinib" title="Imatinib">Imatinib</a></li> <li><a href="/wiki/Nilotinib" title="Nilotinib">Nilotinib</a></li> <li><a href="/wiki/Ponatinib" title="Ponatinib">Ponatinib</a></li> <li><a href="/wiki/Radotinib" title="Radotinib">Radotinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Src_(gene)" class="mw-redirect" title="Src (gene)">Src</a></i> (<a href="/wiki/Bosutinib" title="Bosutinib">Bosutinib</a></li> <li><a href="/wiki/Dasatinib" title="Dasatinib">Dasatinib</a>)</li></ul> <ul><li><i><a href="/wiki/Janus_kinase" title="Janus kinase">Janus kinase</a> (JAK)</i> <ul><li><a href="/wiki/Baricitinib" title="Baricitinib">Baricitinib</a></li> <li><a href="/wiki/Fedratinib" title="Fedratinib">Fedratinib</a></li> <li><a href="/wiki/Filgotinib" title="Filgotinib">Filgotinib</a></li> <li><a href="/wiki/Lestaurtinib" title="Lestaurtinib">Lestaurtinib</a></li> <li><a href="/wiki/Momelotinib" title="Momelotinib">Momelotinib</a></li> <li><a href="/wiki/Pacritinib" title="Pacritinib">Pacritinib</a></li> <li><a href="/wiki/Ruxolitinib" title="Ruxolitinib">Ruxolitinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Mitogen-activated_protein_kinase_kinase" title="Mitogen-activated protein kinase kinase">MAP2K</a> (MEK)</i> <ul><li><a href="/wiki/Binimetinib" title="Binimetinib">Binimetinib</a></li> <li><a href="/wiki/Cobimetinib" title="Cobimetinib">Cobimetinib</a></li> <li><a href="/wiki/Selumetinib" title="Selumetinib">Selumetinib</a></li> <li><a href="/wiki/Trametinib" title="Trametinib">Trametinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/EML4" title="EML4">EML4</a>-<a href="/wiki/Anaplastic_lymphoma_kinase" title="Anaplastic lymphoma kinase">ALK</a></i> <ul><li><a href="/wiki/Crizotinib" title="Crizotinib">Crizotinib</a></li> <li><a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a></li> <li><a href="/wiki/Lorlatinib" title="Lorlatinib">Lorlatinib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Bruton%27s_tyrosine_kinase" title="Bruton's tyrosine kinase">Bruton's</a> (BTK)</i> <ul><li><a href="/wiki/Acalabrutinib" title="Acalabrutinib">Acalabrutinib</a></li> <li><a href="/wiki/Ibrutinib" title="Ibrutinib">Ibrutinib</a></li> <li><a href="/wiki/Orelabrutinib" title="Orelabrutinib">Orelabrutinib</a></li> <li><a href="/wiki/Pirtobrutinib" title="Pirtobrutinib">Pirtobrutinib</a></li> <li><a href="/wiki/Zanubrutinib" title="Zanubrutinib">Zanubrutinib</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Fusion_protein" title="Fusion protein">fusion protein</a> against <a href="/wiki/Vascular_endothelial_growth_factor" title="Vascular endothelial growth factor">VEGF</a></i> (<a href="/wiki/Aflibercept" title="Aflibercept">Aflibercept</a>)</li></ul> <ul><li><i><a href="/wiki/Proapoptotic" class="mw-redirect" title="Proapoptotic">proapoptotic</a> peptide against <a href="/wiki/ANXA2" class="mw-redirect" title="ANXA2">ANXA2</a> and <a href="/wiki/Prohibitin" title="Prohibitin">prohibitin</a></i> (<a href="/wiki/Adipotide" class="mw-redirect" title="Adipotide">Adipotide</a>)</li></ul> <ul><li><i><a href="/wiki/Exotoxin" title="Exotoxin">exotoxin</a> against <a href="/wiki/Interleukin_2" title="Interleukin 2">IL-2</a></i> (<a href="/wiki/Denileukin_diftitox" title="Denileukin diftitox">Denileukin diftitox</a>)</li></ul> <ul><li><i><a href="/wiki/MTOR_inhibitor" class="mw-redirect" title="MTOR inhibitor">mTOR inhibitors</a></i> <ul><li><a href="/wiki/Everolimus" title="Everolimus">Everolimus</a></li> <li><a href="/wiki/Ridaforolimus" title="Ridaforolimus">Ridaforolimus</a></li> <li><a href="/wiki/Sirolimus" title="Sirolimus">Sirolimus</a></li> <li><a href="/wiki/Temsirolimus" title="Temsirolimus">Temsirolimus</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Hedgehog_signaling_pathway" title="Hedgehog signaling pathway">hedgehog</a> inhibitors</i> <ul><li><a href="/wiki/Glasdegib" title="Glasdegib">Glasdegib</a></li> <li><a href="/wiki/Sonidegib" title="Sonidegib">Sonidegib</a></li> <li><a href="/wiki/Vismodegib" title="Vismodegib">Vismodegib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/CDK_inhibitor" title="CDK inhibitor">CDK inhibitors</a></i> <ul><li><a href="/wiki/Abemaciclib" title="Abemaciclib">Abemaciclib</a></li> <li><a href="/wiki/Dalpiciclib" title="Dalpiciclib">Dalpiciclib</a></li> <li><a href="/wiki/Palbociclib" title="Palbociclib">Palbociclib</a></li> <li><a href="/wiki/Ribociclib" title="Ribociclib">Ribociclib</a></li> <li><a href="/wiki/Trilaciclib" title="Trilaciclib">Trilaciclib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/KRAS" title="KRAS">KRAS</a> inhibitors</i> <ul><li><a href="/wiki/Adagrasib" title="Adagrasib">Adagrasib</a></li> <li><a href="/wiki/Sotorasib" title="Sotorasib">Sotorasib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Pi3K_inhibitor" class="mw-redirect" title="Pi3K inhibitor">Pi3K inhibitors</a></i> <ul><li><a href="/wiki/Alpelisib" title="Alpelisib">Alpelisib</a></li> <li><a href="/wiki/Copanlisib" title="Copanlisib">Copanlisib</a></li> <li><a href="/wiki/Duvelisib" title="Duvelisib">Duvelisib</a></li> <li><a href="/wiki/Idelalisib" title="Idelalisib">Idelalisib</a></li> <li><a href="/wiki/Inavolisib" title="Inavolisib">Inavolisib</a></li> <li><a href="/wiki/Parsaclisib" title="Parsaclisib">Parsaclisib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/MEN1" title="MEN1">Menin</a> inhibitors</i> <ul><li><a href="/wiki/Revumenib" title="Revumenib">Revumenib</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Fibroblast_growth_factor_receptor" title="Fibroblast growth factor receptor">Fibroblast growth factor receptor</a></i> (FGFR) inhibitors</li> <li><a href="/wiki/Erdafitinib" title="Erdafitinib">Erdafitinib</a></li> <li><a href="/wiki/Futibatinib" title="Futibatinib">Futibatinib</a></li> <li><a href="/wiki/Infigratinib" title="Infigratinib">Infigratinib</a></li> <li><a href="/wiki/Pemigatinib" title="Pemigatinib">Pemigatinib</a></li></ul> <ul><li><a href="/wiki/Cabozantinib" title="Cabozantinib">Cabozantinib</a></li> <li><a href="/wiki/Capmatinib" title="Capmatinib">Capmatinib</a></li> <li><a href="/wiki/Entrectinib" title="Entrectinib">Entrectinib</a></li> <li><a href="/wiki/Gilteritinib" title="Gilteritinib">Gilteritinib</a></li> <li><a href="/wiki/Larotrectinib" title="Larotrectinib">Larotrectinib</a></li> <li><a href="/wiki/Lenvatinib" title="Lenvatinib">Lenvatinib</a></li> <li><a href="/wiki/Masitinib" title="Masitinib">Masitinib</a></li> <li><a href="/wiki/Midostaurin" title="Midostaurin">Midostaurin</a></li> <li><a href="/wiki/Nintedanib" title="Nintedanib">Nintedanib</a></li> <li><a href="/wiki/Odronextamab" title="Odronextamab">Odronextamab</a></li> <li><a href="/wiki/Pazopanib" title="Pazopanib">Pazopanib</a></li> <li><a href="/wiki/Pexidartinib" title="Pexidartinib">Pexidartinib</a></li> <li><a href="/wiki/Quizartinib" title="Quizartinib">Quizartinib</a></li> <li><a href="/wiki/Regorafenib" title="Regorafenib">Regorafenib</a></li> <li><a href="/wiki/Ripretinib" title="Ripretinib">Ripretinib</a></li> <li><a href="/wiki/Sorafenib" title="Sorafenib">Sorafenib</a></li> <li><a href="/wiki/Sunitinib" title="Sunitinib">Sunitinib</a></li> <li><a href="/wiki/Tebentafusp" title="Tebentafusp">Tebentafusp</a></li> <li><a href="/wiki/Tepotinib" title="Tepotinib">Tepotinib</a></li> <li><a href="/wiki/Vandetanib" title="Vandetanib">Vandetanib</a></li> <li><a href="/wiki/Venetoclax" title="Venetoclax">Venetoclax</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"></div><div role="navigation" class="navbox" aria-labelledby="Monoclonal_antibodies_for_tumors" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Monoclonals_for_tumors" title="Template:Monoclonals for tumors"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Monoclonals_for_tumors" title="Template talk:Monoclonals for tumors"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Monoclonals_for_tumors" title="Special:EditPage/Template:Monoclonals for tumors"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Monoclonal_antibodies_for_tumors" style="font-size:114%;margin:0 4em"><a href="/wiki/Monoclonal_antibody" title="Monoclonal antibody">Monoclonal antibodies</a> for tumors</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align: center;"><a href="/wiki/Neoplasm" title="Neoplasm">Tumor</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Human</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Adecatumumab" title="Adecatumumab">Adecatumumab</a><sup>§</sup></li> <li><a href="/wiki/Amivantamab" title="Amivantamab">Amivantamab</a></li> <li><a href="/wiki/Ascrinvacumab" title="Ascrinvacumab">Ascrinvacumab</a><sup>§</sup></li> <li><a href="/wiki/Atezolizumab" title="Atezolizumab">Atezolizumab</a> (<a href="/wiki/Atezolizumab/hyaluronidase" title="Atezolizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/w/index.php?title=Balstilimab&action=edit&redlink=1" class="new" title="Balstilimab (page does not exist)">Balstilimab</a><sup>†</sup></li> <li><a href="/w/index.php?title=Botensilimab&action=edit&redlink=1" class="new" title="Botensilimab (page does not exist)">Botensilimab</a></li> <li><a href="/wiki/Cixutumumab" title="Cixutumumab">Cixutumumab</a><sup>§</sup></li> <li><a href="/wiki/Conatumumab" title="Conatumumab">Conatumumab</a><sup>§</sup></li> <li><a href="/wiki/Daratumumab" title="Daratumumab">Daratumumab</a></li> <li><a href="/wiki/Drozitumab" title="Drozitumab">Drozitumab</a><sup>§</sup></li> <li><a href="/wiki/Duligotumab" class="mw-redirect" title="Duligotumab">Duligotumab</a><sup>§</sup></li> <li><a href="/wiki/Dusigitumab" title="Dusigitumab">Dusigitumab</a><sup>§</sup></li> <li><a href="/wiki/Enfortumab_vedotin" title="Enfortumab vedotin">Enfortumab vedotin</a></li> <li><a href="/wiki/Enoticumab" title="Enoticumab">Enoticumab</a><sup>§</sup></li> <li><a href="/wiki/Figitumumab" title="Figitumumab">Figitumumab</a><sup>§</sup></li> <li><a href="/wiki/Flanvotumab" title="Flanvotumab">Flanvotumab</a><sup>§</sup></li> <li><a href="/wiki/Ganitumab" title="Ganitumab">Ganitumab</a><sup>†</sup></li> <li><a href="/wiki/Glembatumumab_vedotin" title="Glembatumumab vedotin">Glembatumumab vedotin</a><sup>†</sup></li> <li><a href="/wiki/Intetumumab" title="Intetumumab">Intetumumab</a><sup>§</sup></li> <li><a class="mw-selflink selflink">Ipilimumab</a></li> <li><a href="/wiki/Iratumumab" title="Iratumumab">Iratumumab</a><sup>§</sup></li> <li><a href="/wiki/Istiratumab" title="Istiratumab">Istiratumab</a></li> <li><a href="/wiki/Icrucumab" title="Icrucumab">Icrucumab</a><sup>§</sup></li> <li><a href="/wiki/Lexatumumab" title="Lexatumumab">Lexatumumab</a><sup>§</sup></li> <li><a href="/wiki/Lucatumumab" title="Lucatumumab">Lucatumumab</a><sup>§</sup></li> <li><a href="/wiki/Mapatumumab" title="Mapatumumab">Mapatumumab</a><sup>§</sup></li> <li><a href="/wiki/Narnatumab" title="Narnatumab">Narnatumab</a><sup>§</sup></li> <li><a href="/wiki/Necitumumab" title="Necitumumab">Necitumumab</a></li> <li><a href="/wiki/Nesvacumab" title="Nesvacumab">Nesvacumab</a><sup>§</sup></li> <li><a href="/wiki/Nivolumab" title="Nivolumab">Nivolumab</a><sup>#</sup></li> <li><a href="/wiki/Ofatumumab" title="Ofatumumab">Ofatumumab</a></li> <li><a href="/wiki/Olaratumab" title="Olaratumab">Olaratumab</a><sup>†</sup></li> <li><a href="/wiki/Panitumumab" title="Panitumumab">Panitumumab</a></li> <li><a href="/wiki/Patritumab" title="Patritumab">Patritumab</a><sup>§</sup></li> <li><a href="/wiki/Pembrolizumab" title="Pembrolizumab">Pembrolizumab</a><sup>#</sup></li> <li><a href="/wiki/Pritumumab" title="Pritumumab">Pritumumab</a><sup>§</sup></li> <li><a href="/wiki/Radretumab" title="Radretumab">Radretumab</a><sup>§</sup></li> <li><a href="/wiki/Ramucirumab" title="Ramucirumab">Ramucirumab</a></li> <li><a href="/wiki/Rilotumumab" title="Rilotumumab">Rilotumumab</a><sup>†</sup></li> <li><a href="/wiki/Robatumumab" title="Robatumumab">Robatumumab</a><sup>§</sup></li> <li><a href="/wiki/Seribantumab" title="Seribantumab">Seribantumab</a><sup>§</sup></li> <li><a href="/wiki/Sugemalimab" title="Sugemalimab">Sugemalimab</a></li> <li><a href="/wiki/Tarextumab" title="Tarextumab">Tarextumab</a><sup>§</sup></li> <li><a href="/wiki/Tisotumab_vedotin" title="Tisotumab vedotin">Tisotumab vedotin</a></li> <li><a href="/wiki/Teprotumumab" title="Teprotumumab">Teprotumumab</a><sup>†</sup></li> <li><a href="/wiki/Tovetumab" title="Tovetumab">Tovetumab</a><sup>§</sup></li> <li><a href="/wiki/Vantictumab" title="Vantictumab">Vantictumab</a><sup>§</sup></li> <li><a href="/wiki/Technetium_(99mTc)_votumumab" title="Technetium (99mTc) votumumab">Votumumab</a><sup>§</sup></li> <li><a href="/wiki/Zalutumumab" title="Zalutumumab">Zalutumumab</a><sup>†</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Mouse</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Abagovomab" title="Abagovomab">Abagovomab</a></li> <li><a href="/wiki/Indium_(111In)_altumomab_pentetate" title="Indium (111In) altumomab pentetate">Altumomab pentetate</a></li> <li><a href="/wiki/Anatumomab_mafenatox" title="Anatumomab mafenatox">Anatumomab mafenatox</a></li> <li><a href="/wiki/Technetium_(99mTc)_arcitumomab" title="Technetium (99mTc) arcitumomab">Arcitumomab</a></li> <li><a href="/wiki/Bectumomab" title="Bectumomab">Bectumomab</a></li> <li><a href="/wiki/Blinatumomab" title="Blinatumomab">Blinatumomab</a></li> <li><a href="/wiki/Indium_(111In)_capromab_pendetide" title="Indium (111In) capromab pendetide">Capromab pendetide</a></li> <li><a href="/wiki/Detumomab" title="Detumomab">Detumomab</a></li> <li><a href="/wiki/Edrecolomab" title="Edrecolomab">Edrecolomab</a></li> <li><a href="/wiki/Ibritumomab_tiuxetan" title="Ibritumomab tiuxetan">Ibritumomab tiuxetan</a></li> <li><a href="/wiki/Indium_(111In)_igovomab" title="Indium (111In) igovomab">Igovomab</a></li> <li><a href="/wiki/Lilotomab" title="Lilotomab">Lilotomab</a></li> <li><a href="/wiki/Minretumomab" title="Minretumomab">Minretumomab</a></li> <li><a href="/wiki/Mitumomab" title="Mitumomab">Mitumomab</a></li> <li><a href="/wiki/Nacolomab_tafenatox" title="Nacolomab tafenatox">Nacolomab tafenatox</a></li> <li><a href="/wiki/Moxetumomab_pasudotox" title="Moxetumomab pasudotox">Moxetumomab pasudotox</a></li> <li><a href="/wiki/Naptumomab_estafenatox" title="Naptumomab estafenatox">Naptumomab estafenatox</a></li> <li><a href="/wiki/Oregovomab" title="Oregovomab">Oregovomab</a></li> <li><a href="/wiki/Pemtumomab" title="Pemtumomab">Pemtumomab</a><sup>†</sup></li> <li><a href="/wiki/Racotumomab" title="Racotumomab">Racotumomab</a></li> <li><a href="/wiki/Indium_(111In)_satumomab_pendetide" title="Indium (111In) satumomab pendetide">Satumomab pendetide</a></li> <li><a href="/wiki/Solitomab" title="Solitomab">Solitomab</a></li> <li><a href="/wiki/Taplitumomab_paptox" title="Taplitumomab paptox">Taplitumomab paptox</a></li> <li><a href="/wiki/Technetium_(99mTc)_nofetumomab_merpentan" title="Technetium (99mTc) nofetumomab merpentan">Nofetumomab merpentan</a></li> <li><a href="/wiki/Technetium_(99mTc)_pintumomab" title="Technetium (99mTc) pintumomab">Pintumomab</a></li> <li><a href="/wiki/Tenatumomab" title="Tenatumomab">Tenatumomab</a></li> <li><a href="/wiki/Tositumomab" title="Tositumomab">Tositumomab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Chimeric_antibody" class="mw-redirect" title="Chimeric antibody">Chimeric</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amatuximab" title="Amatuximab">Amatuximab</a><sup>§</sup></li> <li><a href="/wiki/Bavituximab" title="Bavituximab">Bavituximab</a><sup>§</sup></li> <li><a href="/wiki/Brentuximab_vedotin" title="Brentuximab vedotin">Brentuximab vedotin</a></li> <li><a href="/wiki/Carotuximab" title="Carotuximab">Carotuximab</a><sup>†</sup></li> <li><a href="/wiki/Cetuximab" title="Cetuximab">Cetuximab</a></li> <li><a href="/wiki/Iodine_(131_I)_derlotuximab_biotin" title="Iodine (131 I) derlotuximab biotin">Derlotuximab biotin</a><sup>§</sup></li> <li><a href="/wiki/Dinutuximab" title="Dinutuximab">Dinutuximab</a></li> <li><a href="/wiki/Ecromeximab" title="Ecromeximab">Ecromeximab</a><sup>§</sup></li> <li><a href="/wiki/Ensituximab" title="Ensituximab">Ensituximab</a><sup>§</sup></li> <li><a href="/wiki/Futuximab" title="Futuximab">Futuximab</a><sup>§</sup></li> <li><a href="/wiki/Girentuximab" title="Girentuximab">Girentuximab</a><sup>†</sup></li> <li><a href="/wiki/Indatuximab_ravtansine" title="Indatuximab ravtansine">Indatuximab ravtansine</a><sup>§</sup></li> <li><a href="/wiki/Isatuximab" title="Isatuximab">Isatuximab</a></li> <li><a href="/wiki/Loncastuximab_tesirine" title="Loncastuximab tesirine">Loncastuximab tesirine</a></li> <li><a href="/wiki/Margetuximab" title="Margetuximab">Margetuximab</a></li> <li><a href="/wiki/Mirvetuximab_soravtansine" title="Mirvetuximab soravtansine">Mirvetuximab soravtansine</a></li> <li><a href="/wiki/Rituximab" title="Rituximab">Rituximab</a><sup>#</sup></li> <li><a href="/wiki/Siltuximab" title="Siltuximab">Siltuximab</a></li> <li><a href="/wiki/Ublituximab" title="Ublituximab">Ublituximab</a></li> <li><a href="/wiki/Zolbetuximab" title="Zolbetuximab">Zolbetuximab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Humanized_antibody" title="Humanized antibody">Humanized</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Abituzumab" title="Abituzumab">Abituzumab</a><sup>§</sup></li> <li><a href="/wiki/Alemtuzumab" title="Alemtuzumab">Alemtuzumab</a></li> <li><a href="/wiki/Axatilimab" title="Axatilimab">Axatilimab</a></li> <li><a href="/wiki/Belantamab_mafodotin" title="Belantamab mafodotin">Belantamab mafodotin</a></li> <li><a href="/wiki/Bevacizumab" title="Bevacizumab">Bevacizumab</a></li> <li><a href="/wiki/Bivatuzumab_mertansine" title="Bivatuzumab mertansine">Bivatuzumab mertansine</a><sup>§</sup></li> <li><a href="/wiki/Brontictuzumab" title="Brontictuzumab">Brontictuzumab</a><sup>§</sup></li> <li><a href="/wiki/Cantuzumab_mertansine" title="Cantuzumab mertansine">Cantuzumab mertansine</a><sup>§</sup></li> <li><a href="/wiki/Cantuzumab_ravtansine" title="Cantuzumab ravtansine">Cantuzumab ravtansine</a><sup>§</sup></li> <li><a href="/wiki/Cirmtuzumab" title="Cirmtuzumab">Cirmtuzumab</a></li> <li><a href="/wiki/Citatuzumab_bogatox" title="Citatuzumab bogatox">Citatuzumab bogatox</a><sup>§</sup></li> <li><a href="/wiki/Yttrium_(90Y)_clivatuzumab_tetraxetan" title="Yttrium (90Y) clivatuzumab tetraxetan">Clivatuzumab tetraxetan</a></li> <li><a href="/wiki/Cofetuzumab_pelidotin" title="Cofetuzumab pelidotin">Cofetuzumab pelidotin</a></li> <li><a href="/wiki/Dacetuzumab" title="Dacetuzumab">Dacetuzumab</a><sup>§</sup></li> <li><a href="/wiki/Demcizumab" title="Demcizumab">Demcizumab</a><sup>§</sup></li> <li><a href="/wiki/Dalotuzumab" title="Dalotuzumab">Dalotuzumab</a><sup>§</sup></li> <li><a href="/wiki/Denintuzumab_mafodotin" title="Denintuzumab mafodotin">Denintuzumab mafodotin</a><sup>§</sup></li> <li><a href="/wiki/Elotuzumab" title="Elotuzumab">Elotuzumab</a></li> <li><a href="/wiki/Emactuzumab" title="Emactuzumab">Emactuzumab</a></li> <li><a href="/wiki/Emibetuzumab" title="Emibetuzumab">Emibetuzumab</a><sup>§</sup></li> <li><a href="/wiki/Enoblituzumab" title="Enoblituzumab">Enoblituzumab</a><sup>§</sup></li> <li><a href="/wiki/Epcoritamab" title="Epcoritamab">Epcoritamab</a></li> <li><a href="/wiki/Etaracizumab" title="Etaracizumab">Etaracizumab</a><sup>§</sup></li> <li><a href="/wiki/Farletuzumab" title="Farletuzumab">Farletuzumab</a><sup>§</sup></li> <li><a href="/wiki/Ficlatuzumab" title="Ficlatuzumab">Ficlatuzumab</a><sup>§</sup></li> <li><a href="/wiki/Flotetuzumab" title="Flotetuzumab">Flotetuzumab</a><sup>§</sup></li> <li><a href="/wiki/Gemtuzumab_ozogamicin" title="Gemtuzumab ozogamicin">Gemtuzumab ozogamicin</a></li> <li><a href="/wiki/Glofitamab" title="Glofitamab">Glofitamab</a></li> <li><a href="/wiki/Imgatuzumab" title="Imgatuzumab">Imgatuzumab</a><sup>§</sup></li> <li><a href="/wiki/Inotuzumab_ozogamicin" title="Inotuzumab ozogamicin">Inotuzumab ozogamicin</a></li> <li><a href="/wiki/Labetuzumab" title="Labetuzumab">Labetuzumab</a><sup>§</sup></li> <li><a href="/wiki/Lifastuzumab_vedotin" title="Lifastuzumab vedotin">Lifastuzumab vedotin</a><sup>§</sup></li> <li><a href="/wiki/Lintuzumab" title="Lintuzumab">Lintuzumab</a><sup>§</sup></li> <li><a href="/wiki/Lorvotuzumab_mertansine" title="Lorvotuzumab mertansine">Lorvotuzumab mertansine</a><sup>§</sup></li> <li><a href="/wiki/Lumretuzumab" title="Lumretuzumab">Lumretuzumab</a><sup>§</sup></li> <li><a href="/wiki/Matuzumab" title="Matuzumab">Matuzumab</a><sup>§</sup></li> <li><a href="/wiki/Milatuzumab" title="Milatuzumab">Milatuzumab</a><sup>§</sup></li> <li><a href="/wiki/Naxitamab" title="Naxitamab">Naxitamab</a></li> <li><a href="/wiki/Nimotuzumab" title="Nimotuzumab">Nimotuzumab</a><sup>†</sup></li> <li><a href="/wiki/Obinutuzumab" title="Obinutuzumab">Obinutuzumab</a></li> <li><a href="/wiki/Ocaratuzumab" title="Ocaratuzumab">Ocaratuzumab</a><sup>§</sup></li> <li><a href="/wiki/Odronextamab" title="Odronextamab">Odronextamab</a></li> <li><a href="/wiki/Otlertuzumab" title="Otlertuzumab">Otlertuzumab</a><sup>§</sup></li> <li><a href="/wiki/Onartuzumab" title="Onartuzumab">Onartuzumab</a><sup>§</sup></li> <li><a href="/wiki/Oportuzumab_monatox" title="Oportuzumab monatox">Oportuzumab monatox</a><sup>†</sup></li> <li><a href="/wiki/Parsatuzumab" title="Parsatuzumab">Parsatuzumab</a><sup>§</sup></li> <li><a href="/wiki/Pertuzumab" title="Pertuzumab">Pertuzumab</a></li> <li><a href="/wiki/Pinatuzumab_vedotin" title="Pinatuzumab vedotin">Pinatuzumab vedotin</a><sup>§</sup></li> <li><a href="/wiki/Polatuzumab_vedotin" title="Polatuzumab vedotin">Polatuzumab vedotin</a></li> <li><a href="/wiki/Rosmantuzumab" title="Rosmantuzumab">Rosmantuzumab</a></li> <li><a href="/wiki/Rovalpituzumab_tesirine" title="Rovalpituzumab tesirine">Rovalpituzumab tesirine</a><sup>†</sup></li> <li><a href="/wiki/Sacituzumab_govitecan" title="Sacituzumab govitecan">Sacituzumab govitecan</a></li> <li><a href="/wiki/Sibrotuzumab" title="Sibrotuzumab">Sibrotuzumab</a><sup>§</sup></li> <li><a href="/wiki/Simtuzumab" title="Simtuzumab">Simtuzumab</a><sup>§</sup></li> <li><a href="/wiki/Sofituzumab_vedotin" title="Sofituzumab vedotin">Sofituzumab vedotin</a><sup>§</sup></li> <li><a href="/wiki/Yttrium_(90Y)_tacatuzumab_tetraxetan" title="Yttrium (90Y) tacatuzumab tetraxetan">Tacatuzumab tetraxetan</a><sup>§</sup></li> <li><a href="/wiki/Tigatuzumab" title="Tigatuzumab">Tigatuzumab</a><sup>§</sup></li> <li><a href="/wiki/Trastuzumab" title="Trastuzumab">Trastuzumab</a><sup>#</sup> (<a href="/wiki/Trastuzumab_deruxtecan" title="Trastuzumab deruxtecan">+deruxtecan</a> / <a href="/wiki/Trastuzumab_emtansine" title="Trastuzumab emtansine">+emtansine</a>)</li> <li><a href="/wiki/Tucotuzumab_celmoleukin" title="Tucotuzumab celmoleukin">Tucotuzumab celmoleukin</a><sup>§</sup></li> <li><a href="/wiki/Vandortuzumab_vedotin" title="Vandortuzumab vedotin">Vandortuzumab vedotin</a><sup>§</sup></li> <li><a href="/wiki/Vanucizumab" title="Vanucizumab">Vanucizumab</a><sup>§</sup></li> <li><a href="/wiki/Veltuzumab" title="Veltuzumab">Veltuzumab</a><sup>§</sup></li> <li><a href="/wiki/Vorsetuzumab_mafodotin" title="Vorsetuzumab mafodotin">Vorsetuzumab mafodotin</a><sup>§</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Trifunctional_antibody" title="Trifunctional antibody">Rat/mouse hybrid</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Catumaxomab" title="Catumaxomab">Catumaxomab</a></li> <li><a href="/wiki/Ertumaxomab" title="Ertumaxomab">Ertumaxomab</a><sup>§</sup></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Chimeric + humanized</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Depatuxizumab_mafodotin" title="Depatuxizumab mafodotin">Depatuxizumab mafodotin</a><sup>†</sup></li> <li><a href="/wiki/Duvortuxizumab" title="Duvortuxizumab">Duvortuxizumab</a></li> <li><a href="/wiki/Ontuxizumab" title="Ontuxizumab">Ontuxizumab</a><sup>§</sup></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="background: transparent; padding: 0px;"><div><div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"></div><div role="navigation" class="navbox" aria-labelledby="Monoclonal_antibodies_for_the_immune_system" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2" style="text-align:center;"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Monoclonals_for_immune_system" title="Template:Monoclonals for immune system"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Monoclonals_for_immune_system" title="Template talk:Monoclonals for immune system"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Monoclonals_for_immune_system" title="Special:EditPage/Template:Monoclonals for immune system"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Monoclonal_antibodies_for_the_immune_system" style="font-size:114%;margin:0 4em"><a href="/wiki/Monoclonal_antibodies" class="mw-redirect" title="Monoclonal antibodies">Monoclonal antibodies</a> for the <a href="/wiki/Immune_system" title="Immune system">immune system</a></div></th></tr><tr><th scope="row" class="navbox-group" style="text-align:center;;width:1%"><a href="/wiki/Immune_system" title="Immune system">Immune system</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Human</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Immunosuppression" title="Immunosuppression">Immunosuppression</a></i>: <a href="/wiki/Abrilumab" title="Abrilumab">Abrilumab</a></li> <li><a href="/wiki/Adalimumab" title="Adalimumab">Adalimumab</a><sup>#</sup></li> <li><a href="/wiki/Anifrolumab" title="Anifrolumab">Anifrolumab</a></li> <li><a href="/wiki/Atorolimumab" title="Atorolimumab">Atorolimumab</a></li> <li><a href="/wiki/Avelumab" title="Avelumab">Avelumab</a></li> <li><a href="/w/index.php?title=Avdoralimab&action=edit&redlink=1" class="new" title="Avdoralimab (page does not exist)">Avdoralimab</a></li> <li><a href="/wiki/Belimumab" title="Belimumab">Belimumab</a></li> <li><a href="/wiki/Bleselumab" title="Bleselumab">Bleselumab</a></li> <li><a href="/wiki/Brodalumab" title="Brodalumab">Brodalumab</a></li> <li><a href="/wiki/Camidanlumab_tesirine" title="Camidanlumab tesirine">Camidanlumab tesirine</a></li> <li><a href="/wiki/Carlumab" title="Carlumab">Carlumab</a></li> <li><a href="/wiki/Cemiplimab" title="Cemiplimab">Cemiplimab</a></li> <li><a href="/wiki/Dupilumab" title="Dupilumab">Dupilumab</a></li> <li><a href="/wiki/Eldelumab" title="Eldelumab">Eldelumab</a></li> <li><a href="/wiki/Emapalumab" title="Emapalumab">Emapalumab</a></li> <li><a href="/wiki/Fresolimumab" title="Fresolimumab">Fresolimumab</a></li> <li><a href="/wiki/Golimumab" title="Golimumab">Golimumab</a></li> <li><a href="/wiki/Ianalumab" title="Ianalumab">Ianalumab</a><sup>†</sup></li> <li><a href="/wiki/Lanadelumab" title="Lanadelumab">Lanadelumab</a></li> <li><a href="/wiki/Lenzilumab" title="Lenzilumab">Lenzilumab</a></li> <li><a href="/wiki/Lerdelimumab" title="Lerdelimumab">Lerdelimumab</a></li> <li><a href="/wiki/Lirentelimab" title="Lirentelimab">Lirentelimab</a></li> <li><a href="/wiki/Lirilumab" title="Lirilumab">Lirilumab</a></li> <li><a href="/wiki/Mavrilimumab" title="Mavrilimumab">Mavrilimumab</a></li> <li><a href="/wiki/Metelimumab" title="Metelimumab">Metelimumab</a></li> <li><a href="/wiki/Morolimumab" title="Morolimumab">Morolimumab</a></li> <li><a href="/wiki/Namilumab" title="Namilumab">Namilumab</a></li> <li><a href="/wiki/Oleclumab" title="Oleclumab">Oleclumab</a></li> <li><a href="/wiki/Oxelumab" title="Oxelumab">Oxelumab</a>§</li> <li><a href="/wiki/Pamrevlumab" title="Pamrevlumab">Pamrevlumab</a></li> <li><a href="/wiki/Placulumab" title="Placulumab">Placulumab</a></li> <li><a href="/wiki/Relatlimab" title="Relatlimab">Relatlimab</a><sup>†</sup></li> <li><a href="/wiki/Sarilumab" title="Sarilumab">Sarilumab</a></li> <li><a href="/wiki/Sifalimumab" title="Sifalimumab">Sifalimumab</a></li> <li><a href="/wiki/Tabalumab" title="Tabalumab">Tabalumab</a></li> <li><a href="/wiki/Tezepelumab" title="Tezepelumab">Tezepelumab</a></li> <li><a href="/wiki/Ulocuplumab" title="Ulocuplumab">Ulocuplumab</a></li> <li><a href="/wiki/Varlilumab" title="Varlilumab">Varlilumab</a></li></ul> <ul><li><i>Immune activation</i>: <a class="mw-selflink selflink">Ipilimumab</a></li> <li><a href="/wiki/Durvalumab" title="Durvalumab">Durvalumab</a></li> <li><a href="/wiki/Nivolumab" title="Nivolumab">Nivolumab</a></li> <li><a href="/wiki/Tremelimumab" title="Tremelimumab">Tremelimumab</a></li> <li><a href="/wiki/Urelumab" title="Urelumab">Urelumab</a></li></ul> <ul><li><i>Other</i>: <a href="/wiki/Bertilimumab" title="Bertilimumab">Bertilimumab</a></li> <li><a href="/w/index.php?title=Ontamalimab&action=edit&redlink=1" class="new" title="Ontamalimab (page does not exist)">Ontamalimab</a></li> <li><a href="/wiki/Zanolimumab" title="Zanolimumab">Zanolimumab</a></li></ul> <ul><li><i>Combination</i>: <a href="/wiki/Nivolumab/relatlimab" title="Nivolumab/relatlimab">Nivolumab/relatlimab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Mouse</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Afelimomab" title="Afelimomab">Afelimomab</a></li> <li><a href="/wiki/Elsilimomab" title="Elsilimomab">Elsilimomab</a></li> <li><a href="/wiki/Faralimomab" title="Faralimomab">Faralimomab</a></li> <li><a href="/wiki/Gavilimomab" title="Gavilimomab">Gavilimomab</a></li> <li><a href="/wiki/Inolimomab" title="Inolimomab">Inolimomab</a></li> <li><a href="/wiki/Maslimomab" title="Maslimomab">Maslimomab</a></li> <li><a href="/wiki/Nerelimomab" title="Nerelimomab">Nerelimomab</a></li> <li><a href="/wiki/Odulimomab" title="Odulimomab">Odulimomab</a></li> <li><a href="/wiki/Telimomab_aritox" title="Telimomab aritox">Telimomab aritox</a></li> <li><a href="/wiki/Vepalimomab" title="Vepalimomab">Vepalimomab</a></li> <li><a href="/wiki/Zolimomab_aritox" title="Zolimomab aritox">Zolimomab aritox</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Chimeric_antibody" class="mw-redirect" title="Chimeric antibody">Chimeric</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Andecaliximab" title="Andecaliximab">Andecaliximab</a><sup>†</sup></li> <li><a href="/wiki/Basiliximab" title="Basiliximab">Basiliximab</a></li> <li><a href="/wiki/Clenoliximab" title="Clenoliximab">Clenoliximab</a></li> <li><a href="/wiki/Galiximab" title="Galiximab">Galiximab</a></li> <li><a href="/wiki/Gomiliximab" class="mw-redirect" title="Gomiliximab">Gomiliximab</a></li> <li><a href="/wiki/Infliximab" title="Infliximab">Infliximab</a></li> <li><a href="/wiki/Keliximab" title="Keliximab">Keliximab</a></li> <li><a href="/wiki/Lumiliximab" title="Lumiliximab">Lumiliximab</a></li> <li><a href="/wiki/Priliximab" title="Priliximab">Priliximab</a></li> <li><a href="/wiki/Teneliximab" title="Teneliximab">Teneliximab</a></li> <li><a href="/wiki/Vapaliximab" title="Vapaliximab">Vapaliximab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;"><a href="/wiki/Humanized_antibody" title="Humanized antibody">Humanized</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>Immunosuppressive:</i> <a href="/wiki/Apolizumab" title="Apolizumab">Apolizumab</a><sup>§</sup></li> <li><a href="/wiki/Aselizumab" title="Aselizumab">Aselizumab</a></li> <li><a href="/wiki/Atezolizumab" title="Atezolizumab">Atezolizumab</a></li> <li><a href="/wiki/Benralizumab" title="Benralizumab">Benralizumab</a></li> <li><a href="/wiki/Camrelizumab" title="Camrelizumab">Camrelizumab</a><sup>†</sup></li> <li><a href="/wiki/Cedelizumab" title="Cedelizumab">Cedelizumab</a></li> <li><a href="/wiki/Certolizumab_pegol" title="Certolizumab pegol">Certolizumab pegol</a></li> <li><a href="/wiki/Crizanlizumab" title="Crizanlizumab">Crizanlizumab</a></li> <li><a href="/wiki/Daclizumab" title="Daclizumab">Daclizumab</a></li> <li><a href="/wiki/Eculizumab" title="Eculizumab">Eculizumab</a></li> <li><a href="/wiki/Efalizumab" title="Efalizumab">Efalizumab</a><sup>‡</sup></li> <li><a href="/wiki/Epratuzumab" title="Epratuzumab">Epratuzumab</a></li> <li><a href="/wiki/Erlizumab" title="Erlizumab">Erlizumab</a></li> <li><a href="/wiki/Etrolizumab" title="Etrolizumab">Etrolizumab</a><sup>†</sup></li> <li><a href="/wiki/Fontolizumab" title="Fontolizumab">Fontolizumab</a></li> <li><a href="/wiki/Frexalimab" title="Frexalimab">Frexalimab</a><sup>†</sup></li> <li><a href="/wiki/Inebilizumab" title="Inebilizumab">Inebilizumab</a></li> <li><a href="/wiki/Itolizumab" title="Itolizumab">Itolizumab</a></li> <li><a href="/wiki/Lampalizumab" title="Lampalizumab">Lampalizumab</a><sup>†</sup></li> <li><a href="/wiki/Letolizumab" title="Letolizumab">Letolizumab</a></li> <li><a href="/wiki/Ligelizumab" title="Ligelizumab">Ligelizumab</a><sup>†</sup></li> <li><a href="/wiki/Lulizumab_pegol" title="Lulizumab pegol">Lulizumab pegol</a></li> <li><a href="/wiki/Mepolizumab" title="Mepolizumab">Mepolizumab</a></li> <li><a href="/wiki/Mogamulizumab" title="Mogamulizumab">Mogamulizumab</a></li> <li><a href="/wiki/Natalizumab" title="Natalizumab">Natalizumab</a></li> <li><a href="/wiki/Ocrelizumab" title="Ocrelizumab">Ocrelizumab</a> (<a href="/wiki/Ocrelizumab/hyaluronidase" title="Ocrelizumab/hyaluronidase">+hyaluronidase</a>)</li> <li><a href="/wiki/Omalizumab" title="Omalizumab">Omalizumab</a></li> <li><a href="/wiki/Ozoralizumab" title="Ozoralizumab">Ozoralizumab</a></li> <li><a href="/wiki/Pascolizumab" title="Pascolizumab">Pascolizumab</a></li> <li><a href="/wiki/Pateclizumab" title="Pateclizumab">Pateclizumab</a></li> <li><a href="/wiki/Pembrolizumab" title="Pembrolizumab">Pembrolizumab</a></li> <li><a href="/wiki/Pexelizumab" title="Pexelizumab">Pexelizumab</a></li> <li><a href="/wiki/Pidilizumab" title="Pidilizumab">Pidilizumab</a></li> <li><a href="/wiki/Plozalizumab" title="Plozalizumab">Plozalizumab</a></li> <li><a href="/wiki/PRO_140" class="mw-redirect" title="PRO 140">PRO 140</a><sup>†</sup></li> <li><a href="/wiki/Quilizumab" title="Quilizumab">Quilizumab</a></li> <li><a href="/wiki/Ravulizumab" title="Ravulizumab">Ravulizumab</a></li> <li><a href="/wiki/Reslizumab" title="Reslizumab">Reslizumab</a></li> <li><a href="/wiki/Retifanlimab" title="Retifanlimab">Retifanlimab</a></li> <li><a href="/wiki/Rontalizumab" title="Rontalizumab">Rontalizumab</a></li> <li><a href="/wiki/Rovelizumab" title="Rovelizumab">Rovelizumab</a></li> <li><a href="/wiki/Ruplizumab" title="Ruplizumab">Ruplizumab</a></li> <li><a href="/wiki/Samalizumab" title="Samalizumab">Samalizumab</a></li> <li><a href="/wiki/Satralizumab" title="Satralizumab">Satralizumab</a></li> <li><a href="/wiki/Siplizumab" title="Siplizumab">Siplizumab</a></li> <li><a href="/wiki/Spartalizumab" title="Spartalizumab">Spartalizumab</a><sup>†</sup></li> <li><a href="/wiki/Talizumab" title="Talizumab">Talizumab</a></li> <li><a href="/wiki/Teclistamab" title="Teclistamab">Teclistamab</a></li> <li><a href="/wiki/Teplizumab" title="Teplizumab">Teplizumab</a></li> <li><a href="/wiki/Tislelizumab" title="Tislelizumab">Tislelizumab</a></li> <li><a href="/wiki/Tocilizumab" title="Tocilizumab">Tocilizumab</a></li> <li><a href="/wiki/Toralizumab" title="Toralizumab">Toralizumab</a></li> <li><a href="/wiki/Tregalizumab" title="Tregalizumab">Tregalizumab</a></li> <li><a href="/wiki/Vatelizumab" title="Vatelizumab">Vatelizumab</a></li> <li><a href="/wiki/Vedolizumab" title="Vedolizumab">Vedolizumab</a></li> <li><a href="/wiki/Visilizumab" title="Visilizumab">Visilizumab</a></li> <li><a href="/wiki/Vobarilizumab" title="Vobarilizumab">Vobarilizumab</a></li> <li><a href="/wiki/TGN1412" class="mw-redirect" title="TGN1412">TGN1412</a><sup>§</sup><br /></li></ul> <p><i>Immune activation</i>: <a href="/wiki/Dostarlimab" title="Dostarlimab">Dostarlimab</a><br /> <i>Other:</i> <a href="/wiki/Ibalizumab" title="Ibalizumab">Ibalizumab</a> </p> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Chimeric + humanized<br /></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Otelixizumab" title="Otelixizumab">Otelixizumab</a></li> <li><a href="/wiki/Rozanolixizumab" title="Rozanolixizumab">Rozanolixizumab</a></li> <li><a href="/wiki/Sutimlimab" title="Sutimlimab">Sutimlimab</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="text-align:center;;width:1%"><a href="/wiki/Interleukin" title="Interleukin">Interleukin</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Human</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Bermekimab" title="Bermekimab">Bermekimab</a></li> <li><a href="/wiki/Brazikumab" title="Brazikumab">Brazikumab</a></li> <li><a href="/wiki/Briakinumab" title="Briakinumab">Briakinumab</a></li> <li><a href="/wiki/Canakinumab" title="Canakinumab">Canakinumab</a></li> <li><a href="/wiki/Fezakinumab" title="Fezakinumab">Fezakinumab</a></li> <li><a href="/wiki/Fletikumab" title="Fletikumab">Fletikumab</a></li> <li><a href="/wiki/Guselkumab" title="Guselkumab">Guselkumab</a></li> <li><a href="/wiki/Secukinumab" title="Secukinumab">Secukinumab</a></li> <li><a href="/wiki/Sirukumab" title="Sirukumab">Sirukumab</a></li> <li><a href="/wiki/Tralokinumab" title="Tralokinumab">Tralokinumab</a></li> <li><a href="/wiki/Ustekinumab" title="Ustekinumab">Ustekinumab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Humanized</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Anrukinzumab" title="Anrukinzumab">Anrukinzumab</a></li> <li><a href="/wiki/Bimekizumab" title="Bimekizumab">Bimekizumab</a></li> <li><a href="/wiki/Clazakizumab" title="Clazakizumab">Clazakizumab</a></li> <li><a href="/wiki/Gevokizumab" title="Gevokizumab">Gevokizumab</a></li> <li><a href="/wiki/Ixekizumab" title="Ixekizumab">Ixekizumab</a></li> <li><a href="/wiki/Mirikizumab" title="Mirikizumab">Mirikizumab</a><sup>†</sup></li> <li><a href="/wiki/Lebrikizumab" title="Lebrikizumab">Lebrikizumab</a></li> <li><a href="/wiki/Olokizumab" title="Olokizumab">Olokizumab</a><sup>†</sup></li> <li><a href="/wiki/Perakizumab" title="Perakizumab">Perakizumab</a></li> <li><a href="/wiki/Risankizumab" title="Risankizumab">Risankizumab</a></li> <li><a href="/wiki/Spesolimab" title="Spesolimab">Spesolimab</a></li> <li><a href="/wiki/Tildrakizumab" title="Tildrakizumab">Tildrakizumab</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%;text-align:center;">Veterinary</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Lokivetmab" title="Lokivetmab">Lokivetmab</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="text-align:center;;width:1%">Inflammatory <a href="/wiki/Lesion" title="Lesion">lesions</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Mouse" scope="row" class="navbox-group" style="width:1%;text-align:center;">Mouse</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Besilesomab" title="Besilesomab">Besilesomab</a></li> <li><a href="/wiki/Technetium_(99mTc)_fanolesomab" title="Technetium (99mTc) fanolesomab">Fanolesomab</a><sup>‡</sup></li> <li><a href="/wiki/Lemalesomab" title="Lemalesomab">Lemalesomab</a></li> <li><a href="/wiki/Technetium_(99mTc)_sulesomab" title="Technetium (99mTc) sulesomab">Sulesomab</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="text-align:center;;background: transparent; padding: 0px;"><div><div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> </div></div></td></tr></tbody></table></div> <style data-mw-deduplicate="TemplateStyles:r1130092004">.mw-parser-output .portal-bar{font-size:88%;font-weight:bold;display:flex;justify-content:center;align-items:baseline}.mw-parser-output .portal-bar-bordered{padding:0 2em;background-color:#fdfdfd;border:1px solid #a2a9b1;clear:both;margin:1em auto 0}.mw-parser-output .portal-bar-related{font-size:100%;justify-content:flex-start}.mw-parser-output .portal-bar-unbordered{padding:0 1.7em;margin-left:0}.mw-parser-output .portal-bar-header{margin:0 1em 0 0.5em;flex:0 0 auto;min-height:24px}.mw-parser-output .portal-bar-content{display:flex;flex-flow:row wrap;flex:0 1 auto;padding:0.15em 0;column-gap:1em;align-items:baseline;margin:0;list-style:none}.mw-parser-output .portal-bar-content-related{margin:0;list-style:none}.mw-parser-output .portal-bar-item{display:inline-block;margin:0.15em 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