Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer
The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies. An assay was developed and validated for the detection of antidrug antibodies (ADAs...
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| Veröffentlicht in: | Bioanalysis 2024, Vol.16 (21-22), p.1101-1113 |
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| creator | Zhu, Fengying Tu, Ya-Ping Sloss, Callum Wang, Yuemei |
| description | The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies.
An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.
Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.
Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials. |
| doi_str_mv | 10.1080/17576180.2024.2407228 |
| format | Article |
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An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.
Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.
Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.</description><identifier>ISSN: 1757-6180</identifier><identifier>EISSN: 1757-6199</identifier><identifier>DOI: 10.1080/17576180.2024.2407228</identifier><identifier>PMID: 39378056</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Antibodies, Monoclonal, Humanized - immunology ; Antibodies, Monoclonal, Humanized - therapeutic use ; Female ; Folate Receptor 1 - immunology ; Humans ; Immunoconjugates - immunology ; Maytansine - analogs & derivatives ; Maytansine - immunology ; Maytansine - therapeutic use ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - immunology</subject><ispartof>Bioanalysis, 2024, Vol.16 (21-22), p.1101-1113</ispartof><rights>2024 ImmunoGen, Inc. Published by Informa UK Limited, trading as Taylor & Francis Group 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2058-292c98900c8dfa4995c37f7f067f6adf0a5e5d0247905f11e3a1852f3eaeb0463</cites><orcidid>0009-0003-7423-2875</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583603/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583603/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39378056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Fengying</creatorcontrib><creatorcontrib>Tu, Ya-Ping</creatorcontrib><creatorcontrib>Sloss, Callum</creatorcontrib><creatorcontrib>Wang, Yuemei</creatorcontrib><title>Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer</title><title>Bioanalysis</title><addtitle>Bioanalysis</addtitle><description>The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies.
An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.
Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.
Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.</description><subject>Antibodies, Monoclonal, Humanized - immunology</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Female</subject><subject>Folate Receptor 1 - immunology</subject><subject>Humans</subject><subject>Immunoconjugates - immunology</subject><subject>Maytansine - analogs & derivatives</subject><subject>Maytansine - immunology</subject><subject>Maytansine - therapeutic use</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - immunology</subject><issn>1757-6180</issn><issn>1757-6199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUcFuFDEMjRCIVqWfAMoPzOIkk5nkhKoKClIlLnCOvFmnG7STjJLsQP-eWbVdgS-2bL1n-z3G3gvYCDDwUYx6HISBjQTZb2QPo5TmFbs89btBWPv6XBu4YNe1_oI1lDS2t2_ZhbJqNKCHS3a8qZVqnSg1ngOfYlmoHf_ECbe85oJLw1RjIh6n6ZjyA6XoY3vkMfEZW1xhlf-Obc9DPmAjXsjT3HLheJj32M25xhYX4nnBEjFxj8lTecfeBDxUun7OV-znl88_br9299_vvt3e3HdegjadtNJbYwG82QXsrdVejWEMMIxhwF0A1KR3qwSjBR2EIIXCaBkUIW2hH9QV-_TEOx-3E-38em7Bg5vL-l95dBmj-3-S4t495MUJoY0aQK0M-onBl1xroXAGC3AnL9yLF-7khXv2YsV9-HfzGfWivPoLRRmJBQ</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Zhu, Fengying</creator><creator>Tu, Ya-Ping</creator><creator>Sloss, Callum</creator><creator>Wang, Yuemei</creator><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0009-0003-7423-2875</orcidid></search><sort><creationdate>2024</creationdate><title>Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer</title><author>Zhu, Fengying ; Tu, Ya-Ping ; Sloss, Callum ; Wang, Yuemei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2058-292c98900c8dfa4995c37f7f067f6adf0a5e5d0247905f11e3a1852f3eaeb0463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antibodies, Monoclonal, Humanized - immunology</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Female</topic><topic>Folate Receptor 1 - immunology</topic><topic>Humans</topic><topic>Immunoconjugates - immunology</topic><topic>Maytansine - analogs & derivatives</topic><topic>Maytansine - immunology</topic><topic>Maytansine - therapeutic use</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Fengying</creatorcontrib><creatorcontrib>Tu, Ya-Ping</creatorcontrib><creatorcontrib>Sloss, Callum</creatorcontrib><creatorcontrib>Wang, Yuemei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioanalysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Fengying</au><au>Tu, Ya-Ping</au><au>Sloss, Callum</au><au>Wang, Yuemei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer</atitle><jtitle>Bioanalysis</jtitle><addtitle>Bioanalysis</addtitle><date>2024</date><risdate>2024</risdate><volume>16</volume><issue>21-22</issue><spage>1101</spage><epage>1113</epage><pages>1101-1113</pages><issn>1757-6180</issn><eissn>1757-6199</eissn><abstract>The aim of this research was to evaluate the immunogenicity of mirvetuximab soravtansine (MIRV), an antibody-drug conjugate in patients with folate receptor alpha-positive ovarian cancer across four clinical studies.
An assay was developed and validated for the detection of antidrug antibodies (ADAs) against MIRV. A cell-based method was also developed and validated for the detection of neutralizing anti-MIRV antibodies (NAbs). Both ADAs and NAbs were assessed across four clinical studies in 734 patients.
Across studies, MIRV demonstrated low immunogenicity with 7.8% of patients with treatment-emergent ADAs, 7.2% with treatment-unaffected ADAs, and 0.5% with treatment-enhanced ADAs. MIRV trough concentrations were comparable in ADA-negative and ADA-positive individuals. Limited data suggest that MIRV ADAs may be associated with decreased efficacy. Due to the very limited number of NAb-positive individuals, no conclusions could be drawn on the effect of NAb on efficacy.
Both the validation tests and the data from the MIRV clinical studies demonstrated that these assays were suitable and reliable for the detection of MIRV ADAs and NAbs. These validated assays will continue to be used to monitor MIRV immunogenicity in future clinical trials.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>39378056</pmid><doi>10.1080/17576180.2024.2407228</doi><tpages>13</tpages><orcidid>https://orcid.org/0009-0003-7423-2875</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; PubMed Central |
| subjects | Antibodies, Monoclonal, Humanized - immunology Antibodies, Monoclonal, Humanized - therapeutic use Female Folate Receptor 1 - immunology Humans Immunoconjugates - immunology Maytansine - analogs & derivatives Maytansine - immunology Maytansine - therapeutic use Ovarian Neoplasms - drug therapy Ovarian Neoplasms - immunology |
| title | Assessment of mirvetuximab soravtansine immunogenicity in patients with folate receptor alpha-positive ovarian cancer |
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