A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN -inactivating mutations
PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effecti...
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| Veröffentlicht in: | Future oncology (London, England) England), 2022-09, Vol.18 (30), p.3377-3387 |
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| creator | Rodón, Jordi Funchain, Pauline Laetsch, Theodore W Arkenau, Hendrik-Tobias Hervieu, Alice Singer, Christian F Murciano-Goroff, Yonina R Chawla, Sant P Anthony, Kristin Yamamiya, Ikuo Liu, Mei Halim, Abdel-Baset Benhadji, Karim A Takahashi, Osamu Delaloge, Suzette |
| description | PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the
gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline
mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline
-inactivating mutations. |
| doi_str_mv | 10.2217/fon-2022-0305 |
| format | Article |
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gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline
mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline
-inactivating mutations.</description><identifier>ISSN: 1479-6694</identifier><identifier>ISSN: 1744-8301</identifier><identifier>EISSN: 1744-8301</identifier><identifier>DOI: 10.2217/fon-2022-0305</identifier><identifier>PMID: 36039910</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Clinical Trial Protocol ; Clinical Trials, Phase II as Topic ; Germ Cells - metabolism ; Germ-Line Mutation ; Hamartoma Syndrome, Multiple - genetics ; Humans ; Neoplasms - drug therapy ; Neoplasms - genetics ; Phosphatidylinositol 3-Kinases - genetics ; Proto-Oncogene Proteins c-akt - genetics ; PTEN Phosphohydrolase - genetics</subject><ispartof>Future oncology (London, England), 2022-09, Vol.18 (30), p.3377-3387</ispartof><rights>2022 The Authors 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c318t-430a389d5397ab026e8fd214c274ce42d6b4c1179649e3d011b11800e8ea6743</citedby><cites>FETCH-LOGICAL-c318t-430a389d5397ab026e8fd214c274ce42d6b4c1179649e3d011b11800e8ea6743</cites><orcidid>0000-0003-3268-346X ; 0000-0001-9027-2891 ; 0000-0001-6467-3632 ; 0000-0002-2015-1549 ; 0000-0002-8497-3138 ; 0000-0003-2106-9165 ; 0000-0002-7568-8626 ; 0000-0001-9883-6970 ; 0000-0003-1294-0027</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/PMC10334253/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334253/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36039910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodón, Jordi</creatorcontrib><creatorcontrib>Funchain, Pauline</creatorcontrib><creatorcontrib>Laetsch, Theodore W</creatorcontrib><creatorcontrib>Arkenau, Hendrik-Tobias</creatorcontrib><creatorcontrib>Hervieu, Alice</creatorcontrib><creatorcontrib>Singer, Christian F</creatorcontrib><creatorcontrib>Murciano-Goroff, Yonina R</creatorcontrib><creatorcontrib>Chawla, Sant P</creatorcontrib><creatorcontrib>Anthony, Kristin</creatorcontrib><creatorcontrib>Yamamiya, Ikuo</creatorcontrib><creatorcontrib>Liu, Mei</creatorcontrib><creatorcontrib>Halim, Abdel-Baset</creatorcontrib><creatorcontrib>Benhadji, Karim A</creatorcontrib><creatorcontrib>Takahashi, Osamu</creatorcontrib><creatorcontrib>Delaloge, Suzette</creatorcontrib><title>A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN -inactivating mutations</title><title>Future oncology (London, England)</title><addtitle>Future Oncol</addtitle><description>PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the
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mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline
-inactivating mutations.</description><subject>Clinical Trial Protocol</subject><subject>Clinical Trials, Phase II as Topic</subject><subject>Germ Cells - metabolism</subject><subject>Germ-Line Mutation</subject><subject>Hamartoma Syndrome, Multiple - genetics</subject><subject>Humans</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - genetics</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>PTEN Phosphohydrolase - genetics</subject><issn>1479-6694</issn><issn>1744-8301</issn><issn>1744-8301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1vEzEQxS0Eom3gyBX5yMVl_JH1-oSiqkCkCpDI3fLa3sRo1w62N1X_exy1VHCaJ72nNzP6IfSOwjVjVH4cUyQMGCPAYf0CXVIpBOk50JdNC6lI1ylxga5K-QUgJF_Da3TBO-BKUbhEeYOPB1M83m5xqYt7wGnEu81PQqnEIeKjqcHHWvB9qAds3MlE6x0uaQoO12VOueCDyUPKIe7x3ud5CtHjH7vbb5iEaGwNp1bRvHmpTaRY3qBXo5mKf_s0V2j3-XZ385Xcff-yvdncEctpX4ngYHiv3JoraQZgne9Hx6iwTArrBXPdIGy7UnVCee6A0oHSHsD33nRS8BX69Fh7XIbZO9u-yGbSxxxmkx90MkH_78Rw0Pt00hQ4F2zNW8OHp4acfi--VD2HYv00mejTUjST0LOOqpZdIfIYtTmVkv34vIeCPnPSjZM-c9JnTi3__t_jntN_wfA_EFCOiw</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Rodón, Jordi</creator><creator>Funchain, Pauline</creator><creator>Laetsch, Theodore W</creator><creator>Arkenau, Hendrik-Tobias</creator><creator>Hervieu, Alice</creator><creator>Singer, Christian F</creator><creator>Murciano-Goroff, Yonina R</creator><creator>Chawla, Sant P</creator><creator>Anthony, Kristin</creator><creator>Yamamiya, Ikuo</creator><creator>Liu, Mei</creator><creator>Halim, Abdel-Baset</creator><creator>Benhadji, Karim A</creator><creator>Takahashi, Osamu</creator><creator>Delaloge, Suzette</creator><general>Future Medicine Ltd</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3268-346X</orcidid><orcidid>https://orcid.org/0000-0001-9027-2891</orcidid><orcidid>https://orcid.org/0000-0001-6467-3632</orcidid><orcidid>https://orcid.org/0000-0002-2015-1549</orcidid><orcidid>https://orcid.org/0000-0002-8497-3138</orcidid><orcidid>https://orcid.org/0000-0003-2106-9165</orcidid><orcidid>https://orcid.org/0000-0002-7568-8626</orcidid><orcidid>https://orcid.org/0000-0001-9883-6970</orcidid><orcidid>https://orcid.org/0000-0003-1294-0027</orcidid></search><sort><creationdate>20220901</creationdate><title>A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN -inactivating mutations</title><author>Rodón, Jordi ; Funchain, Pauline ; Laetsch, Theodore W ; Arkenau, Hendrik-Tobias ; Hervieu, Alice ; Singer, Christian F ; Murciano-Goroff, Yonina R ; Chawla, Sant P ; Anthony, Kristin ; Yamamiya, Ikuo ; Liu, Mei ; Halim, Abdel-Baset ; Benhadji, Karim A ; Takahashi, Osamu ; Delaloge, Suzette</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c318t-430a389d5397ab026e8fd214c274ce42d6b4c1179649e3d011b11800e8ea6743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Clinical Trial Protocol</topic><topic>Clinical Trials, Phase II as Topic</topic><topic>Germ Cells - metabolism</topic><topic>Germ-Line Mutation</topic><topic>Hamartoma Syndrome, Multiple - genetics</topic><topic>Humans</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - genetics</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>PTEN Phosphohydrolase - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodón, Jordi</creatorcontrib><creatorcontrib>Funchain, Pauline</creatorcontrib><creatorcontrib>Laetsch, Theodore W</creatorcontrib><creatorcontrib>Arkenau, Hendrik-Tobias</creatorcontrib><creatorcontrib>Hervieu, Alice</creatorcontrib><creatorcontrib>Singer, Christian F</creatorcontrib><creatorcontrib>Murciano-Goroff, Yonina R</creatorcontrib><creatorcontrib>Chawla, Sant P</creatorcontrib><creatorcontrib>Anthony, Kristin</creatorcontrib><creatorcontrib>Yamamiya, Ikuo</creatorcontrib><creatorcontrib>Liu, Mei</creatorcontrib><creatorcontrib>Halim, Abdel-Baset</creatorcontrib><creatorcontrib>Benhadji, Karim A</creatorcontrib><creatorcontrib>Takahashi, Osamu</creatorcontrib><creatorcontrib>Delaloge, Suzette</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Future oncology (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodón, Jordi</au><au>Funchain, Pauline</au><au>Laetsch, Theodore W</au><au>Arkenau, Hendrik-Tobias</au><au>Hervieu, Alice</au><au>Singer, Christian F</au><au>Murciano-Goroff, Yonina R</au><au>Chawla, Sant P</au><au>Anthony, Kristin</au><au>Yamamiya, Ikuo</au><au>Liu, Mei</au><au>Halim, Abdel-Baset</au><au>Benhadji, Karim A</au><au>Takahashi, Osamu</au><au>Delaloge, Suzette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN -inactivating mutations</atitle><jtitle>Future oncology (London, England)</jtitle><addtitle>Future Oncol</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>18</volume><issue>30</issue><spage>3377</spage><epage>3387</epage><pages>3377-3387</pages><issn>1479-6694</issn><issn>1744-8301</issn><eissn>1744-8301</eissn><abstract>PTEN acts as a potent tumor suppressor within the PI3K/AKT/mTOR pathway. Germline mutations in the
gene are a hallmark of PTEN hamartoma tumor syndrome, which includes Cowden syndrome, where they appear to elevate lifetime risk of cancer. Targeted AKT directed therapy has been proposed as an effective approach in cancer patients having germline
mutations. The mechanism of action, safety and dosing regimen for the novel allosteric AKT inhibitor TAS-117 have been explored in a phase I study in Japan in which activity was observed against certain tumor types. Here we describe the study protocol of an international, two-part phase II study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of TAS-117 in patients with advanced solid tumors harboring germline
-inactivating mutations.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>36039910</pmid><doi>10.2217/fon-2022-0305</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3268-346X</orcidid><orcidid>https://orcid.org/0000-0001-9027-2891</orcidid><orcidid>https://orcid.org/0000-0001-6467-3632</orcidid><orcidid>https://orcid.org/0000-0002-2015-1549</orcidid><orcidid>https://orcid.org/0000-0002-8497-3138</orcidid><orcidid>https://orcid.org/0000-0003-2106-9165</orcidid><orcidid>https://orcid.org/0000-0002-7568-8626</orcidid><orcidid>https://orcid.org/0000-0001-9883-6970</orcidid><orcidid>https://orcid.org/0000-0003-1294-0027</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1479-6694 |
| ispartof | Future oncology (London, England), 2022-09, Vol.18 (30), p.3377-3387 |
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| source | MEDLINE; PubMed Central |
| subjects | Clinical Trial Protocol Clinical Trials, Phase II as Topic Germ Cells - metabolism Germ-Line Mutation Hamartoma Syndrome, Multiple - genetics Humans Neoplasms - drug therapy Neoplasms - genetics Phosphatidylinositol 3-Kinases - genetics Proto-Oncogene Proteins c-akt - genetics PTEN Phosphohydrolase - genetics |
| title | A phase II study of TAS-117 in patients with advanced solid tumors harboring germline PTEN -inactivating mutations |
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