Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer
Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein. Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m on D1, D8, D15)...
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| Veröffentlicht in: | Clinical cancer research 2021-09, Vol.27 (17), p.4700-4709 |
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| creator | Kim, Seung Tae Smith, Simon A Mortimer, Peter Loembé, Arsene-Bienvenu Cho, Heejin Kim, Kyoung-Mee Smith, Claire Willis, Sophie Irurzun-Arana, Itziar Berges, Alienor Hong, Jung Yong Park, Se Hoon Park, Joon Oh Park, Young Suk Lim, Ho Yeong Kang, Won Ki Kozarewa, Iwanka Pierce, Andrew J Dean, Emma Lee, Jeeyun |
| description | Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.
Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m
on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.
The RP2D was established as ceralasertib 240 mg BD days 1-14 plus paclitaxel 80 mg/m
on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (
= 39, 68%), anemia (
= 25, 44%), and thrombocytopenia (
= 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5-35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0-51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0-5.8), the median duration of response was 9.9 months (95% CI, 3.7-23.2), and the mOS was 7.4 months (95% CI, 5.7-11.9).
Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-21-0251 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8974415</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33975862</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-667d561f8ef273030db55a4c00205b813e912202d7b52c1aca993835862ad7003</originalsourceid><addsrcrecordid>eNpVUU1P3DAQtVARUMpPaDXHViLUY8dxckFaZVuKhABtWyH1Yk0cZ9clm6ycQLt3fngd8aFymtHMvDcz7zH2HvkJoso_I9d5wlMpTspykQhMuFC4ww5QKZ1Ikak3MX-e2Wdvh-E355giT_fYvpSFVnkmDtjD9YoGB-fwfbyrt9A3ULpAbayF0VfwcfZrnmmZfzoGgsv-3rUwv5zBnNa0dLBwG_IBZkvXjcfgOyj7deU7Gn3fwR8_ruDGudt2C9dkWz_S3wiPUwvXBLJjH7ZQUmddeMd2G2oHd_QUD9nPr19-lN-Si6uz83J2kdgUcUyyTNcqwyZ3jdCSS15XSlFqORdcVTlKV6AQXNS6UsIiWSoKmcvpUao15_KQnT7ybu6qtattPDv-ajbBrylsTU_evO50fmWW_b3JC52mqCKBeiSwoR-G4JoXLHIz2WImyc0kuYm2GIFmsiXiPvy_-AX17IP8B8d0h80</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Kim, Seung Tae ; Smith, Simon A ; Mortimer, Peter ; Loembé, Arsene-Bienvenu ; Cho, Heejin ; Kim, Kyoung-Mee ; Smith, Claire ; Willis, Sophie ; Irurzun-Arana, Itziar ; Berges, Alienor ; Hong, Jung Yong ; Park, Se Hoon ; Park, Joon Oh ; Park, Young Suk ; Lim, Ho Yeong ; Kang, Won Ki ; Kozarewa, Iwanka ; Pierce, Andrew J ; Dean, Emma ; Lee, Jeeyun</creator><creatorcontrib>Kim, Seung Tae ; Smith, Simon A ; Mortimer, Peter ; Loembé, Arsene-Bienvenu ; Cho, Heejin ; Kim, Kyoung-Mee ; Smith, Claire ; Willis, Sophie ; Irurzun-Arana, Itziar ; Berges, Alienor ; Hong, Jung Yong ; Park, Se Hoon ; Park, Joon Oh ; Park, Young Suk ; Lim, Ho Yeong ; Kang, Won Ki ; Kozarewa, Iwanka ; Pierce, Andrew J ; Dean, Emma ; Lee, Jeeyun</creatorcontrib><description>Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.
Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m
on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.
The RP2D was established as ceralasertib 240 mg BD days 1-14 plus paclitaxel 80 mg/m
on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (
= 39, 68%), anemia (
= 25, 44%), and thrombocytopenia (
= 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5-35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0-51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0-5.8), the median duration of response was 9.9 months (95% CI, 3.7-23.2), and the mOS was 7.4 months (95% CI, 5.7-11.9).
Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-21-0251</identifier><identifier>PMID: 33975862</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject><![CDATA[Adult ; Aged ; Antineoplastic Agents, Phytogenic - administration & dosage ; Clinical Trials: Targeted Therapy ; Drug Administration Schedule ; Drug Combinations ; Female ; Humans ; Indoles - administration & dosage ; Male ; Melanoma - drug therapy ; Middle Aged ; Morpholines - administration & dosage ; Neoplasms - drug therapy ; Paclitaxel - administration & dosage ; Pyrimidines - administration & dosage ; Skin Neoplasms - drug therapy ; Sulfonamides - administration & dosage]]></subject><ispartof>Clinical cancer research, 2021-09, Vol.27 (17), p.4700-4709</ispartof><rights>2021 The Authors; Published by the American Association for Cancer Research.</rights><rights>2021 The Authors; Published by the American Association for Cancer Research 2021 American Association for Cancer Research</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-667d561f8ef273030db55a4c00205b813e912202d7b52c1aca993835862ad7003</citedby><cites>FETCH-LOGICAL-c411t-667d561f8ef273030db55a4c00205b813e912202d7b52c1aca993835862ad7003</cites><orcidid>0000-0002-1162-9205 ; 0000-0001-6502-2612 ; 0000-0001-9062-0307 ; 0000-0001-7335-1846 ; 0000-0003-2900-2336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33975862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Seung Tae</creatorcontrib><creatorcontrib>Smith, Simon A</creatorcontrib><creatorcontrib>Mortimer, Peter</creatorcontrib><creatorcontrib>Loembé, Arsene-Bienvenu</creatorcontrib><creatorcontrib>Cho, Heejin</creatorcontrib><creatorcontrib>Kim, Kyoung-Mee</creatorcontrib><creatorcontrib>Smith, Claire</creatorcontrib><creatorcontrib>Willis, Sophie</creatorcontrib><creatorcontrib>Irurzun-Arana, Itziar</creatorcontrib><creatorcontrib>Berges, Alienor</creatorcontrib><creatorcontrib>Hong, Jung Yong</creatorcontrib><creatorcontrib>Park, Se Hoon</creatorcontrib><creatorcontrib>Park, Joon Oh</creatorcontrib><creatorcontrib>Park, Young Suk</creatorcontrib><creatorcontrib>Lim, Ho Yeong</creatorcontrib><creatorcontrib>Kang, Won Ki</creatorcontrib><creatorcontrib>Kozarewa, Iwanka</creatorcontrib><creatorcontrib>Pierce, Andrew J</creatorcontrib><creatorcontrib>Dean, Emma</creatorcontrib><creatorcontrib>Lee, Jeeyun</creatorcontrib><title>Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.
Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m
on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.
The RP2D was established as ceralasertib 240 mg BD days 1-14 plus paclitaxel 80 mg/m
on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (
= 39, 68%), anemia (
= 25, 44%), and thrombocytopenia (
= 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5-35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0-51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0-5.8), the median duration of response was 9.9 months (95% CI, 3.7-23.2), and the mOS was 7.4 months (95% CI, 5.7-11.9).
Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents, Phytogenic - administration & dosage</subject><subject>Clinical Trials: Targeted Therapy</subject><subject>Drug Administration Schedule</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>Humans</subject><subject>Indoles - administration & dosage</subject><subject>Male</subject><subject>Melanoma - drug therapy</subject><subject>Middle Aged</subject><subject>Morpholines - administration & dosage</subject><subject>Neoplasms - drug therapy</subject><subject>Paclitaxel - administration & dosage</subject><subject>Pyrimidines - administration & dosage</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Sulfonamides - administration & dosage</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1P3DAQtVARUMpPaDXHViLUY8dxckFaZVuKhABtWyH1Yk0cZ9clm6ycQLt3fngd8aFymtHMvDcz7zH2HvkJoso_I9d5wlMpTspykQhMuFC4ww5QKZ1Ikak3MX-e2Wdvh-E355giT_fYvpSFVnkmDtjD9YoGB-fwfbyrt9A3ULpAbayF0VfwcfZrnmmZfzoGgsv-3rUwv5zBnNa0dLBwG_IBZkvXjcfgOyj7deU7Gn3fwR8_ruDGudt2C9dkWz_S3wiPUwvXBLJjH7ZQUmddeMd2G2oHd_QUD9nPr19-lN-Si6uz83J2kdgUcUyyTNcqwyZ3jdCSS15XSlFqORdcVTlKV6AQXNS6UsIiWSoKmcvpUao15_KQnT7ybu6qtattPDv-ajbBrylsTU_evO50fmWW_b3JC52mqCKBeiSwoR-G4JoXLHIz2WImyc0kuYm2GIFmsiXiPvy_-AX17IP8B8d0h80</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Kim, Seung Tae</creator><creator>Smith, Simon A</creator><creator>Mortimer, Peter</creator><creator>Loembé, Arsene-Bienvenu</creator><creator>Cho, Heejin</creator><creator>Kim, Kyoung-Mee</creator><creator>Smith, Claire</creator><creator>Willis, Sophie</creator><creator>Irurzun-Arana, Itziar</creator><creator>Berges, Alienor</creator><creator>Hong, Jung Yong</creator><creator>Park, Se Hoon</creator><creator>Park, Joon Oh</creator><creator>Park, Young Suk</creator><creator>Lim, Ho Yeong</creator><creator>Kang, Won Ki</creator><creator>Kozarewa, Iwanka</creator><creator>Pierce, Andrew J</creator><creator>Dean, Emma</creator><creator>Lee, Jeeyun</creator><general>American Association for Cancer Research</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/0000-0002-1162-9205</orcidid><orcidid>https://orcid.org/0000-0001-6502-2612</orcidid><orcidid>https://orcid.org/0000-0001-9062-0307</orcidid><orcidid>https://orcid.org/0000-0001-7335-1846</orcidid><orcidid>https://orcid.org/0000-0003-2900-2336</orcidid></search><sort><creationdate>20210901</creationdate><title>Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer</title><author>Kim, Seung Tae ; Smith, Simon A ; Mortimer, Peter ; Loembé, Arsene-Bienvenu ; Cho, Heejin ; Kim, Kyoung-Mee ; Smith, Claire ; Willis, Sophie ; Irurzun-Arana, Itziar ; Berges, Alienor ; Hong, Jung Yong ; Park, Se Hoon ; Park, Joon Oh ; Park, Young Suk ; Lim, Ho Yeong ; Kang, Won Ki ; Kozarewa, Iwanka ; Pierce, Andrew J ; Dean, Emma ; Lee, Jeeyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-667d561f8ef273030db55a4c00205b813e912202d7b52c1aca993835862ad7003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents, Phytogenic - administration & dosage</topic><topic>Clinical Trials: Targeted Therapy</topic><topic>Drug Administration Schedule</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>Humans</topic><topic>Indoles - administration & dosage</topic><topic>Male</topic><topic>Melanoma - drug therapy</topic><topic>Middle Aged</topic><topic>Morpholines - administration & dosage</topic><topic>Neoplasms - drug therapy</topic><topic>Paclitaxel - administration & dosage</topic><topic>Pyrimidines - administration & dosage</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Sulfonamides - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Seung Tae</creatorcontrib><creatorcontrib>Smith, Simon A</creatorcontrib><creatorcontrib>Mortimer, Peter</creatorcontrib><creatorcontrib>Loembé, Arsene-Bienvenu</creatorcontrib><creatorcontrib>Cho, Heejin</creatorcontrib><creatorcontrib>Kim, Kyoung-Mee</creatorcontrib><creatorcontrib>Smith, Claire</creatorcontrib><creatorcontrib>Willis, Sophie</creatorcontrib><creatorcontrib>Irurzun-Arana, Itziar</creatorcontrib><creatorcontrib>Berges, Alienor</creatorcontrib><creatorcontrib>Hong, Jung Yong</creatorcontrib><creatorcontrib>Park, Se Hoon</creatorcontrib><creatorcontrib>Park, Joon Oh</creatorcontrib><creatorcontrib>Park, Young Suk</creatorcontrib><creatorcontrib>Lim, Ho Yeong</creatorcontrib><creatorcontrib>Kang, Won Ki</creatorcontrib><creatorcontrib>Kozarewa, Iwanka</creatorcontrib><creatorcontrib>Pierce, Andrew J</creatorcontrib><creatorcontrib>Dean, Emma</creatorcontrib><creatorcontrib>Lee, Jeeyun</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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Seung Tae</au><au>Smith, Simon A</au><au>Mortimer, Peter</au><au>Loembé, Arsene-Bienvenu</au><au>Cho, Heejin</au><au>Kim, Kyoung-Mee</au><au>Smith, Claire</au><au>Willis, Sophie</au><au>Irurzun-Arana, Itziar</au><au>Berges, Alienor</au><au>Hong, Jung Yong</au><au>Park, Se Hoon</au><au>Park, Joon Oh</au><au>Park, Young Suk</au><au>Lim, Ho Yeong</au><au>Kang, Won Ki</au><au>Kozarewa, Iwanka</au><au>Pierce, Andrew J</au><au>Dean, Emma</au><au>Lee, Jeeyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>27</volume><issue>17</issue><spage>4700</spage><epage>4709</epage><pages>4700-4709</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Ceralasertib is a potent and selective oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related (ATR) protein.
Eligible patients with solid tumors, enriched for melanoma, received ceralasertib in combination with a fixed dose of paclitaxel (80 mg/m
on D1, D8, D15) in 28-day cycles. The dose of ceralasertib was escalated to reach an MTD in a rolling 6 design. The starting dose of ceralasertib was 40 mg QD. Fifty-seven patients (33 patients with melanoma who failed prior PD1/L1 treatment) were enrolled in 7 dose cohorts ranging from 40 mg QD to 240 mg BD plus weekly paclitaxel.
The RP2D was established as ceralasertib 240 mg BD days 1-14 plus paclitaxel 80 mg/m
on D1, D8, D15 every 28 days. The most common toxicities were neutropenia (
= 39, 68%), anemia (
= 25, 44%), and thrombocytopenia (
= 21, 37%). In the full analysis set of 57 patients, the overall response rate (ORR) was 22.6% (95% CI, 12.5-35.3). In 33 patients with melanoma, resistant to prior anti-PD1 therapy, the ORR was 33.3% (95% CI, 18.0-51.8). In the melanoma subset, the mPFS was 3.6 months (95% CI, 2.0-5.8), the median duration of response was 9.9 months (95% CI, 3.7-23.2), and the mOS was 7.4 months (95% CI, 5.7-11.9).
Ceralasertib in combination with paclitaxel was well tolerated in patients with advanced malignancies and showed evidence of antitumor activity. Durable responses were observed in patients with advanced cutaneous, acral, and mucosal melanoma resistant to anti-PD1/L1 treatment.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>33975862</pmid><doi>10.1158/1078-0432.CCR-21-0251</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1162-9205</orcidid><orcidid>https://orcid.org/0000-0001-6502-2612</orcidid><orcidid>https://orcid.org/0000-0001-9062-0307</orcidid><orcidid>https://orcid.org/0000-0001-7335-1846</orcidid><orcidid>https://orcid.org/0000-0003-2900-2336</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2021-09, Vol.27 (17), p.4700-4709 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antineoplastic Agents, Phytogenic - administration & dosage Clinical Trials: Targeted Therapy Drug Administration Schedule Drug Combinations Female Humans Indoles - administration & dosage Male Melanoma - drug therapy Middle Aged Morpholines - administration & dosage Neoplasms - drug therapy Paclitaxel - administration & dosage Pyrimidines - administration & dosage Skin Neoplasms - drug therapy Sulfonamides - administration & dosage |
| title | Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer |
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