{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:10:50Z","timestamp":1793661050262,"version":"4.5.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Repare Therapeutics, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160\u2009mg once daily (QD) 3\u2009days on, 4 days off (160 3\/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of 120\u2009mg QD 3\/4 (120 3\/4) and 160\u2009mg QD 3\/4, 2\u2009weeks on, 1 week off (160 3\/4, 2\/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating tumor DNA (ctDNA)-based molecular response rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included 119 patients: 160 3\/4 (n\u2009=\u200967), 120 3\/4 (n\u2009=\u200925), and 160 3\/4, 2\/1w (n\u2009=\u200927) treated up to 117.1\u2009weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3\/4, 2\/1w group compared with the preliminary RP2D group (hazard ratio\u2009=\u20090.23, 2-sided P\u2009=\u2009.02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The 160 3\/4, 2\/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering a substantial reduction in the incidence of anemia without any compromise to efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial ID<\/jats:title>\n                    <jats:p>NCT04497116.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djae098","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:01:06Z","timestamp":1714608066000},"page":"1439-1449","source":"Crossref","is-referenced-by-count":20,"title":["Ataxia telangiectasia and Rad3-related (ATR) inhibitor camonsertib dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study)"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-9355","authenticated-orcid":false,"given":"Elisa","family":"Fontana","sequence":"first","affiliation":[{"name":"Sarah Cannon Research Institute UK , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra","family":"Rosen","sequence":"additional","affiliation":[{"name":"Early Drug Development and Breast Medicine Services, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth K","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"H\u00f8jgaard","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niharika B","family":"Mettu","sequence":"additional","affiliation":[{"name":"Medical Oncology, Duke University , Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Lheureux","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre , Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedito A","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Legorreta Cancer Center at Brown University and Lifespan Cancer Institute, Division of Hematology\/Oncology, Department of Medicine, The Warren Alpert Medical School, Brown University , Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-886X","authenticated-orcid":false,"given":"Gregory M","family":"Cote","sequence":"additional","affiliation":[{"name":"Mass General Cancer Center , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Carter","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, The University of Manchester , Manchester, UK"},{"name":"The Christie NHS Foundation Trust , Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-1444","authenticated-orcid":false,"given":"Ruth","family":"Plummer","sequence":"additional","affiliation":[{"name":"Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital , Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devalingam","family":"Mahalingam","sequence":"additional","affiliation":[{"name":"Robert H. 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