{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:24:10Z","timestamp":1790400250018,"version":"4.1.0"},"reference-count":17,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Patients with relapsed\/refractory (R\/R) chronic lymphocytic leukemia (CLL) have limited treatment options. Ceralasertib, a selective ataxia telangiectasia and Rad-3-related protein (ATR) inhibitor, demonstrated synergistic preclinical activity with a Bruton tyrosine kinase (BTK) inhibitor in TP53- and ATM-defective CLL cells. Acalabrutinib is a selective BTK inhibitor approved for treatment of CLL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate ceralasertib\u2009\u00b1\u2009acalabrutinib in R\/R CLL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Nonrandomized, open-label phase I\/II study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In arm A, patients received ceralasertib monotherapy 160\u2009mg twice daily (BID) continuously (cohort 1) or 2\u2009weeks on\/2\u2009weeks off (cohort 2). In arm B, patients received acalabrutinib 100\u2009mg BID continuously (cycle 1), followed by combination treatment with ceralasertib 160\u2009mg BID 1\u2009week on\/3\u2009weeks off from cycle 2. Co-primary objectives were safety and pharmacokinetics. Efficacy was a secondary objective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Eleven patients were treated [arm A, n\u2009=\u20098 (cohort 1, n\u2009=\u20095; cohort 2, n\u2009=\u20093); arm B, n\u2009=\u20093 (acalabrutinib plus ceralasertib, n\u2009=\u20092; acalabrutinib only, n\u2009=\u20091)]. Median duration of exposure was 3.5 and 7.2\u2009months for ceralasertib in arms A and B, respectively, and 15.9\u2009months for acalabrutinib in arm B. Most common grade \u2a7e3 treatment-emergent adverse events (TEAEs) in arm A were anemia (75%) and thrombocytopenia (63%), with four dose-limiting toxicities (DLTs) of grade 4 thrombocytopenia. No grade \u2a7e3 TEAEs or DLTs occurred in arm B. Ceralasertib plasma concentrations were similar when administered as monotherapy or in combination. At median follow-up of 15.1\u2009months in arm A, no responses were observed, median progression-free survival (PFS) was 3.8\u2009months, and median overall survival (OS) was 16.9\u2009months. At median follow-up of 17.2\u2009months in arm B, overall response rate was 100%, and median PFS and OS were not reached.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Ceralasertib alone showed limited clinical benefit. Acalabrutinib plus ceralasertib was tolerable with preliminary activity in patients with R\/R CLL, though findings are inconclusive due to small sample size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>NCT03328273<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20406207231173489","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T07:37:34Z","timestamp":1685432254000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Phase I\/II results of ceralasertib as monotherapy or in combination with acalabrutinib in high-risk relapsed\/refractory chronic lymphocytic leukemia"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"first","affiliation":[{"name":"Maria Sklodowska-Curie National Institute of Oncology, Garncarska 11, 31-115 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagah","family":"Elmusharaf","sequence":"additional","affiliation":[{"name":"University Hospital of Wales, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-9254","authenticated-orcid":false,"given":"Christopher P.","family":"Fox","sequence":"additional","affiliation":[{"name":"Nottingham University Hospitals, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-2448","authenticated-orcid":false,"given":"William","family":"Townsend","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-6499","authenticated-orcid":false,"given":"Amanda G.","family":"Paulovich","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-8580","authenticated-orcid":false,"given":"Jeffrey R.","family":"Whiteaker","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Krantz","sequence":"additional","affiliation":[{"name":"AstraZeneca, South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Chuan","family":"Wun","sequence":"additional","affiliation":[{"name":"AstraZeneca, South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Parr","sequence":"additional","affiliation":[{"name":"Oncology R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shringi","family":"Sharma","sequence":"additional","affiliation":[{"name":"AstraZeneca, South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-3822","authenticated-orcid":false,"given":"Veerendra","family":"Munugalavadla","sequence":"additional","affiliation":[{"name":"AstraZeneca, South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Manwani","sequence":"additional","affiliation":[{"name":"Oncology R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Dean","sequence":"additional","affiliation":[{"name":"Oncology R&D, AstraZeneca, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0769","authenticated-orcid":false,"given":"Talha","family":"Munir","sequence":"additional","affiliation":[{"name":"St. James\u2019s University Hospital, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"bibr1-20406207231173489","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806398"},{"key":"bibr2-20406207231173489","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030663"},{"key":"bibr3-20406207231173489","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-826008"},{"key":"bibr4-20406207231173489","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26367"},{"key":"bibr5-20406207231173489","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-05-644872"},{"key":"bibr6-20406207231173489","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27082491"},{"key":"bibr7-20406207231173489","unstructured":"AstraZeneca Pharmaceuticals. 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