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We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on\/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and\/or deleterious ATM mutations and received doses \u226540 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and\/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population.<\/jats:p>\n                    <jats:p>See related commentary by Italiano, p. 14.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-20-0868","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:13Z","timestamp":1601337613000},"page":"80-91","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":245,"title":["First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors"],"prefix":"10.1158","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-3309","authenticated-orcid":false,"given":"Timothy A.","family":"Yap","sequence":"first","affiliation":[{"name":"1The University of Texas MD Anderson Cancer Center, Houston, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-5262","authenticated-orcid":false,"given":"David S.P.","family":"Tan","sequence":"additional","affiliation":[{"name":"2National University Cancer Institute and National University Hospital and Cancer Science Institute, National University of Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Terbuch","sequence":"additional","affiliation":[{"name":"3The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom."},{"name":"4Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reece","family":"Caldwell","sequence":"additional","affiliation":[{"name":"3The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1645-3202","authenticated-orcid":false,"given":"Christina","family":"Guo","sequence":"additional","affiliation":[{"name":"3The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boon Cher","family":"Goh","sequence":"additional","affiliation":[{"name":"2National University Cancer Institute and National University Hospital and Cancer Science Institute, National University of Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-1355","authenticated-orcid":false,"given":"Valerie","family":"Heong","sequence":"additional","affiliation":[{"name":"2National University Cancer Institute and National University Hospital and Cancer Science Institute, National University of Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor R. 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