{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:07:32Z","timestamp":1785319652897,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ataxia telangiectasia Rad3\u2010related (ATR) protein kinase regulates DNA damage response and is essential for tumor cell survival. Preclinically, ATR inhibition can sensitize tumor cells to radiation and chemotherapy. The authors conducted a phase 1 trial of berzosertib, a selective ATR inhibitor, in combination with definitive radiation and cisplatin in locally advanced head and neck squamous cell cancers (LA\u2010HNSCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      LA\u2010HNSCC patients received daily radiation (2 Gy per fraction to 70 Gy) and weekly intravenous (iv) cisplatin 40 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . Berzosertib was administered (iv) once weekly, starting with a pharmacokinetic lead\u2010in dose. Three berzosertib dose levels (DL) were tested: 120 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (DL1), 160 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (DL2), and 200 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (DL3).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty\u2010one of 43 enrolled patients were evaluable for safety and preliminary efficacy assessments. Four patients experienced dose\u2010limiting toxicities (DLTs) in dose\u2010escalation: grade 4 thrombocytopenia (1), grade 4 respiratory failure (1), grade 3 renal injury and hypoxia (1), and inability to receive 90% of the planned radiation dose (1). DL3 was the recommended phase 2 dose, and 15 patients were enrolled at this DL as an expansion cohort. Objective response rates (ORR) in patient cohorts treated with any amount of berzosertib; treated with at least 50% of planned treatment; and in the expansion cohort were 78.8% (26 of 33), 78.8% (26 of 33), and 63.6% (7 of 11), respectively, after excluding eight inevaluable patients without post\u2010treatment imaging assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Berzosertib (200 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      iv weekly) was safe when combined with chemoradiation but did not improve complete response rate in LA\u2010HNSCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70346","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:26:31Z","timestamp":1773408391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A phase 1 study of berzosertib (M6620, VX\u2010970) in combination with cisplatin and radiation in patients with locally advanced head and neck squamous cell carcinoma (ETCTN\u00a09950)"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-4454","authenticated-orcid":false,"given":"Aarti","family":"Bhatia","sequence":"first","affiliation":[{"name":"Yale School of Medicine and Yale Cancer Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjia","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Biostatistics University of Illinois at Chicago  Chicago Illinois 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