{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:50:54Z","timestamp":1789498254893,"version":"build-2803163510"},"reference-count":5,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["2UM1CA186691-06 and 2UM1CA186690-06"],"award-info":[{"award-number":["2UM1CA186691-06 and 2UM1CA186690-06"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with treatment-na\u00efve extensive-stage SCLC, ECOG \u22642 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad221","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T08:29:28Z","timestamp":1691569768000},"page":"1007-e1107","source":"Crossref","is-referenced-by-count":14,"title":["Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8983-6677","authenticated-orcid":false,"given":"Ryan D","family":"Gentzler","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Virginia Cancer Center , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-523X","authenticated-orcid":false,"given":"Liza C","family":"Villaruz","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pittsburgh Medical Center-Hillman Cancer Center , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Rhee","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Pittsburgh Medical Center-Hillman Cancer Center , Pittsburgh, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-4626","authenticated-orcid":false,"given":"Bethany","family":"Horton","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Virginia School of Medicine , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Mock","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of Virginia Cancer Center , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-1055","authenticated-orcid":false,"given":"Michael","family":"Hanley","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging, University of Virginia , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University , Columbus, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-6868","authenticated-orcid":false,"given":"Michelle A","family":"Rudek","sequence":"additional","affiliation":[{"name":"Department of Oncology and Medicine, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-5280","authenticated-orcid":false,"given":"Mitch A","family":"Phelps","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University , Columbus, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-1215","authenticated-orcid":false,"given":"Michael A","family":"Carducci","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-7893","authenticated-orcid":false,"given":"Richard","family":"Piekarz","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, National Cancer Institute , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-9086","authenticated-orcid":false,"given":"Kwon-Sik","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia Cancer Center , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-3261","authenticated-orcid":false,"given":"Timothy N","family":"Bullock","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia Cancer Center , Charlottesville, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5204-3465","authenticated-orcid":false,"given":"Charles M","family":"Rudin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"2023110708533996200_CIT0001","first-page":"1422","article-title":"Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition","volume-title":"Cancer \u00adDiscov","author":"Jia","year":"2018"},{"key":"2023110708533996200_CIT0002","first-page":"114156","article-title":"HDAC inhibition potentiates immunotherapy in triple negative breast cancer","volume-title":"Oncotarget","author":"Terranova-Barberio","year":"2017"},{"key":"2023110708533996200_CIT0003","first-page":"4119","article-title":"HDAC inhibitors enhance T-cell chemokine expression and augment response to PD-1 immunotherapy in lung adenocarcinoma","volume-title":"Clin Cancer Res","author":"Zheng","year":"2016"},{"key":"2023110708533996200_CIT0004","first-page":"S330","article-title":"OA05.01 efficacy\/safety of entinostat (ENT) and pembrolizumab (PEMBRO) in NSCLC patients previously treated with anti-PD-(L)1 therapy","volume-title":"J Thoracic Oncol","author":"Hellmann","year":"2018"},{"key":"2023110708533996200_CIT0005","first-page":"507","article-title":"Bayesian optimal interval designs for phase I clinical trials","volume-title":"J R Stat Soc C","author":"Liu","year":"2015"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/28\/11\/1007\/52772332\/oyad221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/28\/11\/1007\/52772332\/oyad221.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T08:54:41Z","timestamp":1699347281000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/28\/11\/1007\/7239521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":5,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,8,9]]},"published-print":{"date-parts":[[2023,11,2]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyad221","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11,1]]},"published":{"date-parts":[[2023,8,9]]}}}