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Baseline plasma ctDNA samples were analyzed to determine the <jats:italic>ESR1<\/jats:italic> mutation status.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Patients (<jats:italic>N<\/jats:italic>\u2009=\u2009152) received GDC-0810 100\u2013800\u00a0mg once daily (QD) or 300\u2013400\u00a0mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600\u00a0mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (&gt;\u200990%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring <jats:italic>ESR1<\/jats:italic> mutations included partial responses (4% overall; 4% <jats:italic>ESR1<\/jats:italic>), stable disease (39% overall; 42% <jats:italic>ESR1<\/jats:italic>), non-complete response\/non-progressive disease (13% overall; 12% <jats:italic>ESR1<\/jats:italic>), progressive disease (40% overall; 38% <jats:italic>ESR1<\/jats:italic>), and missing\/unevaluable (5% overall; 5% <jats:italic>ESR1<\/jats:italic>). Clinical benefit (responses or SD, lasting\u2009\u2265\u200924\u00a0weeks) was observed in patients in dose escalation (<jats:italic>n<\/jats:italic>\u2009=\u200916, 39%) and expansion (<jats:italic>n<\/jats:italic>\u2009=\u200924, 22%).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>GDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER\u2009+\u2009advanced\/MBC, with\/without <jats:italic>ESR1<\/jats:italic> mutations, highlighting the potential for oral SERDs.<\/jats:p>\n                <jats:p><jats:italic>Clinical Trial and registration date<\/jats:italic> April 4, 2013. NCT01823835 .<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10549-022-06797-9","type":"journal-article","created":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T13:02:32Z","timestamp":1668862952000},"page":"319-331","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR\u2009+\u2009\/HER2\u2009\u2212) advanced\/metastatic breast cancer"],"prefix":"10.1007","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-1157","authenticated-orcid":false,"given":"Aditya","family":"Bardia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Winer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia X.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Bellet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos L.","family":"Arteaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sravanthi","family":"Cheeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Gates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Wei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Fredrickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill M.","family":"Spoerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Giltnane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori S.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Chow Maneval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Jhaveri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"issue":"2","key":"6797_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107[published","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. 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I.M. received consulting fees\/ research support from Genentech and is an employee of AstraZeneca. E.W. and H.M.L. received consulting fees and research support from Genentech. C.X.M. held consulting\/advisory board positions at Gilead, AstraZeneca, Sanofi-Genzyme, Jacobio, Natera, Novartis, Inivata, Biovica, Athenex, Bayer, Esai, and OncoSignal and received funding from Pfizer and Puma. B.A.P. received contracted research support to the institution from Pfizer, Novartis, Glaxo Smith Kline, Genentech\/Roche, and Oncternal Therapeutics Inc., consulting fees from Dare Bioscience, Bioatla Inc. (spouse), EMD Serona (spouse), and Samumed LLC (spouse), and has stock ownership in Merck. M.B. held advisory board positions at Pfizer, Novartis, and Lilly and received speakers bureau fees from Pfizer, Novartis, and Lilly and travel expenses from Pfizer and Roche. C.L.A. held advisory board positions at Novartis, Lilly, Merck, TAIHO Oncology, Immunomedics, Daiichi Sankyo, AstraZeneca, Sanofi, OrigiMed, and Susan G. Komen Foundation, received research grant support from Pfizer, Lilly, and Takeda, and has stock ownership in Provista. S.C., M.G., C.-W.C., J.F., H.M.M., J.G., and I.C. are employees and stockholders of Roche\/Genentech. J.M.S. and L.S.F. are former employees and stockholders of Roche\/Genentech. E.C.M. is a former employee of Seragon. K.J. received consulting fees from AbbVie, AstraZeneca, Blueprint Medicines, Biotheranostics, BMS, Genentech, Jounce Therapeutics, Lilly Pharmaceuticals, Novartis, Pfizer, Seattle Genetics, SunPharma Pvt Ltd, and Taiho Oncology and contracted research grants to institution from ADC Therapeutics, AstraZeneca, Clovis Oncology, Debio Pharmaceuticals, Genentech, Immunomedics, Novartis, Lilly Pharmaceuticals, Merck\/VelosBio, Novartis, Novita Pharmaceuticals, Pfizer, Puma Biotechnology, and Zymeworks.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}},{"value":"The appropriate research ethics committee at each clinic where patients were enrolled approved the study: (1) Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021. (2) Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114. (3) Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215. (4) Seattle Cancer Care Alliance, 825 Eastlake Ave., Seattle, WA 98109. (5) Washington University, 660 S. Euclid Ave., St. Louis, MO 63110. (6) UCSD Medical Center, 3855 Health Sciences Dr., La Jolla, CA 92093. (7) Vanderbilt University Medical Center, 2220 Pierce Ave., Nashville, TN, 37232. (8) Hospital Universitari Vall d\u2019Hebron, Passeig de la Vall d\u2019Hebron, 119\u2013129, 08035, Barcelona, Spain. (9) Severance Hospital, Yonsei University Health System, 50 Yonsei-ro, Seodaemun-Gu, 120\u2013752, Seoul, South Korea. (10) Centro Integral Oncologico Clara Campal (CIOCC), Calle O\u00f1a N\u00b010, 28050, Madrid, Spain. (11) Mount Sinai Medical Center, 1176 Fifth Ave., New York, NY 10029. (12) Vu Medisch Centrum, Dept. Medical Oncology, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. (13) Seoul National University Cancer Hospital, 101 Daehak-ro, Jogno-gu 110\u2013744, Seoul, South Korea. (14) Hospital Clinico Universitario de Valencia, Avda Basco Ibanez 17, 46010, Valencia, Spain.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}