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The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity \u226510%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting \u226516\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8\u2009months (95% CI, 1.6\u20131.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8\u2009months (range, 0.1\u201310.1). Most frequent any-grade treatment-emergent adverse events were asthenia\/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious\n                      <jats:italic>BRCA1<\/jats:italic>\n                      or\n                      <jats:italic>BRCA2<\/jats:italic>\n                      alteration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      This trial was registered in\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017\u2013004166-10).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-021-08085-z","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T08:02:51Z","timestamp":1621843371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3965-3394","authenticated-orcid":false,"given":"P.","family":"Grivas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Loriot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Morales-Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Patients provided written informed consent before participation.The study was approved by the following institutional review boards and ethics committees for participating centers: AEMPS (Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios); Agenzia Italiana del Farmaco \u2013 OsSC; AIFA (Agenzia Italiana del Farmaco); ANSM (Agence Nationale de S\u00e9curit\u00e9 du M\u00e9dicament et des Produits de Sant\u00e9); BfArM (Bundesinstitut fur Arzneimittel und Medizinprodukte); CCP Ouest II (Angers); CEIm Parc de Salut Mar; Comitato Etico Area Vasta Emilia Centro; Comitato Etico della Fondazione IRCCS Istituto Nazionale dei Tumori; Comitato Etico Ospedale San Raffaele; Comitato Etico Universit\u00e1 Federico II; DUHS IRB; Fondazione del Piemonte per l\u2019Ongologia-IRCCS Candiolo; Georgetown University IRB; Landes\u00e4rztekammer Baden<i>-<\/i>W\u00fcrttemberg; Medical College of Wisconsin-Froedtert Hospital IRB; Memorial Sloan-Kettering Cancer Center IRB; MHRA Regulatory Medicines and Medical Devices; NHS Health Research Authority; Oregon Health and Science IRB; Oschner Clinic Foundation IRB; Providence Health & Services IRB; Quorum; Research Compliance Office, Stanford University; Roswell Park IRB; UCLA OHRPP; University of California, San Diego Human Research Protections Program; University of Iowa IRB; University of Maryland IRB; University of Utah IRB; US Oncology, Inc. IRB; UT Health Committee for the Protection of Human Subjects; Weill Cornell Medical College IRB; WIRB (Western Institutional Review Board).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PG has served in a consulting role for and has received fees from Clovis Oncology, AstraZeneca, Bayer, Bristol-Myers Squibb, Driver, Dyania Health, EMD Serono, Exelixis, Foundation Medicine, Genentech, Genzyme, GlaxoSmithKline, Heron Therapeutics, Immunomedics, Infinity Pharmaceuticals, Janssen, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics, Roche, and Seattle Genetics; his current institution, University of Washington, received research funding from Clovis Oncology related to this study and from Bavarian Nordic, Bristol-Myers Squibb, Debiopharm, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck, Mirati Therapeutics, Pfizer, and QED Therapeutics unrelated to this study; and his former institution, Cleveland Clinic, received research funding from AstraZeneca, Bayer, Genentech, Merck, Mirati Therapeutics, OncoGenex, and Pfizer unrelated to this study; also acknowledges support from Seattle Translational Tumor Research Program at Fred Hutchinson Cancer Research Center. YL has served in a consulting or advisory role for Astellas, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Pfizer, Roche, and Seattle Genetics, and has received research funding from Johnson & Johnson, Merck Sharp & Dohme, and Sanofi. RM-B has served in a consulting or advisory role and\/or on the speakers bureaus for Asofarma, AstraZeneca, Bayer, Janssen, Merck Sharp & Dohme, and Sanofi Aventis, and has received travel and accommodation expenses from Clovis Oncology, Astellas, Bayer, Janssen, Lilly, Merck Sharp & Dohme, Pharmacyclics, Roche, and Sanofi Aventis. MYT has received research funding as principal investigator of clinical trials from Clovis Oncology and Bristol-Myers Squibb. YZ has served on advisory boards for Amgen, Castle Bioscience, Eisai, Exelixis, Johnson & Johnson, Novartis, Pfizer, and Roche Diagnostics. SF has served on advisory boards for Aventis, Astellas, and Janssen and received travel and accommodation expenses from Aventis and Janssen. NJV has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Fuji, Janssen, Merck, Pfizer, Roche, and Tolero; is on the speakers bureaus for Bayer, Exelixis, and Sanofi Aventis; has stock options in Caris; has provided legal services to Novartis; and serves on the editorial board of <i>Up-To-Date<\/i>. EG has received honoraria for advisory boards, meetings, and\/or lectures from Pfizer, Bristol-Myers Squibb, Ipsen, Roche, Eisai, EUSA Pharma, Merck Sharp & Dohme, Sanofi-Genzyme, Adacap, Novartis, Pierre Fabre, Lexicon and Celgene; has received unrestricted research grants from Pfizer, Astra Zeneca, Molecular Templates\/Threshold, Roche, Ipsen, and Lexicon. NA declares no competing interests. AA has served on advisory boards for AstraZeneca, Merck, and Bristol-Myers Squibb, and has received research funding from Clovis Oncology, AstraZeneca, Bayer, Bristol-Myers Squibb, Esanik, Genentech, Ionis, Janssen, Merck, Progenics, and Prometheus. AN has served in a consulting or advisory role for Clovis Oncology, AstraZeneca, Bayer, BioClin Therapeutics, Bristol-Myers Squibb, Incyte, Janssen, Merck, and Roche, and has received research funding from AstraZeneca and Merck. AR-V has served in a consulting or advisory role and\/or on the speakers bureaus for Clovis Oncology, Astellas, Bayer, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Pfizer, and Roche; received honoraria from AstraZeneca and Sanofi Aventis; and received research funding from Merck Sharp & Dohme, Pfizer, and Takeda. SG declares no competing interests. DHJ has participated in an unbranded educational speaker program with Pfizer, and received travel and accommodation expenses from EUSA Pharma and Ipsen. SS has served in an advisory role for Clovis Oncology. KW, DT<b>,<\/b> AS, AL<b>,<\/b> RLD<b>,<\/b> and DN are employees of Clovis Oncology and may own stock or have stock options in that company. SC has served in a consulting or advisory role and\/or on speakers bureaus for Clovis Oncology, Astellas Pharma, Bayer, BeiGene Janssen, Pfizer, and Sanofi; received honoraria from GlaxoSmithKline and Novartis; and received research funding from Clovis Oncology, Johnson & Johnson, and Sanofi.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"593"}}