{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T04:30:15Z","timestamp":1750307415305},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova\u2010T) is an antibody\u2010drug conjugate that targets delta\u2010like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova\u2010T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova\u2010T in patients with previously treated extensive\u2010stage SCLC. Patients underwent ECG monitoring for 2\u00a0weeks after each of 2 i.v. infusions of 0.3\u00a0mg\/kg Rova\u2010T over 30\u00a0minutes, administered 6\u00a0weeks apart. Forty\u2010six patients received at least one dose of Rova\u2010T. At the geometric mean Rova\u2010T maximum serum concentration of 7,940\u00a0ng\/mL, ECG monitoring showed no significant changes in the Fridericia\u2010corrected QT (QTcF) interval; the upper limit of the 2\u2010sided 90% confidence interval did not exceed 10\u00a0msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova\u2010T administration. All patients experienced a treatment\u2010emergent AE (TEAE); 78% had a grade \u2265\u00a03 TEAE, 59% had a serious TEAE, and 41% had a cardiac\u2010related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova\u2010T at 0.3\u00a0mg\/kg i.v. administered every 6\u00a0weeks, a QTcF effect of clinical concern can be excluded.<\/jats:p>","DOI":"10.1111\/cts.12928","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T07:45:46Z","timestamp":1608363946000},"page":"664-670","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small\u2010Cell Lung Cancer"],"prefix":"10.1111","volume":"14","author":[{"given":"Jonathan W.","family":"Goldman","sequence":"first","affiliation":[{"name":"David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minal","family":"Barve","sequence":"additional","affiliation":[{"name":"Mary Crowley Cancer Research Center Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyoti D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Lurie Cancer Center of Northwestern University Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoinette","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Hillman Cancer Center at University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afshin","family":"Dowlati","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Starodub","sequence":"additional","affiliation":[{"name":"Riverside Peninsula Cancer Institute Newport News Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taofeek K.","family":"Owonikoko","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Edenfield","sequence":"additional","affiliation":[{"name":"Prisma Health Cancer Institute Greenville South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Laurie","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Da Costa","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. Illinois North Chicago USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satwant","family":"Lally","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. Illinois North Chicago USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Koch","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. Illinois North Chicago USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew P.","family":"Kosloski","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. Illinois North Chicago USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hoffman","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. Illinois North Chicago USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace K.","family":"Dy","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"American Cancer Society.Cancer facts & figures 2019(American Cancer Society Atlanta GA). <https:\/\/www.cancer.org\/research\/cancer\u2010facts\u2010statistics\/all\u2010cancer\u2010facts\u2010figures\/cancer\u2010facts\u2010figures\u20102019.html> (2019). Accessed May 19 2020."},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2013.0011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24223-1_1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00105009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0298"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40389-2_14"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0736-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.5821"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac9459"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30565-4"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1133"},{"key":"e_1_2_10_12_1","unstructured":"AbbVie discontinues rovalpituzumab tesirine (Rova\u2010T) research and development program.North Chicago IL:AbbVie Inc.; August 29 2019 <https:\/\/news.abbvie.com\/news\/press\u2010releases\/abbvie\u2010discontinues\u2010rovalpituzumab\u2010tesirine\u2010rova\u2010t\u2010research\u2010and\u2010development\u2010program.htm>. Accessed October 23 2019."},{"key":"e_1_2_10_13_1","unstructured":"Phase 3 trial of Rova\u2010T as second\u2010line therapy for advanced small\u2010cell lung cancer (TAHOE Study) Halted.North Chicago IL:AbbVie Inc.; December 5 2018 <https:\/\/news.abbvie.com\/news\/phase\u20103\u2010trial\u2010rova\u2010t\u2010as\u2010second\u2010line\u2010therapy\u2010for\u2010advanced\u2010small\u2010cell\u2010lung\u2010cancer\u2010tahoe\u2010study\u2010halted.htm>. Accessed October 23 2019."},{"key":"e_1_2_10_14_1","unstructured":"E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010anti\u2010arrhythmic drugs.US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) and Center for Biologicals Evaluation and Research (CBER)<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e14\u2010clinical\u2010evaluation\u2010qtqtc\u2010interval\u2010prolongation\u2010and\u2010proarrhythmic\u2010potential\u2010non\u2010antiarrhythmic\u20100> (2005). Accessed April 6 2020."},{"key":"e_1_2_10_15_1","unstructured":"Clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010anti\u2010arrhythmic drugs questions and answers (R3) guidance for industry.US Department of Health and Human Services Food and Drug Administration. Center for Drug Evaluation and Research (CDER) and Center for Biologicals Evaluation and Research (CBER)<https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e14\u2010clinical\u2010evaluation\u2010qtqtc\u2010interval\u2010prolongation\u2010and\u2010proarrhythmic\u2010potential\u2010non\u2010antiarrhythmic\u20101> (2017). Accessed April 6 2020."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/53.2.481"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.573477"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201510610"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12928","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12928","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12928","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T18:25:40Z","timestamp":1693592740000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,19]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/cts.12928"],"URL":"https:\/\/doi.org\/10.1111\/cts.12928","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"type":"print","value":"1752-8054"},{"type":"electronic","value":"1752-8062"}],"subject":[],"published":{"date-parts":[[2020,12,19]]},"assertion":[{"value":"2020-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}