{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:21:54Z","timestamp":1784762514859,"version":"3.55.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T00:00:00Z","timestamp":1573862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T00:00:00Z","timestamp":1573862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1007\/s10637-019-00869-2","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T20:01:22Z","timestamp":1573934482000},"page":"1156-1165","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors"],"prefix":"10.1007","volume":"38","author":[{"given":"Albiruni R.","family":"Abdul Razak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Wilson H.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey L.","family":"Uy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Blotner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Gore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,16]]},"reference":[{"issue":"1","key":"869_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.molmed.2006.11.002","volume":"13","author":"LT Vassilev","year":"2007","unstructured":"Vassilev LT (2007) MDM2 inhibitors for cancer therapy. Trends Mol Med 13(1):23\u201331","journal-title":"Trends Mol Med"},{"issue":"14","key":"869_CR2","doi-asserted-by":"publisher","first-page":"5979","DOI":"10.1021\/jm400487c","volume":"56","author":"Q Ding","year":"2013","unstructured":"Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B (2013) Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J Med Chem 56(14):5979\u20135983","journal-title":"J Med Chem"},{"issue":"5659","key":"869_CR3","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1126\/science.1092472","volume":"303","author":"LT Vassilev","year":"2004","unstructured":"Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303(5659):844\u2013848","journal-title":"Science"},{"issue":"21","key":"869_CR4","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1182\/blood.V124.21.116.116","volume":"124","author":"K Yee","year":"2014","unstructured":"Yee K, Martinelli G, Vey N, Dickinson MJ, Seiter K, Assouline S, Drummond M, Yoon S-S, Kasner M, Lee J-H, Kelly KR, Blotner S, Higgins B, Middleton S, Nichols G, Chen G, Zhong H, Pierceall WE, Zhi J, Chen L-C (2014) Phase 1\/1b study of RG7388, a potent MDM2 antagonist, in acute myelogenous leukemia (AML) patients (Pts) [abstract]. Blood 124(21):116","journal-title":"Blood"},{"key":"869_CR5","doi-asserted-by":"crossref","unstructured":"Siu LL, Italiano AI, Miller WH, Blay J-Y, Gietema JA, Bang Y-J, Mileshkin LR, Hirte HW, Reckner M, Higgins B, Jukofsky L, Blotner S, Zhi J, Middleton S, Nichols GL, Chen LC (2014) Phase 1 dose escalation, food effect, and biomarker study of RG7388, a more potent second-generation MDM2 antagonist, in patients (pts) with solid tumors [abstract]. J Clin Oncol 32(15 suppl):abstract 2535","DOI":"10.1200\/jco.2014.32.15_suppl.2535"},{"key":"869_CR6","doi-asserted-by":"crossref","unstructured":"Higgins B, Tovar C, Glen K, Railkar A, Filipovic Z, Qureshi F, Vu B, Ehrlich G, Fishlock D, Chen L-C, Middleton S, Nichols G, Packman K, Vassilev L (2014) Preclinical activity of MDM2 antagonist RO6839921, a pegylated prodrug for intravenous administration [abstract]. Mol Cancer Ther 14(12 suppl 2):abstract 156","DOI":"10.1158\/1535-7163.TARG-15-A156"},{"key":"869_CR7","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1016\/S0959-8049(16)32645-4","volume":"69","author":"A Razak","year":"2016","unstructured":"Razak A, Gore L, Britten CD, Miller WH, Uy GL, Nichols G, Middleton S, Blotner S, Zhi J, Jukofsky L, Pierceall W, Higgins B, Chen LC (2016) A phase I study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, for intravenous (IV) administration in patients with advanced solid tumors. Eur J Cancer 69:S21\u2013S22","journal-title":"Eur J Cancer"},{"issue":"1","key":"869_CR8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2307\/2531628","volume":"46","author":"J O'Quigley","year":"1990","unstructured":"O'Quigley J, Pepe M, Fisher L (1990) Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics 46(1):33\u201348","journal-title":"Biometrics"},{"key":"869_CR9","unstructured":"Yang H, Filipovic Z, Brown D, Breit SN, Vassilev LT (2003) Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activation. Mol Cancer Ther 2(10):1023\u20131029"},{"key":"869_CR10","doi-asserted-by":"crossref","unstructured":"Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL, Bui BN (2012) Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol 13(11):1133\u20131140","DOI":"10.1016\/S1470-2045(12)70474-6"},{"key":"869_CR11","doi-asserted-by":"crossref","unstructured":"Andreeff M, Kelly KR, Yee K, Assouline S, Strair R, Popplewell L, Bowen D, Martinelli G, Drummond MW, Vyas P, Kirschbaum M, Iyer SP, Ruvolo V, Gonz\u00e1lez GM, Huang X, Chen G, Graves B, Blotner S, Bridge P, Jukofsky L, Middleton S, Reckner M, Rueger R, Zhi J, Nichols G, Kojima K (2016) Results of the phase i trial of RG7112, a small-molecule MDM2 antagonist in leukemia. Clin Cancer Res 22(4):868\u2013876","DOI":"10.1158\/1078-0432.CCR-15-0481"},{"key":"869_CR12","doi-asserted-by":"crossref","unstructured":"Montesinos P, Esteve J, Konopleva M, Martinelli G, Ottmann O, Rodriguez-Veiga R, R\u00f6llig C, Wei A, Vey N, Chiu I, Monnet A, Ott MG, Fenaux P (2019) MIRROS: an ongoing randomized phase 3 trial of idasanutlin + ARA-C in patients with relapsed or refractory acute myeloid leukemia [abstract]. J Clin Oncol 37(15 suppl):abstract TPS7063","DOI":"10.1200\/JCO.2019.37.15_suppl.TPS7063"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-019-00869-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-019-00869-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-019-00869-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T04:41:49Z","timestamp":1678509709000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-019-00869-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,16]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["869"],"URL":"https:\/\/doi.org\/10.1007\/s10637-019-00869-2","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,16]]},"assertion":[{"value":"23 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors report support of the parent study and funding of editorial support from F. Hoffmann-La Roche. SB, A-MY, BH, and L-CC are employees of Roche. ARR has received research funding from Genentech\/Roche. WHM has served as a consultant for Amgen, BMS, GSK, Merck, Novartis and Roche; has received research funding to his institution from Amgen, AstraZeneca, BMS, MedImmune, Merck, MethylGene, Novartis, Pfizer and Roche; and has received honoraria from BMS, GSK, Merck, Novartis and Roche. LG has served as a consultant for Amgen, Genentech\/Roche and Novartis; has stock with Amgen, Anchiano, Blueprint Medicines, Celgene, Clovis, Mirati and Sanofi; and has a spouse employed with Anchiano.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}