{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T23:09:25Z","timestamp":1783465765470,"version":"3.55.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,2,17]],"date-time":"2018-02-17T00:00:00Z","timestamp":1518825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,2,17]],"date-time":"2018-02-17T00:00:00Z","timestamp":1518825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019203","name":"ImmunoGen Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019203","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n          <jats:p><jats:italic>Background<\/jats:italic> CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. <jats:italic>Methods<\/jats:italic> This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity. IMGN529 was administered intravenously once every 3\u00a0weeks, and dosed using a conventional 3\u2009+\u20093 dose-escalation design. <jats:italic>Results<\/jats:italic> Forty-nine patients were treated at doses escalating from 0.1 to 1.8\u00a0mg\/kg. Dose limiting toxicities occurred in eight patients and included peripheral neuropathy, febrile neutropenia, neutropenia, and thrombocytopenia. The most frequent treatment-emergent adverse events were fatigue (39%), neutropenia, pyrexia, and thrombocytopenia (each 37%). Adverse events led to treatment discontinuation in 10 patients (20%). Eight patients (16%) had treatment-related serious adverse events, the most common being grade 3 febrile neutropenia. The MTD (with growth factor support) was 1.4\u00a0mg\/kg every 3\u00a0weeks. IMGN529 plasma exposure increased monotonically with dose and was consistent with target-mediated drug disposition. Five (13%) of 39 response-evaluable patients achieved an objective response (one complete response and four partial responses), four of which occurred in the subgroup of patients with diffuse large B-cell lymphoma. <jats:italic>Conclusions<\/jats:italic> The manageable safety profile of IMGN529 and preliminary evidence of activity, particularly in DLBCL patients, support the continued development of this novel CD37-targeting agent.<\/jats:p>","DOI":"10.1007\/s10637-018-0570-4","type":"journal-article","created":{"date-parts":[[2018,2,17]],"date-time":"2018-02-17T01:36:17Z","timestamp":1518831377000},"page":"869-876","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-7529","authenticated-orcid":false,"given":"Anastasios","family":"Stathis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian W.","family":"Flinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kami","family":"Maddocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Weitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Zucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela C.","family":"Munteanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lia Palomba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,17]]},"reference":[{"key":"570_CR1","doi-asserted-by":"publisher","first-page":"5019","DOI":"10.1182\/blood-2011-01-293050","volume":"117","author":"E Campo","year":"2011","unstructured":"Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (2011) The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. 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AS, IWF, SW and EZ report grant\/funding support from ImmunoGen to conduct the trial. All other authors declare no competing interests.","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":"Written informed consent was obtained from all participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}