{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:46:19Z","timestamp":1791053179950,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> MDX-210 is a bispecific antibody that binds simultaneously to type I Fc receptors for immunoglobulin G (IgG) (Fc gamma RI) and to the HER-2\/neu oncogene protein product. MDX-210 effectively directs Fc gamma RI-positive effector cells such as monocytes and macrophages to phagocytose or kill tumor cells that overexpress HER-2\/neu. The goals of this phase Ia\/Ib trial were to determine the maximum-tolerated dose (MTD) and\/or the optimal biologic dose (OBD) of MDX-210. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Patients with advanced breast or ovarian cancer that overexpressed HER-2\/neu were eligible for treatment. Cohorts of three patients received a single intravenous (IV) infusion of MDX-210 at increasing dose levels from 0.35 to 10.0 mg\/m2. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Treatment was well tolerated, with most patients experiencing transient grade 1 to 2 fevers, malaise, and hypotension only. Two patients experienced transient grade 3 hypotension at 10.0 mg\/m2. Transient monocytopenia and lymphopenia developed at 1 to 2 hours, but no other hematologic changes were observed. Doses of MDX-210 &gt; or = 3.5 mg\/m2 saturated &gt; or = 80% of monocyte Fc gamma RI and produced peak plasma concentrations &gt; or = 1 microgram\/mL, which is greater than the concentration for optimal monocyte\/macrophage activation in vitro. Elevated plasma levels of the monocyte products tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and neopterin were observed with maximal levels at doses &gt; or = 7.0 mg\/m2. Localization of MDX-210 in tumor tissue was demonstrated in two patients. One partial and one mixed tumor response were observed among 10 assessable patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> MDX-210 is immunologically active at well-tolerated doses. The MTD and OBD is 7 to 10 mg\/m2. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.1995.13.9.2281","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T13:03:36Z","timestamp":1487855016000},"page":"2281-2292","source":"Crossref","is-referenced-by-count":140,"title":["Phase Ia\/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2\/neu."],"prefix":"10.1200","volume":"13","author":[{"given":"F H","family":"Valone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P M","family":"Guyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L D","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Memoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Deo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mrozek-Orlowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1995.13.9.2281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T19:55:21Z","timestamp":1653508521000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1995.13.9.2281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,9]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1995,9]]}},"alternative-id":["10.1200\/JCO.1995.13.9.2281"],"URL":"https:\/\/doi.org\/10.1200\/jco.1995.13.9.2281","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,9]]}}}