{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:57:02Z","timestamp":1791489422749,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,11,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>LMB\u2010100 is an antibody\u2010toxin conjugate with an antimesothelin Fab linked to a 24\u2010kilodalton portion of <jats:italic>Pseudomonas<\/jats:italic> exotoxin A with mutations that decrease immunogenicity. The objective of the current first\u2010in\u2010human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cohorts of 1 to 7 patients received intravenous LMB\u2010100 at 7 dose levels from 40 \u00b5g\/kg to 250 \u00b5g\/kg intravenously on days 1, 3, and 5 of a 21\u2010day cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 25 patients accrued, 17 had mesothelioma, 3 each had ovarian or pancreatic cancer, and 2 patients had gastric cancer. Dose\u2010limiting toxicities occurred in 2 of 4 patients treated at a dose of 250 \u00b5g\/kg (capillary leak syndrome) and in 3 of 7 patients treated at a dose of 170 \u00b5g\/kg (creatinine increase). The MTD of LMB\u2010100 was 140 \u00b5g\/kg. Of the 10 patients with mesothelioma who were treated at doses of 170 \u00b5g\/kg or 140 \u00b5g\/kg, 8 had stable disease and 2 developed progressive disease. Peak LMB\u2010100 plasma concentrations were dose\u2010dependent during cycle 1. The development of antidrug antibodies decreased LMB\u2010100 blood levels in 8 of 21 patients (38%) who received cycle 2 and 9 of 11 patients (81.8%) who received cycle 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The MTD for single\u2010agent LMB\u2010100 was found to be 140 \u00b5g\/kg given on a schedule of every other day for 3 doses every 3 weeks. Although less immunogenic than the first\u2010generation antimesothelin immunotoxin SS1P, the majority of patients developed antidrug antibodies after 2 cycles, indicating that LMB\u2010100 has limited antitumor efficacy as a single agent. Phase 2 studies of LMB\u2010100 plus pembrolizumab currently are ongoing for patients with mesothelioma and lung cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>Mesothelin, a cell surface antigen, is an attractive target for cancer therapy given its limited expression in normal human tissues and high expression in many human cancers. LMB\u2010100 is a recombinant antimesothelin immunotoxin consisting of a humanized antimesothelin antibody fragment fused to a truncated <jats:italic>Pseudomonas<\/jats:italic> exotoxin A.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>In the current study, the authors determined the safety, maximum tolerated dose, and pharmacokinetics of LMB\u2010100, as well as the generation of antidrug antibodies.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Ongoing phase 2 clinical trials are evaluating the combination of LMB\u2010100 plus pembrolizumab in patients with treatment\u2010refractory mesothelioma and non\u2013small cell lung cancer.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33145","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T16:09:37Z","timestamp":1598976577000},"page":"4936-4947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Phase 1 study of the immunotoxin LMB\u2010100 in patients with mesothelioma and other solid tumors expressing mesothelin"],"prefix":"10.1002","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4012-3633","authenticated-orcid":false,"given":"Raffit","family":"Hassan","sequence":"first","affiliation":[{"name":"Thoracic and GI Malignancies Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Alewine","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular 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