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We aimed to study tumor HER2 expression and its effects on T\u2010DM1 responses in patients with HER2\u2010positive urothelial bladder cancer (UBC) or pancreatic cancer (PC)\/cholangiocarcinoma (CC). In the phase II KAMELEON study (NCT02999672), HER2 status was centrally assessed by immunohistochemistry, with positivity defined as non\u2010focal homogeneous or heterogeneous overexpression of HER2 in \u226530% of stained cells. We also performed exploratory biomarker analyses (e.g., gene\u2010protein assay) on tissue samples collected from study participants and consenting patients who failed screening. Of the 284 patients successfully screened for HER2 status (UBC, <jats:italic>n<\/jats:italic>\u2009=\u200969; PC\/CC, <jats:italic>n<\/jats:italic>\u2009=\u2009215), 13 with UBC, four with PC, and three with CC fulfilled eligibility criteria. Due to recruitment difficulty, the sponsor terminated KAMELEON prematurely. Of the five responders in the UBC cohort (overall response rate, 38.5%), HER2 expression was heterogeneous in two and homogeneous in three. The one responder in the PC\/CC cohort had PC, and the tumor displayed homogeneous expression. In the biomarker\u2010evaluable population, composed of screen\u2010failed and enrolled patients, 24.3% (9\/37), 1.5% (1\/66), and 8.2% (4\/49) of those with UBC, PC, or CC, respectively, had HER2\u2010positive tumors. In a gene\u2010protein assay combining in situ hybridization with immunohistochemistry, greater HER2 homogeneity was associated with increased <jats:italic>ERBB2<\/jats:italic> amplification ratio. In conclusion, KAMELEON showed that some patients with HER2\u2010positive UBC or PC can respond to T\u2010DM1 and provided insight into the prevalence of HER2 positivity and expression patterns in three non\u2010breast tumor types.<\/jats:p>","DOI":"10.1002\/cam4.5893","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T19:04:19Z","timestamp":1682795059000},"page":"12071-12083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Phase <scp>II<\/scp> study (<scp>KAMELEON<\/scp>) of single\u2010agent <scp>T\u2010DM1<\/scp> in patients with <scp>HER2<\/scp>\u2010positive advanced urothelial bladder cancer or pancreatic cancer\/cholangiocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-7425","authenticated-orcid":false,"given":"Elisabeth G. 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All rights reserved. Accessed January 7 2022. To view the most recent and complete version of the guideline go online toNCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content use or application and disclaims any responsibility for their application or use in any way."},{"key":"e_1_2_9_27_1","unstructured":"Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) for Head and Neck Cancers Guidelines V.1.2022. \u00a9 National Comprehensive Cancer Network Inc. 2022. All rights reserved. Accessed January 7 2022. To view the most recent and complete version of the guideline go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content use or application and disclaims any responsibility for their application or use in any way."},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"issue":"10","key":"e_1_2_9_29_1","first-page":"2199","article-title":"Heterogeneity of erbB\u20102 gene amplification in bladder cancer","volume":"53","author":"Sauter G","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp488"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-017-4453-8"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-7-60"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3443-1"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5687-0"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-018-00923-7"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.36"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12375"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1557"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1464-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i15.1964"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.10.018"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24265"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-014-0402-y"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1781-0"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2093-6"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2659"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-021-00252-6"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.422"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2011.05.035"},{"issue":"8","key":"e_1_2_9_50_1","first-page":"2440","article-title":"Her\u20102\/neu overexpression in muscle\u2010invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors","volume":"7","author":"Jimenez RE","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0152"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-021-09814-1"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1014"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:47:26Z","timestamp":1697071646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.5893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,29]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/cam4.5893"],"URL":"https:\/\/doi.org\/10.1002\/cam4.5893","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,29]]},"assertion":[{"value":"2022-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}