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A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer
DC Field | Value | Language |
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dc.contributor.author | Reynolds, Kerry Lynn | - |
dc.contributor.author | Bedard, Philippe L. | - |
dc.contributor.author | Lee, Se-Hoon | - |
dc.contributor.author | Lin, Chia-Chi | - |
dc.contributor.author | Tabernero, Josep | - |
dc.contributor.author | Alsina, Maria | - |
dc.contributor.author | Cohen, Ezra | - |
dc.contributor.author | Baselga, Jose | - |
dc.contributor.author | Blumenschein, George, Jr. | - |
dc.contributor.author | Graham, Donna M. | - |
dc.contributor.author | Garrido-Laguna, Ignacio | - |
dc.contributor.author | Juric, Dejan | - |
dc.contributor.author | Sharma, Sunil | - |
dc.contributor.author | Salgia, Ravi | - |
dc.contributor.author | Seroutou, Abdelkader | - |
dc.contributor.author | Tian, Xianbin | - |
dc.contributor.author | Fernandez, Rose | - |
dc.contributor.author | Morozov, Alex | - |
dc.contributor.author | Sheng, Qing | - |
dc.contributor.author | Ramkumar, Thiruvamoor | - |
dc.contributor.author | Zubel, Angela | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.date.accessioned | 2017-11-02T01:26:15Z | - |
dc.date.available | 2017-11-02T10:30:40Z | - |
dc.date.created | 2018-09-19 | - |
dc.date.issued | 2017-09 | - |
dc.identifier.citation | BMC Cancer, Vol.17, p. 646 | - |
dc.identifier.issn | 1471-2407 | - |
dc.identifier.other | 55249 | - |
dc.identifier.uri | https://hdl.handle.net/10371/138283 | - |
dc.description | ADA: anti-drug antibodies; AE: adverse event; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; AUC: area under curve; BLRM: Bayesian logistic regression model; CEER: Collaborative Enzyme Enhanced Reactive; CI: confidence interval; CT: computed tomography; DLT: dose-limiting toxicities; ECOG: Eastern Cooperative Oncology Group; EGFR: epidermal growth factor receptor; ErbB: v-erb-b2 erythroblastic leukemia viral oncogene homolog; ESCC: esophageal squamous cell carcinoma; EWOC: escalation with overdose control; EX: expansion phase; FAS: full analysis set; HER2: human epidermal growth factor receptor 2; HER3: human epidermal growth factor receptor; IgG1: immunoglobulin G1; IHC: immunohistochemistry; IRR: infusion-related reactions; IV: intravenously; MRI: magnetic resonance imaging; MTD: maximum tolerated dose; ND: not determined; NGS: nextgeneration sequencing; NRG1: neuregulin 1; ORR: overall response rate; p-AKT: phosphor-AKT; PD: progressive disease; PFS: progression-free survival; p-HER3: phospho-human epidermal growth factor receptor 3; PI3K: phosphoinositide 3-kinase; PIK3CA amp: PIK3CA amplified; PIK3CA: phosphoinositide 3-kinase, catalytic subunit alpha; PR: partial response; PS: performance status; PTEN: phosphatase and tensin homolog; Q2W: once every two weeks; QW: once weekly; RDE: recommended dose for expansion; RECIST: Response Evaluation Criteria in Solid Tumors; RTK: receptor tyrosine kinase; RT-PCR: reverse transcription polymerase chain reaction; SAE: serious adverse event; SCCHN: squamous cell carcinoma of the head and neck; SD: stable disease; t-AKT: total AKT; t-HER3: total human epidermal growth factor receptor 3; UNK: unknown | ko_KR |
dc.description.abstract | Background: Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. Methods: This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Results: Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [ both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting > 30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. Conclusions: LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. | - |
dc.language | 영어 | - |
dc.language.iso | en | ko_KR |
dc.publisher | BioMed Central | - |
dc.title | A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 방영주 | - |
dc.identifier.doi | 10.1186/s12885-017-3641-6 | - |
dc.citation.journaltitle | BMC Cancer | - |
dc.identifier.wosid | 000410579600003 | - |
dc.identifier.scopusid | 2-s2.0-85029370515 | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s). | - |
dc.date.updated | 2017-10-03T16:48:46Z | - |
dc.citation.startpage | 646 | - |
dc.citation.volume | 17 | - |
dc.identifier.sci | 000410579600003 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | AMERICAN-SOCIETY | - |
dc.subject.keywordPlus | SOLID TUMORS | - |
dc.subject.keywordPlus | TRASTUZUMAB | - |
dc.subject.keywordPlus | RECOMMENDATIONS | - |
dc.subject.keywordPlus | PERTUZUMAB | - |
dc.subject.keywordPlus | U3-1287 | - |
dc.subject.keywordPlus | TRIALS | - |
dc.subject.keywordPlus | ERBB3 | - |
dc.subject.keywordAuthor | Phase I | - |
dc.subject.keywordAuthor | HER3 | - |
dc.subject.keywordAuthor | HER2 | - |
dc.subject.keywordAuthor | Monoclonal antibody | - |
dc.subject.keywordAuthor | LJM716 | - |
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