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Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study
DC Field | Value | Language |
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dc.contributor.author | 라선영 | - |
dc.date.accessioned | 2023-03-10T01:14:00Z | - |
dc.date.available | 2023-03-10T01:14:00Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 1470-2045 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193075 | - |
dc.description.abstract | Background: HER2-targeted therapies have substantially improved outcomes for patients with HER2-positive breast and gastric or gastro-oesophageal junction cancers. Several other cancers exhibit HER2 expression or amplification, suggesting that HER2-targeted agents can have broader therapeutic impact. Zanidatamab is a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2. The aim of this study was to evaluate the safety and anti-tumour activity of zanidatamab across a range of solid tumours with HER2 expression or amplification. Methods: This first-in-human, multicentre, phase 1, dose-escalation and expansion trial included patients aged 18 years and older, with a life expectancy of at least 3 months, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and locally advanced or metastatic, HER2-expressing or HER2-amplified solid tumours of any kind who had received all available approved therapies. The primary objectives of part 1 were to identify the maximum tolerated dose, optimal biological dose, or recommended dose of zanidatamab; all patients were included in the primary analyses. Part 1 followed a 3 + 3 dose-escalation design, including different intravenous doses (from 5 mg/kg to 30 mg/kg) and intervals (every 1, 2, or 3 weeks). The primary objective of part 2 was to evaluate the safety and tolerability of zanidatamab monotherapy in solid tumours. This trial is registered with ClinicalTrials.gov (NCT02892123), and parts 1 and 2 of the trial are complete. Part 3 of the study evaluates the use of zanidatamab in combination with chemotherapy and is ongoing. Findings: Recruitment took place between Sept 1, 2016, and March 13, 2021. In Part 1 (n=46), no dose-limiting toxicities were detected and the maximum tolerated dose was not reached. The recommended dose for part 2 (n=22 for biliary tract cancer; n=28 for colorectal cancer; and n=36 for other HER2-expressing or HER2-amplified cancers excluding breast or gastro-oesophageal cancers; total n=86) was 20 mg/kg every 2 weeks. The most frequent treatment-related adverse events in part 1 of the study were diarrhoea (24 [52%] of 46 patients; all grade 1-2) and infusion reactions (20 [43%] of 46 patients; all grade 1-2). The most frequent treatment-related adverse events in part 2 of the study were diarrhoea (37 [43%] of 86 patients; all grade 1-2 except for one patient) and infusion reactions (29 [34%] of 86 patients; all grade 1-2). A total of six grade 3 treatment-related adverse events were reported in four (3%) of 132 patients. In part 2, 31 (37%; 95% CI 27·0-48·7) of 83 evaluable patients had a confirmed objective response. There were no treatment-related deaths. Interpretation: These results support that HER2 is an actionable target in various cancer histologies, including biliary tract cancer and colorectal cancer. Evaluation of zanidatamab continues in ongoing studies. Funding: Zymeworks. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Lancet Pub. Group | - |
dc.relation.isPartOf | LANCET ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antibodies, Bispecific* | - |
dc.subject.MESH | Antineoplastic Agents* | - |
dc.subject.MESH | Colorectal Neoplasms* | - |
dc.subject.MESH | Diarrhea | - |
dc.subject.MESH | Esophageal Neoplasms* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lymphoma, Follicular* | - |
dc.subject.MESH | Stomach Neoplasms* / drug therapy | - |
dc.subject.MESH | Stomach Neoplasms* / genetics | - |
dc.title | Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Funda Meric-Bernstam | - |
dc.contributor.googleauthor | Muralidhar Beeram | - |
dc.contributor.googleauthor | Erika Hamilton | - |
dc.contributor.googleauthor | Do-Youn Oh | - |
dc.contributor.googleauthor | Diana L Hanna | - |
dc.contributor.googleauthor | Yoon-Koo Kang | - |
dc.contributor.googleauthor | Elena Elimova | - |
dc.contributor.googleauthor | Jorge Chaves | - |
dc.contributor.googleauthor | Rachel Goodwin | - |
dc.contributor.googleauthor | Jeeyun Lee | - |
dc.contributor.googleauthor | Lisle Nabell | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Jose Mayordomo | - |
dc.contributor.googleauthor | Anthony El-Khoueiry | - |
dc.contributor.googleauthor | Shubham Pant | - |
dc.contributor.googleauthor | Kanwal Raghav | - |
dc.contributor.googleauthor | Jin Won Kim | - |
dc.contributor.googleauthor | Amita Patnaik | - |
dc.contributor.googleauthor | Todd Gray | - |
dc.contributor.googleauthor | Rupert Davies | - |
dc.contributor.googleauthor | Mark A Ozog | - |
dc.contributor.googleauthor | Joseph Woolery | - |
dc.contributor.googleauthor | Keun-Wook Lee | - |
dc.identifier.doi | 10.1016/S1470-2045(22)00621-0 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J02154 | - |
dc.identifier.eissn | 1474-5488 | - |
dc.identifier.pmid | 36400106 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1470204522006210 | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.affiliatedAuthor | 라선영 | - |
dc.citation.volume | 23 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1558 | - |
dc.citation.endPage | 1570 | - |
dc.identifier.bibliographicCitation | LANCET ONCOLOGY, Vol.23(12) : 1558-1570, 2022-12 | - |
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