Cited 5 times in
Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
DC Field | Value | Language |
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dc.contributor.author | 라선영 | - |
dc.date.accessioned | 2023-11-07T07:49:18Z | - |
dc.date.available | 2023-11-07T07:49:18Z | - |
dc.date.issued | 2023-10 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/196525 | - |
dc.description.abstract | PF-06804103 is an anti-HER2 antibody-drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast and gastric cancers. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15-5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLT) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). Ninety-three patients enrolled in P1 (n = 47: HER2+ gastric cancer = 22, HER2+ breast cancer = 25) and P2 [n = 46: HER2+ breast cancer = 19, hormone receptor (HR)+ HER2-low breast cancer = 27] received PF-06804103. Four patients (3.0- and 4.0-mg/kg groups, n = 2 each) had DLTs (mostly Grade 3). Safety and efficacy results showed a dose-response relationship. Adverse events (AE) leading to treatment discontinuation (44/93, 47.3%) included neuropathy (11/93, 11.8%), skin toxicity (9/93, 9.7%), myalgia (5/93, 5.4%), keratitis (3/93, 3.2%), and arthralgia (2/93, 2.2%). Two (2/79, 2.5%) patients (P1, 4.0- and 5.0-mg/kg groups, n = 1 each) achieved complete response; 21 (21/79, 26.6%) achieved partial response. In P2, ORR was higher in HER2+ compared with HR+ HER2-low breast cancer [3.0 mg/kg: 16.7% (2/12) vs. 10.0% (1/10); 4.0 mg/kg: 47.4% (9/19) vs. 27.3% (3/11)]. PF-06804103 demonstrated antitumor activity; however, AEs led to discontinuation in 47.3% of patients. Safety and efficacy were dose-dependent. ©2023 The Authors; Published by the American Association for Cancer Research. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | MOLECULAR CANCER THERAPEUTICS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Antineoplastic Agents* / adverse effects | - |
dc.subject.MESH | Breast Neoplasms* / drug therapy | - |
dc.subject.MESH | Breast Neoplasms* / genetics | - |
dc.subject.MESH | Breast Neoplasms* / pathology | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunoconjugates* / adverse effects | - |
dc.subject.MESH | Receptor, ErbB-2 | - |
dc.subject.MESH | Stomach Neoplasms* / drug therapy | - |
dc.title | Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation 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 | Emiliano Calvo | - |
dc.contributor.googleauthor | Keun Seok Lee | - |
dc.contributor.googleauthor | Victor Moreno | - |
dc.contributor.googleauthor | Yeon Hee Park | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Pavani Chalasani | - |
dc.contributor.googleauthor | Wei Zhong | - |
dc.contributor.googleauthor | Li Zhou | - |
dc.contributor.googleauthor | Steven Pirie-Shepherd | - |
dc.contributor.googleauthor | Abraham C F Leung | - |
dc.contributor.googleauthor | Giuseppe Curigliano | - |
dc.identifier.doi | 10.1158/1535-7163.mct-23-0101 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J02254 | - |
dc.identifier.eissn | 1538-8514 | - |
dc.identifier.pmid | 37420274 | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.affiliatedAuthor | 라선영 | - |
dc.citation.volume | 22 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1191 | - |
dc.citation.endPage | 1203 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER THERAPEUTICS, Vol.22(10) : 1191-1203, 2023-10 | - |
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