Cited 12 times in
First-in-human study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors
DC Field | Value | Language |
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dc.contributor.author | 범승훈 | - |
dc.contributor.author | 정재호 | - |
dc.contributor.author | 김효송 | - |
dc.contributor.author | 라선영 | - |
dc.contributor.author | 김건민 | - |
dc.date.accessioned | 2022-12-22T04:47:09Z | - |
dc.date.available | 2022-12-22T04:47:09Z | - |
dc.date.issued | 2022-10 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/192217 | - |
dc.description.abstract | Preclinical models suggest anticancer activity of IM156, a novel biguanide mitochondrial protein complex 1 inhibitor of oxidative phosphorylation (OXPHOS). This first-in-human dose-escalation study enrolled patients with refractory advanced solid tumors to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Eligible patients received oral IM156 every other day (QOD) or daily (QD) and were assessed for safety, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary signals of efficacy. 22 patients with advanced cancers (gastric, n = 8; colorectal, n = 3; ovarian, n = 3; other, n = 8) received IM156 100 to 1,200 mg either QOD or QD. There were no DLTs. However, 1,200 mg QD was not well tolerated due to nausea; 800 mg QD was determined as the RP2D. The most frequent treatment-related AEs (TRAEs) were nausea (n = 15; 68%), diarrhea (n = 10; 46%), emesis (n = 9; 41%), fatigue (n = 4; 18%) and abdominal pain, constipation, and blood lactate increased (n = 2 each; 9%). Grade 3 nausea (n = 3; 14%) was the only grade ≥ 3 TRAE. Plasma exposures increased dose proportionally; mean Day 27 area under the curve (AUC<sub>0-24</sub>) values were higher following QD administration compared to the respective QOD regimen. Stable disease (SD), observed in 7 (32%) patients (confirmed in 2 [9%]), was the best response. To our knowledge, this is the first phase 1 study of an OXPHOS inhibitor that established a RP2D for further clinical development in cancer. Observed AEs of IM156 were manageable and SD was the best response. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Springer | - |
dc.relation.isPartOf | INVESTIGATIONAL NEW DRUGS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antineoplastic Agents* / adverse effects | - |
dc.subject.MESH | Biguanides / therapeutic use | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Maximum Tolerated Dose | - |
dc.subject.MESH | Nausea / chemically induced | - |
dc.subject.MESH | Neoplasms* / metabolism | - |
dc.subject.MESH | Oxidative Phosphorylation | - |
dc.title | First-in-human study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Filip Janku | - |
dc.contributor.googleauthor | Seung-Hoon Beom | - |
dc.contributor.googleauthor | Yong Wha Moon | - |
dc.contributor.googleauthor | Tae Won Kim | - |
dc.contributor.googleauthor | Young G Shin | - |
dc.contributor.googleauthor | Dong-Seok Yim | - |
dc.contributor.googleauthor | Gun Min Kim | - |
dc.contributor.googleauthor | Hyo Song Kim | - |
dc.contributor.googleauthor | Sun Young Kim | - |
dc.contributor.googleauthor | Jae-Ho Cheong | - |
dc.contributor.googleauthor | Young Woo Lee | - |
dc.contributor.googleauthor | Barb Geiger | - |
dc.contributor.googleauthor | Sanghee Yoo | - |
dc.contributor.googleauthor | Archie Thurston | - |
dc.contributor.googleauthor | Dean Welsch | - |
dc.contributor.googleauthor | Marc S Rudoltz | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.identifier.doi | 10.1007/s10637-022-01277-9 | - |
dc.contributor.localId | A04581 | - |
dc.contributor.localId | A03717 | - |
dc.contributor.localId | A01202 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J01184 | - |
dc.identifier.eissn | 1573-0646 | - |
dc.identifier.pmid | 35802288 | - |
dc.subject.keyword | Biguanide | - |
dc.subject.keyword | Cancer | - |
dc.subject.keyword | Clinical trial | - |
dc.subject.keyword | IM156 | - |
dc.subject.keyword | Protein complex I inhibitor | - |
dc.contributor.alternativeName | Beom, Seung Hoon | - |
dc.contributor.affiliatedAuthor | 범승훈 | - |
dc.contributor.affiliatedAuthor | 정재호 | - |
dc.contributor.affiliatedAuthor | 김효송 | - |
dc.contributor.affiliatedAuthor | 라선영 | - |
dc.citation.volume | 40 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1001 | - |
dc.citation.endPage | 1010 | - |
dc.identifier.bibliographicCitation | INVESTIGATIONAL NEW DRUGS, Vol.40(5) : 1001-1010, 2022-10 | - |
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