Cited 57 times in
Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody
DC Field | Value | Language |
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dc.contributor.author | 홍민희 | - |
dc.date.accessioned | 2021-09-29T02:24:12Z | - |
dc.date.available | 2021-09-29T02:24:12Z | - |
dc.date.issued | 2021-04 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/184870 | - |
dc.description.abstract | Purpose: T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) blunts anticancer immunity and mediates resistance to programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors. We assessed a novel, first-in-class, TIM-3 mAb, LY3321367, alone or in combination with the anti-PD-L1 antibody, LY300054 in patients with advanced solid tumor. Patients and methods: This open-label, multicenter, phase Ia/b study aimed to define the safety/tolerability and recommended phase II dose (RP2D) of LY3321367 with or without LY300054. Secondary objectives included pharmacokinetics/pharmacodynamics, immunogenicity, and efficacy. Biomarkers were assessed in exploratory analysis. Results: No dose-limiting toxicities were observed in the monotherapy (N = 30) or combination (N = 28) dose escalation. LY3321367 treatment-related adverse events (≥2 patients) included pruritus, rash, fatigue, anorexia, and infusion-related reactions. Dose-proportional increase in LY3321367 concentrations was not affected by either LY300054 or antidrug antibodies (observed in 50%-70% of patients). Pharmacokinetic/pharmacodynamic modeling indicated 100% target engagement at doses ≥600 mg. LY3321367 RP2D was 1,200 mg biweekly for four doses followed by 600 mg every 2 weeks thereafter. In the non-small cell lung cancer monotherapy expansion cohort, outcomes varied by prior anti-PD-1 therapy response status: anti-PD-1/L1 refractory patients [N = 23, objective response rate (ORR) 0%, disease control rate (DCR) 35%, progression-free survival (PFS) 1.9 months] versus anti-PD-1/L1 responders (N = 14, ORR 7%, DCR 50%, PFS 7.3 months). In combination expansion cohorts (N = 91), ORR and DCR were 4% and 42%; CD8 infiltration in paired biopsies increased in approximately half these patients. Conclusions: LY3321367 exhibited acceptable safety profile with favorable pharmacokinetics/pharmacodynamics but only modest antitumor activity. The therapeutic relevance of TIM-3 blockade requires further investigation. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | James J Harding | - |
dc.contributor.googleauthor | Victor Moreno | - |
dc.contributor.googleauthor | Yung-Jue Bang | - |
dc.contributor.googleauthor | Min Hee Hong | - |
dc.contributor.googleauthor | Amita Patnaik | - |
dc.contributor.googleauthor | José Trigo | - |
dc.contributor.googleauthor | Anna M Szpurka | - |
dc.contributor.googleauthor | Noboru Yamamoto | - |
dc.contributor.googleauthor | Toshihiko Doi | - |
dc.contributor.googleauthor | Siqing Fu | - |
dc.contributor.googleauthor | Boris Calderon | - |
dc.contributor.googleauthor | Nieves Velez de Mendizabal | - |
dc.contributor.googleauthor | Emiliano Calvo | - |
dc.contributor.googleauthor | Danni Yu | - |
dc.contributor.googleauthor | Leena Gandhi | - |
dc.contributor.googleauthor | Zhuqing Tina Liu | - |
dc.contributor.googleauthor | Violeta Regnier Galvao | - |
dc.contributor.googleauthor | Ching Ching Leow | - |
dc.contributor.googleauthor | Maria J de Miguel | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-20-4405 | - |
dc.contributor.localId | A04393 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 33514524 | - |
dc.identifier.url | https://clincancerres.aacrjournals.org/content/27/8/2168.long | - |
dc.contributor.alternativeName | Hong, Min Hee | - |
dc.contributor.affiliatedAuthor | 홍민희 | - |
dc.citation.volume | 27 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 2168 | - |
dc.citation.endPage | 2178 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.27(8) : 2168-2178, 2021-04 | - |
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