0 55

Cited 0 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
dc.contributor.author홍민희-
dc.date.accessioned2021-09-29T02:24:12Z-
dc.date.available2021-09-29T02:24:12Z-
dc.date.issued2021-04-
dc.identifier.issn1078-0432-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184870-
dc.description.abstractPurpose: 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.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isPartOfCLINICAL CANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleBlocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorJames J Harding-
dc.contributor.googleauthorVictor Moreno-
dc.contributor.googleauthorYung-Jue Bang-
dc.contributor.googleauthorMin Hee Hong-
dc.contributor.googleauthorAmita Patnaik-
dc.contributor.googleauthorJosé Trigo-
dc.contributor.googleauthorAnna M Szpurka-
dc.contributor.googleauthorNoboru Yamamoto-
dc.contributor.googleauthorToshihiko Doi-
dc.contributor.googleauthorSiqing Fu-
dc.contributor.googleauthorBoris Calderon-
dc.contributor.googleauthorNieves Velez de Mendizabal-
dc.contributor.googleauthorEmiliano Calvo-
dc.contributor.googleauthorDanni Yu-
dc.contributor.googleauthorLeena Gandhi-
dc.contributor.googleauthorZhuqing Tina Liu-
dc.contributor.googleauthorVioleta Regnier Galvao-
dc.contributor.googleauthorChing Ching Leow-
dc.contributor.googleauthorMaria J de Miguel-
dc.identifier.doi10.1158/1078-0432.CCR-20-4405-
dc.contributor.localIdA04393-
dc.relation.journalcodeJ00564-
dc.identifier.pmid33514524-
dc.identifier.urlhttps://clincancerres.aacrjournals.org/content/27/8/2168.long-
dc.contributor.alternativeNameHong, Min Hee-
dc.contributor.affiliatedAuthor홍민희-
dc.citation.volume27-
dc.citation.number8-
dc.citation.startPage2168-
dc.citation.endPage2178-
dc.identifier.bibliographicCitationCLINICAL CANCER RESEARCH, Vol.27(8) : 2168-2178, 2021-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.