Cited 0 times in

Phase II study investigating the efficacy and safety of glesatinib (MGCD265) in patients with advanced NSCLC containing MET activating alterations

Authors
 David S Hong  ;  Federico Cappuzzo  ;  Byoung Chul Cho  ;  Afshin Dowlati  ;  Maen Hussein  ;  Dong-Wan Kim  ;  Ivor Percent  ;  James G Christensen  ;  Josée Morin  ;  Diane Potvin  ;  Demiana Faltaos  ;  Vanessa Tassell  ;  Hirak Der-Torossian  ;  Richard Chao 
Citation
 LUNG CANCER, Vol.190 : 107512, 2024-04 
Journal Title
LUNG CANCER
ISSN
 0169-5002 
Issue Date
2024-04
MeSH
Benzeneacetamides* ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Carcinoma, Non-Small-Cell Lung* / pathology ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Mutation ; Protein Kinase Inhibitors / adverse effects ; Pyridines* ; Tablets / therapeutic use
Keywords
AXL ; Glesatinib ; MET amplification ; MET exon 14 ; MET mutation ; Non-small cell lung cancer
Abstract
Objectives: Dysregulated signaling by mesenchymal epithelial transition factor (MET) and heightened AXL activation are implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Glesatinib (MGCD265) is an investigational, oral inhibitor of MET and AXL. Materials and methods: This open-label, Phase II study investigated glesatinib (free-base suspension [FBS] capsule 1050 mg BID or spray-dried dispersion [SDD] tablet 750 mg BID) in patients with advanced, previously treated NSCLC across four cohorts grouped according to presence of MET activating mutations or amplification in tumor or ctDNA. The primary endpoint was objective response rate (ORR). Results: Sixty-eight patients were enrolled: n = 28 and n = 8 with MET exon 14 skipping mutations in tumor tissue and ctDNA, respectively, and n = 20 and n = 12 with MET gene amplification in tumor tissue and ctDNA, respectively. Overall, ORR was 11.8 %, median progression-free survival was 4.0 months, and median overall survival was 7.0 months. Among patients with MET activating mutations, ORR was 10.7 % with tumor testing and 25.0 % with ctDNA testing. For MET amplification, responses were observed only in patients enrolled by tumor testing (ORR 15.0 %). Diarrhea (82.4 %), nausea (50.0 %), increased alanine aminotransferase (41.2 %), fatigue (38.2 %), and increased aspartate aminotransferase (36.8 %) were the most frequent adverse events assessed as related to study medication. Glesatinib exposure was similar with the SDD tablet and FBS capsule formulations. The study was terminated early by the sponsor due to modest clinical activity. Conclusions: Glesatinib had an acceptable safety profile in patients with advanced, pre-treated NSCLC with MET activating alterations. Modest clinical activity was observed, which likely reflects suboptimal drug bioavailability suggested by previously reported Phase I data, and pharmacodynamic findings of lower than anticipated increases in circulating soluble shed MET ectodomain (s-MET).
Full Text
https://www.sciencedirect.com/science/article/pii/S016950022400045X
DOI
38417277
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/200579
사서에게 알리기
  feedback

qrcode

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

Browse

Links