Phase I results of S49076 plus gefitinib in patients with EGFR TKI-resistant non-small cell lung cancer harbouring MET/AXL dysregulation

doi:10.1016/j.lungcan.2021.03.012

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24104

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24104

Title:	Phase I results of S49076 plus gefitinib in patients with EGFR TKI-resistant non-small cell lung cancer harbouring MET/AXL dysregulation
Authors:	Park, K;Chang, GC;Curigliano, G;Lim, WT;Soo, RA;Molina-Vila, MA;Cattan, V;Darville, H;Gandossi, E;Smutna, V;Sudey, I;Viteri, S
Keywords:	Tyrosine kinase inhibitors;Epidermal growth factor receptor;Non-small cell lung cancer;Gefitinib;MET;AXL
Date:	2021
Issue Date:	2022-08-05T09:47:53Z (UTC)
Publisher:	ELSEVIER IRELAND LTD
ISSN:	0169-5002
Abstract:	Background: MET and AXL dysregulation is reported as a bypass mechanism driving tumour progression in nonsmall cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This non-comparative phase I study investigated the combination of gefitinib with S49076, a MET/AXL inhibitor, in advanced EGFR TKI-resistant NSCLC patients with MET and/or AXL dysregulation. Methods: Patients received S49076 at escalating doses of 500 or 600 mg with a fixed dose of 250 mg gefitinib orally once daily in continuous 28day cycles. MET and AXL dysregulation and EGFR/T790M mutation status were centrally assessed in tumour biopsies at screening. Tumour response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). EGFR TKI resistance mechanisms were analysed by next-generation sequencing. The clonal evolution of tumours was monitored with the analysis of circulating tumour DNA. Results: Of 92 pre-screened patients, 22 met the molecular inclusion criteria and 14 were included. The recommended dose was 600 mg daily S49076. Best overall responses were 2 partial responses (1 patient with MET dysregulation only, 1 MET and AXL co-dysregulation) and 8 patients with stable disease. Other potential concomitant mechanisms of resistance to EGFR TKI were identified in more than half of the included patients. Conclusions: S49076 plus gefitinib demonstrated a good tolerability with limited anti-tumour activity. Due to the low number of eligible patients, no tendency in term of activity appeared in any specific molecular subset and the data did not allow for identification of AXL overexpression as an oncogenic driver.
URI:	http://dx.doi.org/10.1016/j.lungcan.2021.03.012 https://www.webofscience.com/wos/woscc/full-record/WOS:000644431300017 https://ir.csmu.edu.tw:8080/handle/310902500/24104
Relation:	LUNG CANCER ,2021,v155 , P127-135
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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