Detailed Information

Cited 100 time in webofscience Cited 104 time in scopus
Metadata Downloads

Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study

Authors
Ahn, Myung-JuHan, Ji-YounLee, Ki HyeongKim, Sang-WeKim, Dong-WanLee, Yun-GyooCho, Eun KyungKim, Joo-HangLee, Gyeong-WonLee, Jong-SeokMin, Young JooKim, Jin-SooLee, Sung SookKim, Hye RyunHong, Min HeeAhn, Jin SeokSun, Jong-MuKim, Heung TaeLee, Dae HoKim, SoheeCho, Byoung Chul
Issue Date
Dec-2019
Publisher
ELSEVIER SCIENCE INC
Citation
LANCET ONCOLOGY, v.20, no.12, pp 1681 - 1690
Pages
10
Indexed
SCIE
SCOPUS
Journal Title
LANCET ONCOLOGY
Volume
20
Number
12
Start Page
1681
End Page
1690
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/8468
DOI
10.1016/S1470-2045(19)30504-2
ISSN
1470-2045
1474-5488
Abstract
Background Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) given EGFR tyrosine kinase inhibitors (TKIs) inevitably become resistant to first-generation or second-generation drugs. We assessed the safety, tolerability, pharmacokinetics, and activity of lazertinib-an irreversible, third-generation, mutant-selective, EGFR TKI-in patients with advanced NSCLC progressing after EGFR TKI therapy. Methods This first-in-human, open-label, multicentre, phase 1-2 study had three parts: dose escalation, dose expansion, and dose extension; here, we report results on dose escalation and dose expansion. The study was done in 14 hospitals in Korea. Eligible patients were aged 20 years or older and had advanced NSCLC harbouring an activating EGFR mutation and progressing after first-generation or second-generation EGFR TKI treatment, a defined tumour T790M mutation status, an Eastern Cooperative Oncology Group performance status of 0-1, at least one measurable extracranial lesion, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and adequate organ function. Patients were enrolled to seven dose-escalation cohorts according to a rolling six design; five cohorts were expanded. Patients were given oral lazertinib 20 mg, 40 mg, 80 mg, 120 mg, 160 mg, 240 mg, or 320 mg once daily continuously in 21-day cycles. Primary endpoints were safety and tolerability and secondary endpoints included objective response in evaluable patients. This study is registered with ClinicalTrials.gov, NCT03046992, and the phase 2 extension study is ongoing. Findings Between Feb 15, 2017, and May 28, 2018, 127 patients were enrolled into the dose escalation group (n=38) and dose expansion group (n=89). No dose-limiting toxicities occurred. There was no dose-dependent increase in adverse events. The most commonly reported adverse events were grade 1-2 rash or acne (in 38 [30%] of 127 patients) and pruritus (in 34 [27%]). Grade 3 or grade 4 adverse events occurred in 20 (16%) patients, with the most common being grade 3 pneumonia (four [3%]). Treatment-related grade 3 or 4 adverse events occurred in four (3%) patients; treatment-related serious adverse events were reported in six patients (5%). There were no adverse events with an outcome of death and no treatment-related deaths. The proportion of patients achieving an objective response by independent central review assessment was 69 (54%; 95% CI 46-63) of 127. Interpretation Lazertinib had a tolerable safety profile and showed promosing clinical activity in patients with NSCLC progressing on or after EGFR TKI therapy. Our findings provide a rationale for further clinical investigations. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Medicine > Department of Medicine > Journal Articles

qrcode

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

Related Researcher

Researcher Lee, Gyeong Won photo

Lee, Gyeong Won
의과대학 (의학과)
Read more

Altmetrics

Total Views & Downloads

BROWSE