Phase I Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-positive EGFR-mutant Non–small Cell Lung Cancer
Journal
Clinical Cancer Research
Journal Volume
27
Journal Issue
4
Pages
992-1003
Date Issued
2021
Author(s)
Yu H.A.
Paz-Ares L.G.
Lee K.H.
Garrido P.
Park K.
Kim J.-H.
Lee D.H.
Mao H.
Wijayawardana S.R.
Gao L.
Hozak R.R.
Chao B.H.
Planchard D.
Abstract
PURPOSE: -mutant non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: T790M-positive NSCLC, who had progressed following EGFR TKI but were third-generation EGFR TKI-naïve. A dose-limiting toxicity (DLT) period with as-needed dose deescalation was followed by an expansion cohort. Patients received daily oral osimertinib and intravenous ramucirumab every 2 weeks until progression or discontinuation. RESULTS: = 15) had similar safety outcomes. Five patients remain on treatment. Objective response rate (ORR) was 76%. Median duration of response was 13.4 months [90% confidence interval (CI): 9.6-21.2]. Median progression-free survival (PFS) was 11.0 months (90% CI: 5.5-19.3). Efficacy was observed in patients with and without CNS metastasis (ORR 60% and 87%; median PFS 10.9 and 14.7 months, respectively). Exploratory biomarker analyses in circulating tumor DNA suggested that on-treatment loss of EGFR Exon 19 deletion or L858R mutations, detectable at baseline, correlated with longer PFS, but on-treatment loss of T790M did not. Emergent genetic alterations postprogression included C797S, MET amplification, and EGFR amplification. CONCLUSIONS: .
SDGs
Publisher
American Association for Cancer Research Inc.
Type
journal article