A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors
Byoung Chul Cho, Ji-Youn Han, Sang-We Kim, Ki Hyeong Lee, Eun Kyung Cho, Yun-Gyoo Lee, Dong-Wan Kim, Joo-Hang Kim, Gyeong-Won Lee, Jong-Seok Lee, Byoung Yong Shim, Jin-Soo Kim, Sang Hoon Chun, Sung Sook Lee, Hye Ryun Kim, Min Hee Hong, Jin Seok Ahn, Jong-Mu Sun, Youngjoo Lee, Dae Ho Lee, Ji Ah Kang, NaMi Lee, Mi-Jung Kwon, Carin Espenschied, Arielle Yablonovitch, Myung-Ju Ahn, Byoung Chul Cho, Ji-Youn Han, Sang-We Kim, Ki Hyeong Lee, Eun Kyung Cho, Yun-Gyoo Lee, Dong-Wan Kim, Joo-Hang Kim, Gyeong-Won Lee, Jong-Seok Lee, Byoung Yong Shim, Jin-Soo Kim, Sang Hoon Chun, Sung Sook Lee, Hye Ryun Kim, Min Hee Hong, Jin Seok Ahn, Jong-Mu Sun, Youngjoo Lee, Dae Ho Lee, Ji Ah Kang, NaMi Lee, Mi-Jung Kwon, Carin Espenschied, Arielle Yablonovitch, Myung-Ju Ahn
Abstract
Introduction: This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy.
Methods: Adults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR.
Results: A total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1-66.4). Median progression-free survival was 11.1 months (95% CI: 5.5-16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%-100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss.
Conclusions: Lazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy.
Keywords: EGFR T790M-positive non-small cell lung cancer (NSCLC); Epidermal growth factor receptor (EGFR); Lazertinib; Tyrosine kinase inhibitor (TKI).
Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Source: PubMed