Abstract
IntroductionThis 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. MethodsAdults 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. ResultsA 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. ConclusionsLazertinib 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.
Highlights
This integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive non-small cell lung cancer (NSCLC) after previous EGFR tyrosine kinase inhibitors (TKIs) therapy
We focus on the 240 mg dose of lazertinib, which is currently being investigated in phase 3 trials and has recently been approved for use in South Korea.[9]
EGFR T790M was detected by central confirmation at baseline in 76 patients (97.4%)
Summary
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. Lazertinib (YH25448, JNJ-73841937) is a potent, irreversible, brain-penetrant, mutant-selective, but wildtype–sparing, third-generation EGFR TKI.[7] In preclinical studies, lazertinib had improved activity compared with osimertinib in EGFR single- and double-mutant patient-. Lazertinib in Advanced EGFR T790MD NSCLC 3 derived cell lines and good blood-brain barrier penetration and antitumor activity in a brain metastasis model.[7] In a first-in-human phase 1/2 study (LASER201), lazertinib had promising clinical activity and a manageable safety profile in patients with advanced EGFR mutation-positive NSCLC who had previously received EGFR TKIs.[8]
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