A Phase 1/2 Study of Lazertinib 240 mg in Patients with Advanced EGFR T790M-Positive Non-Small Cell Lung Cancer After Prior EGFR Tyrosine Kinase Inhibitors.

This integrated analysis of a phase 1/2 study (NCT03046992) assessed 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 prior EGFR TKI therapy.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.Seventy-eight patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (n=76), 1 (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% 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 months). In patients with measurable intracranial lesions (n=7), 1 (14.3%) had a complete intracranial response and 5 (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 3 patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss.Lazertinib 240 mg/day has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after prior EGFR TKI therapy.